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IHP OCTOBER 2012 | $14.95

Urinary neurotransmitter testing

Novel lipid markers of CVD risk

Male Fertility

By Tara Campbell, ND

By Chris Habib, ND and Philip Rouchotas, MSc, ND

By Elizabeth Cherevaty, ND

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Continuing Education

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Introducing the Journal of IHP

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from the publisher

Connect With Us

Transformation

A

s many of you are aware our new editorial and peer review boards are in place. With their input and guidance you will see many changes to IHP aimed at helping us better deliver content in a way that separates news, stories, and profiles from peer- reviewed feature articles. We are pleased and honoured to have the editorial board working with us. Moving forward you will see IHP develop a strong online presence, with an e-newsletter and an online forum currently in the pipeline. Please drop by at our OAND booth and let us know your thoughts on the changes.

Sanjiv Jagota Publisher

from the editor

Here we grow again!

A

s per the guidance of our recently formed Editorial Board, IHP has separated peer- reviewed content from stories/news/profiles... We have made these changes in an effort to showcase the heightened level of academic rigor that goes into the assimilation and peer review of feature articles and continuing education articles presented within IHP. The continued advancement of this publication is made possible through the generous donation of time and expertise of our submitting authors, our peer reviewers, and the esteemed members of our editorial board. We remain committed to the advancement of clinical practice in the realm of integrative medicine, and welcome comments or suggestions as to how we can continue to improve upon the delivery of Integrated Healthcare Practitioners.

Philip Rouchotas, MSc, ND Editor-in-Chief

4 www.ihpmagazine.com l October 2012

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Calendula Calendula Vitamin E Cream Vitamin E Cream

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By Terry Vanderheyden, ND

Wound Healer

Wound Healer

Calendula stands out as our premier herb for the healing and nourishment of the skin. It is also our best wound-healer. Think of Calendula Vitamin E Cream for skin ulcers and slow-healing wounds, as well as burns and scalds (Hoffmann 2003).

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Anti-inflammatory Calendula is a potent anti-inflammatory (Yarnell 2004). It is this one-two action that sets calendula apart from other dermatological agents: its wound-healing and inflammation-quenching properties make it ideal for healing the skin.

Chicken Pox

Terry Vanderheyden, ND Research Consultant

Lesley Tierra (2003) states that calendula is specific for the beginning stages of measles, rashes, and other eruptive diseases. She adds that, “When my son had the chicken pox, I only had to apply calendula tincture once to each pox for the itching and eruption to stop”.

Bacteriostatic

References:

1. David Hoffmann, Medical Herbalism, Rochester, VT: Healing Arts Press, 2003, p. 559. 2. SM Lavagna et al. “Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section.” Il Farmaco 2001; 56: 365-371. 3. Eric Yarnell, “Compendium of Pharmacological American folk herbalist Matthew Wood contends that externally used calendula has a specific affinity Actions of Medicinal Plants and Their for swollen, hot, painful, and pus-fi lled tissue (Wood 1997). In the authoritative expandedConstituents”, edition of©the Used topically to aid in healing abrasions, bedsores, 2004Commission Eric Yarnell, ND,ERH. monographs, herbal researcher Mark his cracked heels, chapped hands, cuts, varicose veins, 4. Lesley Tierra,Blumenthal Healing with theand Herbs of Life, Scar Prevention Thecontemporary Crossing Press; 2003. fellow editors point out that, Toronto: “In both and venous congestion, and surface wounds, our Calendula Wood (1997) addsofthat the use of calendula immediately after an injury prevents the formation of 5. David Hoff mann, Medical Herbalism, Rochester, historic times, Calendula tinctures, ointments, and washes Cream is one a trio of topical products that feature “unsightly scar tissue”. Wood relates a case from the literature where a woman was upset about the VT: Healing Arts Press, 2003, p. 559. have been used to notably speed the healing of burns, Calendula flower, a herb with the most convincing 6. Edmund Carleton, Homeopathy in Medicine and potential of being disfigured from a serious wound to the nose: “Calendula was applied, and the healing bruises, cuts, and the minor infections that they cause. ” 1913. credentials when it comes to dealing with skin problems. Surgery, Philadelphia: Boericke & Tafel; of the wounds was so perfect that no one would suspect that there has ever been a wound of any kind.” In this case, the Certified Organically Grown Calendula 7. Shute, Vogelsang, Skelton and Shute 1948 Surg., “Small wonder, herbal Vitamin E furthermore prevents scarwith contraction as wounds heal (Shute, Vogelsang, Skelton and” notes the prominent Gyn. and Obst. 86:1. botanist James flowering tops are combined other supportive herbs Duke, “that this pretty flower has a folk reputation treating Shute 1948). Vitamin E also occasionally lyses scar tissue (Steinberg 1948). 8. Steinberg (1948) Med. Clin. N.for America 30:221, and highlighted by the addition of Vitamin E, which plays 1946. all kinds of skin problems. Research shows that this herb a signal role as an antioxidant, helping to stabilize and repair Matthew Wood, The Book Herbal Wisdom, Lymphatic is antibacterial, antifungal,9.anti-inflammatory andofantiviral. cell membranes. All these ingredients are then infused in Berkeley, CA: North Atlantic Books; 1997. Calendula is also a premier used both orally and Calendula also stimulates white blood cells to gobble up extra-virgin Olive Oil. lymphatic alterative (Yarnell 2004) and as such can be 10. Evan Shute, The Vitamin E Story, Burlington, topically to relieve swellings, whether from glandular affections or trauma. Wood adds that it is this and helps speed wound healing.” harmful microbes Ontario: Welch Publishing; 1985.

Calendula is bacteriostatic and hemostatic. The surgeon and homeopath Edmond Carleton, MD, esteemed calendula so highly as an aid to prevent sepsis from surgery and for speeding wound healing that he wrote, “I would almost as soon leave my instruments at home when going to cut as my succus calendulae…” (Carleton 1913). Carleton explains that calendula is homeopathic to clean wounds. In other words, it is bacteriostatic.

lymphatic effect that helpswell-respected resolve wounds with no outlet, by draining Commission E, the regulatory body thatinfection via the lymphatic system.

Blumenthal and his colleagues add significantly that, “Tests also demonstrate that ointments containing London Ontario doctor Evan Shute wrote extensively about vitamin E, and he and his brother Calendula activate tissue regeneration and epithelial of the oral and pharyngeal mucosa. It was also approved Wilfred were pioneers of its use for heart disease. They contend that vitamin E tissue is exceeded by no development. ” externally for poorly healing wounds.” oversees herbal medicines in Germany, “approved the

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Publisher | Sanjiv Jagota (416) 203-7900 ext 6125 Editor-in-Chief | Philip Rouchotas, MSc, ND (416) 203-7900 ext. 6109 Associate Editor | Angela MacNeil, MSc, ND Art Director | Scott Jordan Design | Sarah Vincett Production | Erin Booth (416) 203-7900 ext. 6110 Contributors Angela MacNeil, MSc, ND Christopher Habib, ND Philip Rouchotas, MSc, ND Heidi Fritz, MA, ND Tara Campbell, ND Elizabeth Cherevaty, ND

President | Olivier Felicio (416) 203-7900 ext. 6107 Vice President Operations | Frank Shoniker (416) 203-7900 ext. 6109 Controller & Operations | Melanie Seth (416) 203-7900 ext. 6114 Finance Administrator | Henry Fonseca (416) 203-7900 ext. 6127 Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Paul Airut | Tel: (416) 203-7900 ext 6103 Email: paul@gorgmgo.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com Erin Poredos | Tel: (416) 203-7900 ext 6128 Email: erin@gorgmgo.com

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Published by Canada Post Canadian Publication Mail Agreement Number 4067800 The publisher does not assume any responsibility for the contents of any advertisement and any and all representations or warranties made in such advertising are those of the advertiser and not of the publisher. The publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the publisher’s liability shall not exceed the amount of the publisher’s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the publisher. ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for editorial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their affiliates for editorial purposes in any media (whether printed, electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such material. Please direct submissions to the Editor, ihp magazine.

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contents

This Issue: October 2012 • Vol. 5 • No. 5

33 Dr Kristy Prouse, MD, FRCSC Cover Story

Institute for Hormonal Health

Clinic Profile

41 Mahaya Forest Hill Integrative Clinic

Clinic Director Christopher Habib, ND

45 The Journal of IHP

Peer-reviewed articles on clinically revelant topics

Coming Next Issue ➜ Salvestrols; novel anti cancer agent ➜ Strategies for enhancing women’s fertility ➜ Localized hyperthermia in cancer management

Departments

4 Publisher’s Letter 11 Research News 18 Industry News 25 Calendar 26 Product Profiles 46 Editor’s Letter 49 Peer Review Board 51 Editorial Board 71 Intravenous Continuing Education: Therapies

Fish oil based lipid emulsions (FOBLE)

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METAGENICS NUTRAGEMS COQ10 300 NutraGems by Metagenics features chewable gels containing advanced, emulsified Coenzyme Q10 (CoQ10) designed to provide general support for cardiovascular health, energy production, antioxidant protection, and overall wellness and healthy aging. CoQ10, also known as ubiquinone, is a fat-soluble substance present in most human cells, with the highest concentrations in the heart, liver, kidney, and pancreas (Aberg 1992). CoQ10 is synthesized in the human body and is also obtained from the diet. Meat, fish, nuts, and some oils are the main dietary sources of CoQ10 (Pravst 2010). CoQ10 is an essential cofactor in the synthesis of mitochondrial adenosine triphosphate (ATP) and therefore a key component of the mitochondrial respiratory chain (Ernster 1995). Since most cellular functions depend on adequate supply of ATP, CoQ10 is essential for the health of virtually all tissues and organs. CoQ10 as the reduced form is also an antioxidant, protecting membranes from oxidation (Mellors 1966), inhibiting the peroxidation of lipoprotein lipids (Stocker 1991), and may also have a role in regenerating other antioxidants such as vitamin E (Sohal 2004). Due to its lipophilicity and high molecular weight, CoQ10 from oral supplementation is absorbed slowly from the gastrointestinal tract; the uptake mechanism is similar to that of vitamin E. Depending on the delivery forms of CoQ10, the Tmax is approximately 6 – 8 h (Bhagavan 2006). CoQ10 is transported via the lymphatics to the circulation (Katayama 1972). The majority of CoQ10 is eliminated via biliary and fecal excretion. The elimination half-life is approximately 33 – 34 h (Tomono 1986; Greenberg 1990). Genetic CoQ10 deficiencies can occur as a result of defects of ubiquinone biosynthesis (primary deficiencies) or due to other causes (secondary deficiencies); major clinical phenotypes include encephalomyopathy, severe infantile multisystemic disease, cerebellar ataxia, isolated myopathy, and nephritic syndrome (Quinzii 2011). Various studies have shown that oral administration of CoQ10 improves signs and symptoms associated with CoQ10 deficiencies (Quinzii 2011). Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors, or statins, inhibit the synthesis of cholesterol by inhibiting mevalonate, a main precursor of both cholesterol and CoQ10. Studies have shown that statin therapy reduced serum and muscle CoQ10 levels (Folkers 1990; Ghirlanda 1993; Watts 1993; Paiva 2005). It has been hypothesized that mitochondrial dysfunction through depletion of CoQ10 is one underlying pathophysiology of statin-induced myopathy (Thompson 2003). Preliminary clinical trials have found CoQ10 prevent or improve statin-associated myalgic symptoms (Thibault 1996; Kim 2001; Caso 2007). Because of its bioenergetic role and antioxidant properties, CoQ10 has been investigated in numerous studies for its potential benefit for cardiovascular health. A recent meta-analysis based on 12 clinical trials found that CoQ10 had the potential to lower systolic and diastolic blood pressure in hypertensive patients (Rosenfeldt 2007); this effect is likely related to the improvement in endothelial function (Tiano 2007). Myocardial depletion of CoQ10 has been observed in heart failure and the severity of symptoms is associated with the severity of CoQ10 deficiency (Folkers 1985). At least 2 meta-analyses investigating CoQ10 supplementation in chronic heart failure reported improvement in stroke volume, ejection fraction, cardiac output, cardiac index, or end diastolic volume index (Soja 1997; Sander 2006). CoQ10 may be valuable as an adjunctive clinical therapy of cardiovascular disease (Greenberg 1990; Langsjoen 1999; Molyneux 2008). Health Canada Natural Health Product monograph states that CoQ10 helps maintain and/or support cardiovascular health (HealthCanada 2007). Two clinical studies found that CoQ10 supplementation may be efficacious in preventing migraine headaches (Rozen 2002; Sandor 2005). One larger study found that CoQ10 deficiency may be common in pediatric and adolescent migraine, and CoQ10 supplementation may result in clinical improvement (Hershey 2007). Health Canada Natural Health Product monograph states that CoQ10 helps reduce the frequency of migraine headaches and associated nausea and vomiting when taken as a prophylactic (HealthCanada 2007). Mitochondrial respiratory chain dysfunction and oxidative stress are key features of some neurodegenerative disorders. Preliminary data from pilot clinical trials of high-dose CoQ10 for early-stage patients showed some potential benefit of CoQ10 in improving motor function, slowing progression, and improving some clinical symptoms (Beal 2002; Shults 2002; Horstink 2003). Large-scale controlled trials investigating CoQ10 and neurodegenerative health are currently underway. Preliminary data also found that CoQ10 may improve semen quality, sperm count, or sperm motility in infertile men with idiopathic oligoasthenoteratospermia (Balercia 2009; Safarinejad 2009). There are other preliminary data indicating a potential benefit of CoQ10 in several other indications (Littarru 2010). CoQ10 has an excellent safety record. It is well tolerated, with few potential drug interactions. Only minor adverse effects such as gastrointestinal upset and headache were reported (Rosenfeldt 2007). NutraGems CoQ10 300 ingredients (per 1 chewable gel) Ingredient Dose Unit Calories 5 kcal Sugar alcohol 0.5 g Coenzyme Q10 300 mg

References

Aberg, F., E. L. Appelkvist, et al. (1992). Arch Biochem Biophys 295(2): 230-4. Balercia, G., E. Buldreghini, et al. (2009). Fertil Steril 91(5): 1785-92. Beal, M. F. (2002). Free Radic Res 36(4): 455-60. Bhagavan, H. N. and R. K. Chopra (2006). Free Radic Res 40(5): 445-53. Caso, G., P. Kelly, et al. (2007). Am J Cardiol 99(10): 1409-12. Ernster, L. and G. Dallner (1995). Biochim Biophys Acta 1271(1): 195-204. Folkers, K., P. Langsjoen, et al. (1990). Proc Natl Acad Sci U S A 87(22): 8931-4. Folkers, K., S. Vadhanavikit, et al. (1985). Proc Natl Acad Sci U S A 82(3): 901-4. Ghirlanda, G., A. Oradei, et al. (1993). J Clin Pharmacol 33(3): 226-9. Greenberg, S. and W. H. Frishman (1990). J Clin Pharmacol 30(7): 596-608. HealthCanada. (2007). "Natural Health Product Monographs: Coenzyme Q10." Retrieved March 5, 2012,

IHPJUN2012_Metagenics_CoQ10_9316_FP2.indd 2

from http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licenprod/monograph/mono_coenz-q10-eng.php. Hershey, A. D., S. W. Powers, et al. (2007). Headache 47(1): 73-80. Horstink, M. W. and B. G. van Engelen (2003). Arch Neurol 60(8): 1170-2; author reply 1172-3. Katayama, K. and T. Fujita (1972). Chem Pharm Bull (Tokyo) 20(12): 2585-92. Kim, W. S., M. M. Kim, et al. (2001). Invest New Drugs 19(1): 81-3. Langsjoen, P. H. and A. M. Langsjoen (1999). Biofactors 9(2-4): 273-84. Littarru, G. P. and L. Tiano (2010). Nutrition 26(3): 250-4. Mellors, A. and A. L. Tappel (1966). J Biol Chem 241(19): 4353-6. Molyneux, S. L., J. M. Young, et al. (2008). Clin Biochem Rev 29(2): 71-82. Paiva, H., K. M. Thelen, et al. (2005). Clin Pharmacol Ther 78(1): 60-8. Pravst, I., K. Zmitek, et al. (2010). Crit Rev Food Sci Nutr 50(4): 269-80. Quinzii, C. M. and M. Hirano (2011). Biofactors 37(5): 361-5. Rosenfeldt, F. L., S. J. Haas, et al. (2007). J Hum Hypertens 21(4): 297-306. Rozen, T. D., M. L. Oshinsky, et al. (2002). Cephalalgia 22(2): 137-41. Safarinejad, M. R. (2009). J Urol 182(1): 237-48. Sander, S., C. I. Coleman, et al. (2006). J Card Fail 12(6): 464-72. Sandor, P. S., L. Di Clemente, et al. (2005). Neurology 64(4): 713-5. Shults, C. W., D. Oakes, et al. (2002). Arch Neurol 59(10): 1541-50. Sohal, R. S. (2004). Methods Enzymol 378: 146-51. Soja, A. M. and S. A. Mortensen (1997). Mol Aspects Med 18 Suppl: S159-68. Stocker, R., V. W. Bowry, et al. (1991). Proc Natl Acad Sci U S A 88(5): 164650. Thibault, A., D. Samid, et al. (1996). Clin Cancer Res 2(3): 483-91. Thompson, P. D., P. Clarkson, et al. (2003). JAMA 289(13): 1681-90. Tiano, L., R. Belardinelli, et al. (2007). Eur Heart J 28(18): 2249-55. Tomono, Y., J. Hasegawa, et al. (1986). Int J Clin Pharmacol Ther Toxicol 24(10): 536-41. Watts, G. F., C. Castelluccio, et al. (1993). J Clin Pathol 46(11): 1055-7.

12-10-03 1:21 PM


research news Erythrocyte folate concentrations reached steady-state within one year of supplementation

Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH The aim of this placebo-controlled crossover study was to evaluate the influence of inulin on iron absorption, bifidobacteria, total bacteria, shortchain fatty acids (SCFAs), and fecal pH in women with low iron status (plasma ferritin <25 μg/L). Thirty-two subjects consumed inulin or placebo three times daily (~20 g/d) for four weeks, separated by a two-week washout period. After three weeks of inulin and placebo consumption, mean fractional iron absorption from a standard test meal in the inulin (15.2%; 95% CI 8.0-28.9) and placebo (13.3%; 95% CI 8.1-24.3)

periods did not differ significantly (P = 0.10). Inulin decreased fecal pH (P < 0.001) and increased fecal bifidobacteria (P < 0.001) and fecal lactate (P < 0.001). It had no effect on fecal SCFAs or total bacteria. Changes in lactate and acetate concentrations were positively correlated with changes in propionate (P < 0.001) and butyrate (P < 0.02) concentrations, respectively. Iron absorption correlated with fecal pH in the placebo period (P < 0.01) but not in the inulin period (P = 0.37). Therefore, although inulin has prebiotic activity, no increases in iron absorption were found in women with low iron status. Am J Clin Nutr. 2012 Jun 27. PMID: 22743314

Preoperative sex steroids are significant predictors of early biochemical recurrence after radical prostatectomy This study investigated the association of preoperative serum total testosterone (tT), hypogonadism, 17β estradiol (E2), and sex hormone-binding globulin (SHBG) with early biochemical recurrence after radical prostatectomy [defined as a prostate specific antigen (PSA) ≥ 0.1 ng/ml occurring within 24 months after radical prostatectomy]. Sex steroids were assessed the day before surgery (7-11 a.m.) in a cohort of 605 patients. Early biochemical recurrence was found in 5.6 % of patients. Compared to those without biochemical recurrence, patients with recurrence did not differ in terms of age, BMI, serum PSA, tT, E2, and SHBG levels, rate of hypogonadism, and clinical stage (all P ≥ 0.05). Conversely, patients with biochemical recurrence showed a greater prevalence of biopsy Gleason scores ≥4 + 3 (all P ≥ 0.001). Multivariable regression analysis revealed that tT (p = 0.03), E2 (P = 0.04), SHBG (P = 0.02), and biopsy Gleason scores equal to 4 + 3 (P = 0.04) and ≥8 (P < 0.001) achieved independent predictor status for early biochemical recurrence. These findings show that preoperative serum sex steroids are independent predictors of early biochemical recurrence in a large cohort of patients treated with radical prostatectomy. World J Urol. 2012 Mar 24. PMID: 22441310

The time for daily supplementation with folate to reach steady-state concentrations has not been empirically demonstrated. This two-year, doubleblind, placebo-controlled, randomized trial involving 276 participants aged ≥65 years sought to determine the time to steady-state erythrocyte folate concentrations following the initiation

of daily supplementation with 1 mg folate. Erythrocyte folate concentrations were measured at baseline and at 6, 12, 18, and 24 months. The mean plasma and erythrocyte folate concentrations in the folate-supplemented group were higher compared to the placebo group at 6, 12, 18, and 24 months (P < 0.001). The difference in erythrocyte folate concentrations between the folate and placebo group at six months was 1.78 μmol/L (95% CI 1.62-1.95) after adjusting for baseline differences. This difference increased significantly to 2.02 μmol/L (95% CI 1.85-2.18) at 12 months but did not significantly change after the next year of folate supplementation; for example, erythrocyte folate concentration was 2.09 μmol/L (95% CI 1.92-2.27) and 1.98 μmol/L (95% CI 1.18-2.15) at 18 and 24 months, respectively. Therefore, 12 months of daily folate supplementation with 1 mg is sufficient to cause erythrocyte folate concentrations to reach a new steady state. J Nutr. 2012 Jul 18. PMID: 22810981

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research news Agreement between DSM-IV and DSM-V attention deficit hyperactivity disorder diagnostic criteria No empirical data exists regarding the American Psychiatry Associationâ&#x20AC;&#x2122;s proposed new diagnostic criteria for attention deficit hyperactivity disorder (ADHD). This study was conducted to examine the agreement between ADHD diagnosis derived from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and DSM-V diagnostic criteria; it also reports sensitivity, specificity, and agreement for ADHD diagnosis. Children and adolescents (N = 246) were interviewed face to face by a clinician using ADHD diagnostic criteria for both DSM-V and DSM-IV. The rate of ADHD diagnosis using DSM-V was significantly higher than the rate detected using DSM-IV diagnostic criteria. The sensitivity of DSM-V diagnostic criteria was 100%, while its specificity was 71.1%. The kappa agreement between DSM-IV and DSM-V was 0.75. In addition, positive predictive value was 85.1%. Although all four newly added symptoms to ADHD diagnostic criteria were statistically more common in the ADHD group than the comparison group, these symptoms were very common in the children without ADHD. The authors suggest that the rate of ADHD diagnosis will increase using the proposed ADHD DSM-V criteria and that the newly added symptoms have a low specificity for ADHD diagnosis. Compr Psychiatry. 2012 Jul 16. PMID: 22809622

Fast eating may increase the risk of type 2 diabetes mellitus This case-control study was conducted to assess the relationship between eating speed and the risk of type 2 diabetes mellitus; subjects included 234 cases with newly diagnosed type 2 diabetes and 468 non-diabetic controls. A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes. The speed of eating was self-reported by study subjects compared to other subjects, with whom they were eating at the same table. The OR and 95% CI for type 2 diabetes were calculated by a conditional logistic regression. Variables such as a

family history of diabetes, body mass index, waist circumference, educational level, morning exercise, smoking, and plasma triglycerides level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the OR by more than 5% in any exposure category. After adjustment for possible confounders, subjects who ate faster had more than a two-fold increased risk of type 2 diabetes (OR = 2.52; 95% CI 1.56-4.06) compared to subjects who ate more slowly. This result supports a possible relationship between faster eating speed and the increased risk of type 2 diabetes mellitus. Clin Nutr. 2012 Jul 14. PMID: 22800734

Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: meta-analysis

This meta-analysis of randomized controlled trials was conducted to evaluate the effect of angiotensin converting enzyme inhibitors (ACEI) on the development of new-onset type 2 diabetes. Trials were identified by electronic and manual searches and nine trials with 92,404 patients (72,128 non-diabetic patients at baseline) were included for analysis. Incidence of new-onset diabetes was significantly reduced in the ACEI group (OR 0.80; 95% CI 0.71-0.91) compared to the control group and this was irrespective of achieved blood pressure levels at follow-up. ACEI therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics (OR 0.78; 95% CI 0.65-0.93), placebo (OR 0.79; 95% CI 0.64-0.96), or calcium channel blockers (OR 0.85; 95% CI 0.73-0.99). ACEI treatment was also associated with a significant reduction in the risk of new-onset diabetes in patients with hypertension (OR 0.80; 95% CI 0.68-0.93), coronary artery disease or cardiovascular disease (OR 0.83; 95% CI 0.68-1.00), and heart failure (OR 0.22; 95% CI 0.10-0.47). Therefore, ACEIs have beneficial effects in preventing new-onset diabetes and lowering the risk of new-onset diabetes in patients with hypertension, coronary artery disease, and other cardiovascular disease. Int J Cardiol. 2012 Jul 16. PMID: 22809536

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Product MonograPh Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. Without treatment, AGA is progressive, and causes social distress in many affected men and women (Sinclair 1998). Bio-Fen Plus contains extracts DESCRIPTION of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme Vitaline® CoQ10 tablets containare coenzyme Q10for formulated Micosolle®, a proprietary excipient.1 Clinical studies have demonstrated that this 5α-reductase. These inhibitors responsible relieving with symptoms associated with hereditary AGA. process the absorption of CoQ10.2-4 One ofenhances the primary causes of hair loss is a high level of the male hormone dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001). For people with AGA, their follicles have a greater number of androgen receptors to which DHT attaches. 5-α-reductase catalyzes the enzymatic Two differentofmethods can be for the productionwhich of coenzyme One method is natural thethan otherthe is synthetic. The natural process1998). utilizes conversion testosterone to used dihydrotestosterone, binds toQ10. the receptor five-fold moreand avidly parent compound (Sinclair living organisms and is referred to as a “biological fermentation/extraction process.” Coenzyme Q10 can also be synthesized by a chemical process, which Vitamins Saw palmetto (Serenoa produces a similar, butrepens) distinctly different product that contains chemical compounds not found in the natural form. Vitaline® CoQ10 contains the Standardized Serenoa natural form (lipophillic) of coenzyme Q10.1extract has been found to be a potent inhibitor In a Polish study of 46 women who had symptoms of diffuse alopecia, calcium of 5α-reductase, resulting in decreased tissue DHT. An open-label, dose response study was conducted on 42 healthy males to determine the effect of a combination

pantothenate was orally administered twice a day in doses of 100 mg for four to five months, and vitamin B6 was injected every day for 20 to 30 days and repeated

STRUCTURE/FUNCTION/USAGE again after six months (Brzezińska-Wcisło 2001). It was determined that vitamin of carotenoid astaxanthin and saw palmetto berry lipid extract on DHT and Vitaline® is a dietary2008). supplement to enhance cellular of CoQ10, with subsequent of CoQ10 affected physical B6 administered parenterally for a support few weeks induces improvement in the hair testosteroneCoQ10 levels (Angwafor The men were divided intomitochondrial two groups: levels systems, of cardiac, neurological,supplement and immune condition in a subset of women and reduces hair loss. one groupincluding received support 800 mg/day of the combination andhealth.* the other group received 2000 mg/day of the supplement for 14 days. ANOVA-RM showed significant within-group increases in serum total testeosterone and significant FORMULA Medicinal Ingredients decreases serum DHT strengths from baseline in both dose groups (P=0.05). There There are in three available of Vitaline® CoQ10 tablets. was no significant difference between dose groups with regard to the increase of Fenugreek (Trigonella foenum graecum) One 25 mg chewable waferofcontains: testeosterone or the decrease DHT; therefore both doses were effective (Angwafor seed extract 4:1mg Coenzyme Q10 (CoQ10) (ubiquinone)…………………………………………...………….25 2008). One 60 mg chewable wafer contains: Saw palmetto berry extract containing Another study liposterolic extract of Serenoa repens (LSESr) and betaCoenzyme Q10tested (CoQ10) (ubiquinone)…………………………………………...………….60 mg 45% free fatty acids sitosterol thechewable treatmentwafer of males (23-64 years of age) with mild to moderate AGA. One 200inmg contains: Flax lignans, standardized to 20% Six of 10 (60%) were(ubiquinone)…………………………………………………….200mg rated as improved at the final visit, thus establishing Coenzyme Q10subjects (CoQ10) secoisolariciresinol diglucoside (SDG) the effectiveness of 5α-reductase inhibitors against AGA (Prager 2002). Chronic Vitaline® Chewable formulated a proprietary process thatAenhances the absorption of CoQ10. inflammation of the hairCoQ10 follicle isisconsidered to with be a contributing factor for AGA. study by Chittur et al sought to determine whether blockade of inflammation using

D-calcium pantothenate (Vitamin B5)

dose Per capsule 260 mg 160 mg

100 mg 10.40 mg

RECOMMENDATIONS LSESr and two anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg theaexpression of molecular take markers inflammation 2009). was found or health care professional. Refer to label for complete instructions. As dietary supplement, 1-2oftablets daily or (Chittur as directed by aIt physician that the combination suppressed lipopolysaccharide-activated gene expression of

Pyridoxine HCl (Vitamin B6)

2 mg

chemokines associated with pathways involved in inflammation and apoptosis. PRECAUTIONS Riboflavin (Vitamin B2) 1.58 mg The study concluded that 5-alpha reductase inhibitors in combination with The safetyofof CoQ10 hasprocesses been evaluated. Dosages in studies have ranged from 100 mg every day to 1200 mg per day. To date, no toxicities have been blockade inflammatory could represent a new two-pronged approach Folic acid 0.095 mg reported. Occasional gastric upset may occur.12, 13 Taking Vitaline® CoQ10 wafers with meals usually alleviates this rare upset.1 in the treatment of AGA.

Biotin

Fenugreek Seeds STORAGE RECOMMENDATIONS Fenugreek seeds contain to 30% protein, steroid sterols, flavonoids Store at controlled room5% temperature, 59° to 86°Fsaponins, (15° to 30°C).

and alkaloids (notably trigonelline and choline). Steroid saponins bind and eliminate extra cholesterol and hormones in the body; DHT is made from testosterone, which is in turn is made from cholesterol. Therefore, when excess cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for References one month, higher levels of consumption resulted in a significant reduction in total 1. Meese J. President. Vitaline® Corporation. Personal communication (verbal). October 20, 2000. cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999).

400 mcg

non-Medicinal Ingredients Inert microcrystalline cellulose and vegetable-based magnesium stearate in a veggie-based capsule Recommended adult dose: One capsule per day

2. Nakmura T, Sanma M, Himeno M, Kato K. Transfer of exogenous coenzyme Q10 to the inner membrane of heart mitochondria in rats. In: Folkers K, Yamamura Y, eds. Biomedical and Clinical Aspects of Coenzyme Q. Vol 6. Amsterdam: Elsevier Press; 1980;3-14.

Flax lignans Flax reduces the amount of DHT produced by reducing cholesterol levels in the 4. Joliet P, Simon N, Barre J, et al. Plasma coenzyme Q 10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther. 1998;36:506-509. body. A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed 5. Mitchell P. The reduces vital protonmotive of coenzyme In: Folkers K, Littarru GP, Yamagami T. Eds. Biochemical significantly circulating totalQ.and LDL-cholesterol concentrations (Pan and Clinical Aspects of Coenzyme Q. Vol 6. Amsterdam: Elsevier Press; 1991:3-10. 6. Sinatra ST, DeMarcointerventions J. Free radicals, oxidative stress, oxidized density lipoprotein (LDL) and the heart: antioxidants and other strategies to limit cardiovascular damage. Conn Med. 1995;59:579-588. 2009). Flaxseed reduced total andlow LDL cholesterol by 0.10 mmol/L (95% CI: 0.00 F,mmol/L) 0.08 mmol/L (95% -0.16, function 0.00 mmol/L), 7. Ravaglia G, -0.20, Forti P, Maioli et al. Effect and of micronutrients on natural killerCI: cell immune in healthy free-living subjects aged >/=90y. Am J Clin Nutr. 2000:71:590-598. respectively. Significant reductions were with whole (-0.21 and of these compounds in rat tissues and mitochondria. J Nutr. 2000;130:2434-2438. 8. Ibrahim WH, Bhagahav HN, Chopra RK, Chow CK.observed Dietary coenzyme Q10 andflaxseed vitamin E alter the status -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) 9. Porth CM, Carroll EW. Mitochondria. In: Porth CM. Pathophysiology: Concepts of Altered Health States. 5th ed. Philadelphia, Pa; Lippincott; 1998:8-9. supplements (Pan 2009). 3. Matthews RT, Yang L, Browne S, Baik MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci USA. 1998;95:8892-8897.

10. Guyton AC, Hall JE. Mitochondria. In: Textbook of Medical Physiology. 9th ed. Philadelphia, Pa: WB Saunders; 1996:16-17.

11. Langsjoen PH, Langsjoen A, Willis R, Folkers K. Treatment of hypertrophic cardiomyopathy with coenzyme Q10. Mol Aspects Med. 1997;18 Suppl:S145-S151 12. Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects References Med. 1994;15 Suppl:S287-294. Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J IntSacher Soc Sports NutrML, 2008;5:12. 13. HL, Sacher Landau SW, et al. The clinical and hemodynamic effects of coenzyme Q10 in congestive cardiomyopathy. Am J Ther. 1997;4:66-72. 14. Kim Y, Sawada Y, Fujiwara G, ChibaofH,vitamin Nishimura Therapeutic of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123aspects labeled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acidWiad myocarBrzezińska-Wcisło L. Evaluation B6T. and calcium effect pantothenate effectiveness on hair growth from clinical and trichographic for treatment of diffuse alopecia in women. dial emission tomography. Eur J Nucl Med. 1997;24:629-634. Leksingle-photon 2001;54:11-8. 15. Littarru Lippa S, Oradei A,G. Fiorni RM, Mazzanti L. Metabolic gene and diagnostic implications of blood CoQ10 In: Folkers K, Littarru GP, Yamagamithioctic T. Eds Biomedical Aspects of Coenzyme Q. Vol 6. Chittur S,GP, Parr B, Marcovici Inhibition of inflammatory expression in keratinocytes using levels. a composition containing carnitine, acid andand sawClinical palmetto extract. Evid Based Amsterdam: Elsevier Press; 1991:167-180. Complement Alternat Med 2009. 16. Carroll EW, Curtis RL. Blood-brain barrier. In: Porth CM. Pathophysiology: Concepts of Altered Health States.5th ed. Philadelphia, Pa; Lippincott; 1998:869. Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97. 17. Flaherty JF. Blood-brain barrier. In: Young, LY, Koda-Kimble MA. Applied Therapeutics: The Clinical Use of Drugs. 6th ed. Vancouver, Wash: Applied Therapeutics, Inc; 1995: chapter 56, page 2. Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med 2002;8:143-52. Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9. Sinclair R. Male pattern androgenetic alopecia. BMJ 1998;317:865-9. Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87. Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

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research news Caffeine improves motor measures in patients with Parkinson disease

Lactobacillus reuteri DSM 17938 effectively treats acute diarrhea in children Probiotics seem to be efficacious for the management of acute diarrhea but the effect is strain specific. This randomized, double-blind trial was conducted to investigate the efficacy and safety of Lactobacillus reuteri DSM 17938 derived from L. reuteri ATCC 55730 (dose of 4 × 10(8) colony-forming units/die) in children with acute diarrhea. Subjects included children (6-36 months; N = 69) who had been hospitalized with acute diarrhea and had clinical signs of dehydration. Lactobacillus reuteri significantly

reduced the duration of watery diarrhea compared to placebo (2.1 ± 1.7 days vs. 3.3 ± 2.1 days; P < 0.03). On day two and three of treatment, watery diarrhea persisted in 82% and 74% of the placebo group, and 55% and 45% of the treatment group, respectively (P < 0.01; P < 0.03). Finally, the L. reuteri group had a significantly lower relapse rate of diarrhea (15% vs. 42%; P < 0.03) although no significant differences in hospital stay were noted between the groups. This study revealed that L . reuteri DSM 17938 as an adjunct to rehydration therapy is efficacious and safe in the treatment of acute diarrhea. Aliment Pharmacol Ther. 2012 Aug;36(4):363-9. PMID: 22680836

Fish oil supplementation in early infancy modulates immune responses This double-blind, randomized controlled trial examined the effect of early postnatal fish oil supplementation on infant cellular immune function at six months of age in the context of allergic disease (N = 420). Infants with high atopic risk received fish oil [280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to six months. Blood was collected and analyzed at six months of age in 120 infants and infant allergies were assessed at six and 12 months of age. DHA and EPA levels were significantly higher and erythrocyte arachidonic acid (AA) levels were lower in the fish oil group (all P < 0.05). Infants in the fish oil group had significantly lower IL-13 responses (P = 0.036) to house dust mite and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin. Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL-13 and IL-5 to β-lactoglobulin (P = 0.020 and P = 0.045, respectively). These results suggest that omega-3 fatty acids have immunomodulatory properties (lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses) that are potentially allergyprotective. Clin Exp Allergy. 2012 Aug;42(8):1206-16. PMID: 22805468

Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). This six-week randomized, placebo-controlled trial was conducted to assess the effects of caffeine (100 mg twice daily for three weeks and then 200 mg twice daily for three weeks) upon daytime somnolence, motor severity, and other nonmotor features in 61 PD

patients with daytime somnolence. Caffeine resulted in a non-significant reduction in Epworth Sleepiness Scale score (-1.71 points; 95% CI -3.57 to 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 95% CI 0.16-1.13), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (-1.97; 95% CI -3.87 to -0.05). Caffeine reduced the total Unified Parkinson’s Disease Rating Scale score (-4.69 points; 95% CI -7.7 to -1.6) and the objective motor component (-3.15 points; 95% CI -5.50 to -0.83). Modest improvement in global health measures were found but no changes in quality of life, depression, or sleep quality were noted. The authors concluded that caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Neurology. 2012 Aug 1. PMID: 22855866

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industry news Naturopathic profession recognized under Health Professions Act in Alberta

A new regulation under the Health Professions Act establishes the College of Naturopathic Doctors of Alberta (CNDA) and gives that body the authority to establish requirements for entry into the profession and ongoing professional development. The CNDA serves to define the entry level and continued competence qualifications for Naturopathic Doctors in Alberta; administer standards of practice and professional conduct, and; investigate naturopathic-related complaints on behalf of the public. “Today, Albertans can have confidence when they reach out to a member of the College of Naturopathic Doctors of Alberta, that they have a naturopathic doctor who meets stringent competency and practice requirements,” said Dr. Allissa Gaul, founding president of the CNDA. “We offer Albertans a distinct system of primary health care that is an art, a science, a philosophy and a practice of diagnosis and assessment, treatment and prevention of illness, and we applaud this government for making health and wellness a priority to benefit Albertans.”

Low rates of Influenza immunization in Ontario

A recent study revealed that Influenza vaccine coverage among children aged 6 to 23 months in Ontario is low, despite a universal vaccination program and high primary care visit rates. By using hospital records, all infants born alive in Ontario hospitals from April 2002 through March 2008 were identified. Immunization status was ascertained by linkage to physician billing data and children were categorized as fully, partially, or not immunized depending on the number and timing of vaccines administered. Influenza immunization was low for the first influenza season of the study period (1% fully immunized during the 2002-2003 season), increased for the following three seasons (7% to 9%), but then declined (4% to 6% fully immunized during the 2006-2007 to 2008-2009 seasons). Maternal influenza immunization, having a pediatrician as the primary care practitioner, high visit rates, and better continuity of care were all significantly associated with full immunization. The authors concluded that interventions to improve coverage should target both physicians and families. Pediatrics. 2012 Jun;129(6):e1421-30. PMID: 22585770

Online gout community boasts a large following worldwide

Gout Study has exceeded 50,000 ‘likes’ on Facebook, making it the largest worldwide online gout community. Through this Facebook community, people from around the world are coming together to converse with others about living with this painful condition. Established in March 2011, Gout Study provides news, health, and wellness information, as well as information about clinical research opportunities. Gout Study statistics show how well-received and helpful the various tips and resources are to the community but it is the direct feedback from the community that drives the cause. To learn more about the Gout Study community, “like” the page at www.Facebook.com/GoutStudy.

Over 10,000 donors have provided samples to the Ontario Tumour Bank

The Ontario Tumour Bank (OTB), a province-wide biorepository and data bank led by the Ontario Institute of Cancer Research (OICR), has banked samples from more than 10,000 donors, which is an important milestone for the OTB. Samples collected by the OTB help cancer researchers to analyze cancer at the genetic and molecular level and they are essential to help map the genomic changes present in many forms of cancer. This will help to build the next generation of diagnostic tools and treatments for cancer, including more personalized medicine. For more information, please visit www.ontariotumourbank.ca.

Gamma-Dynacare introduces fecal immunochemical test for colorectal cancer screening

Gamma-Dynacare Medical Laboratories now offers two advanced screening tests for colorectal cancer. GammaDynacare’s fecal immunochemical test (FIT) is a non-invasive test that checks for occult blood in stool using advanced immunochemical technology. Polyps or tumors in the colon have blood vessels on their surface that can release a small amount of blood into the stool. FIT helps identify benign polyps early before they become cancerous. With this technology, FIT has a higher sensitivity than the traditional fecal occult blood test, has no dietary or medicinal restrictions, and requires only one stool sample. GammaDynacare’s other colorectal screening test, Septin9, detects the presence of methylated Septin9 DNA in blood, which has been strongly correlated with an increased risk of colorectal cancer. The test is very convenient since it is performed on a blood sample and has no dietary or medicinal restrictions. For more information on these tests, visit www.gamma-dynacare.com.

New research reveals that bed bugs have the ability to transfer harmful bacteria

For years researchers and scientists have concluded that bed bugs could not transfer dangerous pathogens, but recently published reports have determined that bed bugs have the ability to transfer live staphylococcus aureus (staph). One recent report describes a Tennessee man’s luxurious getaway to a premium rental cabin, which turned into a trip to the emergency room after he received multiple bed bug bites causing a severe bacterial staph infection. Fortunately, the man fully recovered from the infection approximately two weeks later. Magical Pest Control offers a method for eliminating bed bugs through their ThermaPureHeat treatment, which is eco-friendly and pesticide-free. This treatment method penetrates deep into a structure’s cracks and crevices to kill bed bugs and their eggs where they are hiding.

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PRODUCT MONOGRAPH Bio-Fen

Bio-Fen Plus is an oral naturalmonograph health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. Inflammation Relief

Without treatment, AGA is progressive, and causes social distress for in many men and women (Sinclair 1998). Bio-Fen Plus contains extracts BIO-FEN Menaffected and Women of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme Nature’s Anti-Inflammatories Have Issues 5α-reductase. are responsible for relieving symptoms with hereditary AGA. Bio-Fen represents aThese line of inhibitors products by Health Canada hairlinked growth and restoration. Bio-Fen for Men Bio-Fen PlusMany for Women are both oral natural health Chronic inflammation is receiving moreapproved attention than ever before asfor being to much ofassociated the dysfunction andPlus disease facedand by people today. of the popular pharmaceuticals that help Onewith of the primary causes hairoften loss is up a high level ofhealth the male dihydrotestosterone within the hair follicle (Vierhapper, products (NHPs) which support hairofgrowth in men and women with hereditary alopecia (AGA), or to female/male pattern baldness. Bio-Fen contains a combination of deal these rampant health conditions end causing other issuesandrogenic inhormone the long run, causing patients turn (DHT) to the natural health industry for help. Nature offers some2001). powerful herb extracts andwith vitamins & minerals that are often known inhibit enzymeof 5 androgen -reductase (5AR), a keyofto pathway implicated in the toxicity, progression of AGA. For people their follicles havebenefit atogreater number receptors which DHT attaches. 5-α-reductase catalyzes the enzymatic solutions indeed that,AGA, unlike pharmaceuticals, fromthe non-specificity, multiple mechanisms action, considerably lower synergistic action, and sometimes centuries or conversion of testosterone to dihydrotestosterone, binds the receptor five-foldmaking moretherapeutic avidly than the parent compound millennia of medicinal use! Unfortunately, many of these naturalwhich ingredients are to inherently poorly absorbed, concentrations difficult to achieve(Sinclair in tissues 1998). due to bulky AGA Pathophysiology dosing andprimary poor patient oristolerance. Overcoming this issue is nowdihydrotestosterone easier with nanoVAILABLE AOR. One of the causescompliance of hair loss a high level of the male hormone, (DHT)technology within the by hair follicle (Hoffmann 2002). DHT is produced from Saw palmetto repens) testosterone in the(Serenoa testes (males), the adrenal glands, and the follicle. After a period of time, anVitamins over abundance of DHT causes the hair follicle to degrade and shortens the active nanoVAILABLE Inflammation Relief phase of the hair,(lipophillic) eventually leading to thinning hairbeen and eventual Thereinhibitor is a familial In tendency forstudy stepwise the hair follicle and an increase in the calcium ratio a Polish of miniaturization 46 women whoof had symptoms of diffuse alopecia, Standardized Serenoa extract has found tohair be loss. a potent Relief belongs to decreased the(growth new nanoVAILABLE Providing Longvida® curcumin, oleanolic acidorally and administered standardized extracts Boswellia serrata andmg ashwagandha, ofInflammation telogen (resting phase) to anagen phase)DHT. hairs, line which isAOR. promoted by systemic local effects of was androgens. Althou gh everyone only those with pantothenate twiceproduces aofday inDHT, doses of 100 fora four to of 5α-reductase, resulting in tissue Anby open-label, dose responseand Inflammation Relief combines ofinthe most powerful anti-inflammatory extracts with low toxicity risks. designed target chronic inflammation through mechanisms higher of androgen their hair follicles, binding sitesof foraherbal DHT, and greater androgen sensitivity experience hairinjected loss (Prager 2002). 5AR forrepeated the 30multiple days and five months, andIt isvitamin B6towas every day for 20istoresponsible studynumber was conducted onreceptors 42some healthy males to determine the effect combination conversion of testosterone to methods dihydrotestosterone, binds to the sameon androgen but with five-fold greater(Brzezińska-Wcisło affinity. (Hoffmann 2001). 2002, Trueb ofofaction using industry-first to reduce thewhich pillberry burden while increasing effectiveness results. after six months It was2002) determined that vitamin carotenoid astaxanthin and saw palmetto lipid extract DHT receptor, and andagain testosterone levels (Angwafor 2008). The men were divided into two groups:

B6 administered parenterally for a few weeks induces improvement in the hair

The Technology Flax condition in a hair subset women and reduces hair are loss. one groupinhibit received enzyme 800 mg/day of the combination supplement and the other to Flax 5AR, thus balancing formation of the male hormones that arewith responsible lossof (Evans 1995). converted by the This bodytechnology Thelignans equivalent of 8the grams of curcumin (Gota et al, 2010), its therapeutic threshold, is delivered 80 mg offorLongvida® curcumin, usingFlax Solidlignans Lipid ParticleTM technology. group received 2000 mg/daywith of the supplement for 14 days. ANOVA-RM showed enterolactones, which compete estrogen and testosterone for receptor binding, and increase sex hormone binding globulin (SHBG), resulting in loweritlevels of freeII detoxification (ie active) creates nano-miscelle curcumin particles that are small enough to be absorbed through the intestinal wall and into the cells as well as provide a coating that shields from phase significant within-group increases in serum testeosterone significant estrogen and testosterone. Flaxseed has been shown total to reduce serum levelsand of 17-beta-estradiol estrone sulfate (Hutchins 2001), and results in a shift in estrogen metabolism to and permits its entry into the cells. This makes Longvida® the most effective curcumin on the market,and with an increased bioavailability of at least 100 times over that ofPer regular pure curcumin. Medicinal Ingredients Dose Capsule decreases serum DHT baseline in both favor the lessin biologically activefrom estrogens (Brooks 2004).dose groups (P=0.05). There

Boswellia’s therapeutic threshold of 1-3 grams is reached with a self-emulsified Boswellia extract that completely dissolves it in natural oils, reducing the particle size and improving absorption. was no significant difference between dose groups with regard to the increase of Fenugreek (Trigonella foenum graecum)

Ashwagandha oleanolic acidofparticles less thanboth 1 μmdoses in sizewere are the result of(Angwafor nanotechnology, granting them greater access to the bloodstream and tissues. Fenugreek 260 mg testeosteroneand or the decrease DHT; of therefore effective extract 4:1 such as -sitosterol have been shown to block DHT Fenugreek has been used traditionally as an oral and topical treatment for hair loss. Plant sterols seed contained in fenugreek 2008). Studies Clinical receptor sites (Prager 2002, see below).

palmetto berry extract containing 160 mg found significantly One clinical study evaluating the effectiveness of a formula combining Boswellia, ashwagandha,Saw turmeric extract and a zinc complex on osteoarthritis for 3 months

Another study liposterolic extract of1991). Serenoa repens (LSESr) and beta45% free fatty acids Saw Palmetto (men’s product) decreased pain andtested disability scores (Kulkarni et al, sitosterol inextract the treatment of males (23-64 years of age)resulting with mild to moderate AGA. Saw palmetto is a potent inhibitor of 5 -reductase, in decreased tissue DHT (Prager In atopilot of 26tomen with mild to moderate treatment with Curcumin may have more clinical applications than any other herb on the market, ranging from joint pain2002). to ulcers viralstudy inhibition cancer beyond. The mostAGA, impressive studies have Flax lignans, standardized toblinded 20%and Six of 10 (60%) subjectssaw were rated asextract improved at and the beta-sitosterol final visit, thus50mg establishing a combination of lipophilic palmetto 200mg improved symptoms by up to 60%, as scored by assessors (Prager 2002). In a meta 100 mg shown Longvida® curcumin to be safe and therapeutic as an adjunct to cancer treatment (Gota et al, 2010), and recent in vitro studies show inhibition of amyloid plaque aggregation and diglucoside the effectiveness of 5α-reductase inhibitors AGA (Prager 2002). Chronic analysis by the Cochrane group, saw palmetto hasagainst also been found to be effective as a treatment secoisolariciresinol for symptoms of BPH (Wilt 2002). (SDG)

associated neurotoxicity (Huang et al, 2012). A human on the effects of Longvida® on beta-amyloid plaque is awaiting publication. Curcumin is also a renowned inhibitor of inflammation of the hair follicle is considered to bestudy a contributing factor for AGA.curcumin A

D-calcium pantothenate (Vitamin B5) 10.40 mg NF-κB and a powerful antioxidant. Silica (women’s product) study by Chittur et al sought to determine whether blockade of inflammation using Silica isrecently, a and tracetwo mineral that been to found to 5-LOX increase in connective tissue (Barel 2005). In PGE-1 a randomized, double blind, placebo controlled study, Until Boswellia washas though inhibit andhydroxyproline leukotrienes, butconcentration a recent human blood study demonstrated mainly inhibition (Abdel-Tawab et al, 2011). of 50 how LSESr anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg inRegardless women with damaged skin were treated orally 10mg silica as potent, orthosilicic acid 20 weeks. groupmedications reported a significant decrease visualetanalog itthe works, comparative studies have revealed thatwith Boswellia is(Chittur more lessIttoxic, and its daily effectsforlonger lastingThe thantreatment certain NSAID for inflammation (Sontakke al, 2007). expression of molecular markers of inflammation 2009). was (OSA) found scale ratings of hair brittleness (Barel 2005). A second randomized, double blind, placebo controlled trial conducted in 50 women with brittle hair found that 10mg silica as OSA Successful results have been demonstrated in studies using Boswellia serrata for pain andofinflammation in osteoarthritis of the knee ulcerative colitis (Gupta et al, Pyridoxine HCl (Vitamin B6)(Kimmatkar et al, 2003), 2 mg that the combination suppressed lipopolysaccharide-activated gene expression for 9 months significantly improved hair elasticity, breakage, and diameter (thickness) (Wickett 2007).

1997) and asthma (Gupta et al, 1998), although it is also traditionally used forapoptosis. skin health, weakness, immunity and other ailments. chemokines associated with pathways involved in inflammation and Riboflavin (Vitamin B2)

1.58 mg

The study concluded thatcell 5-alpha reductase inhibitors inbeen combination the effects of ashwagandha have shownhormone in vitrowith and in animals by inhibiting NF-κB, it has long been used for this purpose in Ayurvedic medicine and B Although vitamins areanti-inflammatory support healthy growth and division, and mainly facilitate optimal metabolism.

inflammatory could represent a new two-pronged approach isblockade commonlyofused in Ayurvedicprocesses anti-inflammatory formulations (Ichikawa et al, 2006). Ashwagandha is also a popular adaptogen that helps modulate the stress response, Folic acid 0.095 mg providing another Medicinal per capsule in both theactivity, men’swhich and women’s: in the treatment of AGA. avenue foringredients relief of oxidative and inflammatory is often aggravated by stress. Fenugreek (Trigonella foenum graecum) seed extract 4:1 ....................................................260 mg Biotin mcg Oleanolic acid,(dry a triterpenoid naturally present in foods like olive oil, rosemary and thyme, can be found in anti-inflammatory formulations. It was been widely 400 studied for its anti-inflammatory equiv 1040mg) Fenugreek Seeds and chemopreventive activities. Yang and colleagues (2012) recently demonstrated that oleanolic acid inhibits the HMGB1 signaling pathway, which inhibits NF-κB and reduces TNF- α, and it Flax lignans, standardized to 5% 50%to SDG ...............................................................................100 mg Non-Medicinal Ingredients Fenugreek seeds contain 30% protein, steroid saponins, sterols, flavonoids has also been shown to(Vitamin inhibit sPLA2, that promote the formation of eicosanoid pro-inflammatory mediators (Dharmappa et al, 2009). d-calcium pantothenate B5) enzymes ..................................................................................10.4 mg and alkaloids (notably trigonelline and choline). Steroid saponins bind and Niacinamide (Vitamin B3) ...................................................................................................10.3 mg Inert microcrystalline cellulose and vegetable-based magnesium eliminateHCl extra cholesterol and hormones in the body; DHT is made from mg Safety Pyridoxine (Vitamin B6) ...............................................................................................2.0 stearate in a veggie-based capsule testosterone, which in turn have is made fromsafety cholesterol. Therefore, when Curcumin and Longvida® curcumin excellent and low toxicity profiles at theexcess current dose Riboflavin (Vitamin B2)is.......................................................................................................1.6 mg (Cheng et al., 2001; Dadhanyia et al., 2011), with the potential of blood thinning being cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 Folic acidonly ..............................................................................................................................95 mcg and Boswellia. Ashwagandha and oleanolic acid have no reported side effects at these present at very high doses. Minor gastro-intestinal upset have been reported for both curcumin Recommended adult dose: One capsule per day adults....................................................................................................................................250 consumed 12.5g and germinated fenugreek seed powder for Biotin mcg doses. Allwho studies were a minimum of 618.0g weeks of in duration. one month, higher levels of consumption resulted in a significant reduction in total Men’s also has: cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999).

References Saw palmetto berry extract 4:1 .............................................................................................125 mg (dry equiv. 500 mg) Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet. 2011 Jun;50(6):349-69. Flax lignans

Cheng AL, also Hsu CH, Lin JK, Hsu MM, Ho YF et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001 Jul-Aug;21(4B):2895-900. Women’s has: body.(silicon A meta-analysis of 28 studies betweenN,1990 andK,2008 showed Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria Vachhani Soni MG. Chronicthat safetyflaxseed of Longvida.mg Food Chem Toxicol. 2011 May 6. Silicon dioxide) ........................................................................................................40 significantly circulating totalstudy andonLDL-cholesterol concentrations (Pan methane), Iron (ferricSD,citrate) ................................................................................................................20 mg Deodhar Sethireduces R and Srimal RC. Preliminary antirheumatic activity of curcumin (diferuloyl Indian J Med Res 71 (1980), pp. 632-634. Flax reduces the amount of DHT produced by reducing cholesterol levels in the

2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L

Dharmappa Kumar RV, Nataraju Mohamed Shivaprasad HV,per Vishwanath BS.0.00 Anti-inflammatory activity oleanoliceffective acid by inhibition of secretory phospholipase A2. Planta Med. 2009 Feb;75(3):211-5. Recommended use:0.00 one capsuleA,twice capsules bottle). Bio-Fen® Plus capsules areofusually (95% CI: KK, -0.20, mmol/L) and daily 0.08R,(60 mmol/L (95% CI: -0.16, mmol/L), A, Kunnumakkara AB, Aggarwal Curcumin as “Curecumin”: From kitchen to clinic. Biochemical 75, Issue 4, 15 February 2008, Pages 787-809. 4. Satoskar RR, et al. Evaluation of atGoel stopping hair Significant loss within the firstBB. two months. Anyonewith experiencing new growth should see it within Volume four months. respectively. reductions were observed whole flaxseed (-0.21 and Pharmacology Once Bio-Fen is stopped, the hairand growth pattern will and slowly return to its original point, however some people Ther mayToxicol. 1986 Dec;24(12):651-4. anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol -0.16 mmol/L, respectively) lignan (-0.28 -0.16 mmol/L, respectively) beGota ableVS, to Maru continue with lower maintenance dose. MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. supplements (Pan 2009). GB, Soni TG,a Gandhi TR, Kochar N, Agarwal 2010 Feb 24;58(4):2095-9

Bio-Fen has been approved by Health Canada and has received a unique NPN number. In addition to being approved Gupta V,applications, Parihar A, Gupta S, Lüdtkehas R, Safayhi H, Ammonfor HP.additional Effects of Boswellia gum forGupta hair I,growth Bio-Fen been approved health serrata benefits . resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study.

Eur J Med Res. 1998 Nov 17;3(11):511-4. Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, Ammon HP. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res. 1997 Jan;2(1):37-43. Int Soc Sports Nutr 2008;5:12. Contraindications: The ingredient combination in Bio-Fen Plus for Men/Women is generally safe for most adults. Huang HC, Chang P, Dai XL, Jiang Protective effects of curcumin on amyloid-β-induced neuronal oxidative damage. Neurochem Res. 2012 Jul;37(7):1584-97. Bio-Fen should not be used by ZF. patients with diabetes, or known hypersensitivity to any ingredients. Brzezińska-Wcisło L. Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Lek 2001;54:11-8. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB References (NF-kappaB) activation and NF-kappaB-regulated gene expression. Molexpression Cancer Ther. Jun;5(6):1434-45. Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene in 2006 keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based Brooks JD, et al. Am J Clin Nutr. Feb;79(2):318-25. Complement Alternat 2009.L,2004 Kimmatkar N, Thawani V,Med Hingorani Khiyani R. “Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial.” Phytomedicine Evans BA, et al. 1995 Nov;147(2):295-302. 2003 Jan;Yu10(1): 3-7. Pan A, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97. Hoffmann R.D,Clin Exp Dermatol. 2002 Jul;27(5):373-82. Krüger Daneshfar Eckert GP,N, Klein J, Volmer G. DA,ABahr U, Müller WE, Karas M, Schubert-Zsilavecz M, Abdel-Tawab M. Metabolism of boswellicofacids in vitro and in vivo.inhibitors Drug Metab 2008 Jun;36(6):11352001;39(1):58-65. Hutchins AM,et al.R, Nutr Cancer. PragerP,N, Bickett K, French Marcovici randomized, double-blind, placebo-controlled trial to determine the effectiveness botanically derived of Dispos. 5-alpha-reductase in the Prager N, 2008 etof al.androgenetic 2002 treatment alopecia. J Altern Complement Med 2002;8:143-52. 42. Epub Mar 20.Apr;8(2):143-52. Trüeb RM. Exp Aug-Sep;37(8-9):981-90. Kulkarni PatkiGerontol. PS, Jog VP,2002 Gandage SG, Medicine Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991 MaySerenoaRR, repens Alternative Review 1998;3:227-9. Wickett RR, et almonograph. Arch Dermatol Res. 2007 Dec;299(10):499-505. Jun;33(1-2):91-5. Wilt T et al. Database Syst Rev. 2002;(3):CD001423. Sinclair R. Cochrane Male pattern androgenetic alopecia. BMJ 1998;317:865-9. Sharma A, Gupta NK, Dixit VK. Complexation with phosphatidyl choline as a strategy for absorption enhancement of boswellic acid.Drug Deliv. 2010 Nov;17(8):587-95. Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65. Sharma S, Thawani V, Hingorani L, Shrivastava M, Bhate VR, Khiyani R. Pharmacokinetic study of 11-Keto beta-Boswellic acid. Phytomedicine. 2004 Feb;11(2-3):255-60. A, Madar Z. The effect of an Pethanol derived from fenugreek (Trigonellacontrolled foenum-graecum) bile acid absorption and in rats, Br J Nutr 1993;69:277-87. SStark Sontakke, V Thawani, S Pimpalkhute, Kabra, Sextract Babhulkar, L Hingorani. Open, randomized, clinical trialon of Boswellia serrata extract ascholesterol compared tolevels valdecoxib in osteoarthritis of knee. Indian Journal ofVierpper Pharmacology. 2007, 39(1): 27-29. H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4. Suh SJ, et al. Triterpenoid saponin, oleanolic acid 3-O-beta-d-glucopyranosyl(1-->3)-alpha-l-rhamnopyranosyl(1-->2)-alpha-l-arabinopyranoside (OA) from Aralia elata inhibits LPS-induced nitric oxide production by down-regulated NF-kappaB in raw 264.7 cells. Arch Biochem Biophys. 2007 Nov 15 ;467(2):227-33. Yang EJ, Lee W, Ku SK, Song KS, Bae JS. Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs. Food Chem Toxicol. 2012 May;50(5):1288-94.

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industry news London researchers discover novel mechanism involved in key immune response

Researchers at Lawson Health Research Institute and Western University have identified a novel way that the common adenovirus causes disease; this discovery has provided important information on one of the body’s key immune responses and may have implications for infectious diseases and cancer. One key component of antiviral immunity is interferon but adenovirus is completely resistant to interferon and the mechanism relies on changes in epigenetic regulation. The researchers have discovered that interferon-regulated genes require a specific epigenetic modification called monoubiquitination of histone 2B (H2B) to work. Adenovirus essentially blocks the formation of the complex that performs the monubiquitination of H2B, thereby blocking its function. The researchers believe that many of the tricks adenovirus uses may be similar to those used by other viruses and cancer cells.

Canadian researchers discover promising new treatment for Ebola infection

Researchers at the Public Health Agency of Canada’s National Microbiology Laboratory (NML) have developed a new and easy-to-manufacture treatment for Ebola infection. Up to 90% of infections result in death within days of exposure. Given that no approved Ebola vaccine prevents infection, there is an urgent need for a treatment to improve survival rates after exposure. This new treatment can be effective when administered up to 48 hours after infection. “Our researchers have seen first hand the terrible effects of the Ebola virus on populations in Africa,” said Dr. Frank Plummer, Chief Science Officer at the Public Health Agency of Canada. “This discovery should pave the way for the development of a new drug that has the potential to save many lives.”

Nordic Naturals® introduces vegetarian alternative

Nordic Naturals®, the leading manufacturer of omega-3 supplements, has introduced Algae Omega™, a vegetarian alternative to marine omega-3s. Made from sustainably sourced microalgae and available in both soft gels and liquid, the product offers an algaebased source of beneficial marine omega-3 essential fatty acids without the use of fish. “In order to support our mission of correcting the global omega-3 deficiency, we are committed to bringing innovative new products to market in order to meet the individual needs of our customers,” said Joar Opheim, founder and CEO of Nordic Naturals. “We formulated Algae Omega with vegetarians in mind, and for anyone wanting a readily available, high-quality source of EPA and DHA from a non-fish source.” While algae oil is typically rich in DHA, Algae Omega™ is uniquely formulated to contain significant amounts of EPA as well. The product delivers 500 mg of combined EPA and DHA, offering complete nutritional support for normal vision, heart health, positive mood, immunity, and the body’s natural anti-inflammatory response.

Report card on wait times in Canada shows longer waits for patients

The Wait Time Alliance (WTA) warns that the absence of a concerted national effort to reduce wait times is undermining progress on addressing the time lags endured by Canadians needing medical care. The 2012 WTA report card, entitled “Shedding Light on Canadians’ Total Wait for Care,” gives Canadians a picture of how long they have to wait to access a broad range of medical procedures and services. In a reversal from past years, the 2012 Report Card shows a decline in performance for patients receiving care in the five areas identified as priorities by federal, provincial, and territorial governments under the 2004 Health Accord. Most efforts to date in Canada have been directed at improving the wait between the specialist consultation and the start of treatment but many Canadians are also waiting to see their family physician, obtain medical tests, and be seen by a specialist.

The OAND announces the departure of Alison Dantas

The Ontario Association of Naturopathic Doctors has announced the departure of Chief Executive Officer (CEO), Alison Dantes, which became effective on July 19, 2012. Alison has accepted an offer for a CEO position with another federal professional association in the healthcare sector. The OAND notes that Alison made a tremendous contribution to this association and the profession over the past six years and states that she will surely be missed. Alison successfully led the OAND through many impressive accomplishments and in years to come, these new directions led by Alison will be viewed as a turning point for naturopathic doctors in Ontario. The Board and staff of the OAND wishes Alison all the very best. With a strong OAND staff team and an interim operational leadership structure in place reporting directly to the Board, the Board is now actively engaged with an executive recruitment firm and ensures OAND members that the right competency and capabilities are brought back into the CEO position for the next phase of growth and advancement.

Dietary supplement reduces frequent urination

A recent clinical study on SagaPro, an Icelandic natural product has shown it to be effective against nocturia in those with low or diminished bladder capacity. SagaPro, which is made from Angelica archangelica, has been produced by SagaMedica in Iceland since 2005 and is very popular among nocturia sufferers. In the placebo-controlled study (N = 69), which will be published in the Scandinavian Journal of Urology and Nephrology, participants with lower urinary tract symptoms were required to keep a detailed record of their nocturnal restroom trips as well as the volume of urine before and after a period of eight weeks while they took either SagaPro or a placebo. SagaPro was found to have a pronounced effect on bladder volume and urinary frequency, two factors that affect the duration and quality of sleep. www.ihpmagazine.com l October 2012 21

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industry news Pediatric Inflammatory Bowel Disease Research Network has been launched

The Foundation for Children with Intestinal and Liver Disorders (CH.I.L.D) have partnered with the Canadian Institutes of Health Research (CIHR) to fund the creation of the Canadian Children Inflammatory Bowel Disease Network: A Joint Partnership of CIHR and the CH.I.L.D. Foundation. This national research network and data platform aims to pursue a cure for Inflammatory Bowel Disease (IBD) in children and to improve the quality of care for patients and their families who suffer from these debilitating diseases. This partnership will produce a framework to bring researchers and stakeholders together to work collectively with their focus on a cure for pediatric IBD, opening up opportunities to exchange information with researchers, patients, and families. CIHR and CH.I.L.D. have launched a competition open to the best Canadian researchers in the field to create a network of at least five centres of pediatric IBD research expertise across the country; the national network will help establish a framework to share the latest advances and best ideas in treating children with IBD, and to apply them in new treatment regimens built on the principles of standardized high quality patient focused care.

First ever trial comparing robotic surgery to radiation therapy

Lawson Health Research Institute has announced the launch of the ORATOR trial. This landmark study is the first trial in the world to compare robotic surgery to radiation for the treatment of oropharyngeal cancer. The study will examine the impact of both treatments on patients’ speech and swallowing function, and quality of life as a first step toward identifying the best treatment for patients.

Lawsuit filed over plant sterol claims in Smart Balance spreadable butter

A class action lawsuit has been filed against Smart Balance alleging that it does not include enough plant sterols in its spreadable butters to warrant the cholesterollowering health claim on the package label. The plaintiff acknowledges that while plant sterols can help lower cholesterol (at a minimum daily dose of 0.8 grams daily and a preferable daily dose of 2 grams), Smart Balance Spreadable Butter does not have sufficient levels of sterols to reduce cholesterol, containing only 100mg of plant sterols per 14 gram serving. The plaintiff states that Smart Balance is giving a false and misleading message since consumers eating about 15 tablespoons of the spread would still fall short of the 2 gram per day recommendation.

New range of dietary supplements formulated that targets cancer patients undergoing treatment

OncoQOL is a new range of products offered by Thorne Research and The Helsinn Group that was formulated for cancer patients who often suffer from chemotherapyinduced fatigue, gastrointestinal problems, and nutrient deficiencies. The range of products includes: (1) DaxibeQOL, which is a blend of branched-chain and other essential amino acids that may promote anabolism, weight gain, lean muscle mass, and muscle strength; (2) NutraQOL, which is a wheat germ extract that may reduce fatigue and helps improve social, physical, and emotional wellbeing; and (3) VitaQOL, which is a mix of essential vitamins and minerals without excessive amounts of antioxidants that can interfere with cancer treatment. The range of products is available exclusively through oncologists and other medical professionals in the US and Canada. “For many cancer patients the side effects of treatment have a significant impact on their health and quality of life, often making it difficult for them to continue with their therapy,” said OncoQOL science advisory board chair James B. LaValle, RPh. “Our products are designed to meet the unique needs of these patients.

Gamma-Dynacare Medical Laboratories acquires Maxxam Analytics’ Drug and Alcohol Testing

Gamma-Dynacare Medical Laboratories has acquired the drug and alcohol testing business of Maxxam Analytics, a leading provider of analytical services and solutions to the energy, environmental, food, and DNA industries. “This acquisition expands our toxicology business and establishes GammaDynacare as the industry leader in the provision of drug and alcohol testing in Canada,” said Naseem Somani, President and Chief Executive Officer, GammaDynacare Medical Laboratories. “We are expecting this important market to grow significantly over the next few years as more organizations adopt random testing programs to improve workplace and public safety as well as productivity.”

Homewood Human Solutions launches a health and wellness social media program

Homewood Human Solutions™ is an industry leader and pioneer in mental health and addictions, organizational health, and Employee and Family Assistance Programs. It is pioneering the use of social media to provide Canadians with expert and meaningful health and wellness information, including a blogging website (http:// www.healthyworkplaces.info) that is packed with posts by medical and organizational health experts. Research finds that 68% of Canadian adults use a general search engine such as Google to research health and wellness topics and 34% of people searching for healthrelated information use social media. This figure is much higher with the 18 to 24 year old demographic. The social networking project will offer the latest breaking health news, pertinent opinions, information on national conferences, articles from around the world, and research materials. Homewood Human Solutions’ online community is located on Facebook, Twitter, Linkedin, and http://www.healthyworkplaces.info. ■

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TM

For Details, write #114 on Free Info Page, page 96.

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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OF OREGANO

Oil of Oregano is a hydrophobic extract of Origanum vulgare leaf. Major active constituents include the monoterpene phenolic compounds carvacrol and thymol. Carvacrol and thymol are potent antimicrobials with synergistic bactericidal, fungicidal, and antihelminthic activity.

Human studies

Oil of Mediterranean Oregano had antihelminthic effects when given at 600 mg emulsified oil per day in 14 adults who had tested positive for enteric parasites Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana. After 6 weeks of treatment, there was complete resolution of parasitic infection in 8 cases, while Blastocystis hominis scores decreased in three more cases; gastrointestinal symptoms improved in 7 of the 11 subjects who had presented with Blastocystis hominis infection. (Force 2000)

Animal and In vitro studies

Carvacrol for oral candidiasis in immunocompromised rats was found to be as effective as treatment with Nystatin, reducing the number of colony forming units (CFU’s) and completely clearing hyphae from oral surfaces when given for 8 days (Chami 2004). In vitro, carvacrol was determined to exert an inhibitory effect against 6 different strains of Candida species primarily due to extensive lesion of the plasma membrane (Salgueiro 2003). Carvacrol has potent antimicrobial activity against several microbial species, including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Psuedomonas aeruginosa, Candida albicans, and Aspergillus niger; out of these, Candida albicans has been found most susceptible (Santoyo 2006). Carvacrol and thymol are thought to exert an additive effect by disrupting bacterial membrane integrity (Lambert 2001). Oregano has been shown to inhibit Methicillin resistant strains of Staph.

Figure 1: Structure of Carvacrol (left) and Thymol (right)

aureus and epidermis, and attenuates biofilm formation in vitro (Nostra 2004; 2007).

Toxicology

Essential oil extracts are categorically known to be toxic in high doses, and are therefore typically given in drop doses; essential oils should not be used internally by pregnant or breastfeeding women. Animal studies to date, however, indicate relative safety of Oregano oil. Carvacrol was shown to be hepatoprotective against ischemia and reperfusion injury in rats; both carvacrol and silymarin had similar beneficial effects on AST and ALT levels (Canbek 2007). Carvacrol also increased liver regeneration rate in rats after partial hepatectomy (Uyanoglu 2008). Mutagenicity studies of carvacrol show only weak activity; carvacrol is excreted in urine after 24 hours in large quantities, unchanged or as glucoronide and sulphate conjugates (De Vincenzi 2004).

References

Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser K. Effects of carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine. 2008 Jan. De Vincenzia M et al. Constituents of aromatic plants: carvacrol. Fitoterapia 2004; 75(7-8): 801-804. Force M et al. Inhibition of enteric parasites by emulsified oil of oregano in vivo. Phytother Res. 2000 May;14(3):213-4. Lambert RJ, Skandamis PN, Coote PJ, Nychas GJ. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J Appl Microbiol. 2001 Sep;91(3):453-62. Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA, Pizzimenti FC, Cioni PL, Procopio F, Blanco AR. Effects of oregano, carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Med Microbiol. 2007;56(Pt 4):519-23. Nostro A et al. Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS Microbiol Lett. 2004;230(2):191-5. Salgueiro LR et al. Chemical composition and antifungal activity of the essential oil of Origanum virens on Candida species. Planta Med. 2003 Sep;69(9):871-4. Santoyo S, Cavero S, Jaime L, Ibañez E, Señoráns FJ, Reglero G. Supercritical carbon dioxide extraction of compounds with antimicrobial activity from Origanum vulgare L.: determination of optimal extraction parameters. J Food Prot. 2006;69(2):369-75. Uyanoglu M, Canbed M, Aral E, Husnu Can Baser K. Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. Phytomedicine 2008; 15(3): 226-9. ihpSept10_NAHS_Ad.indd 2 058.IHP NAHS mono.indd 1 IHPAPR2012_10055_North_American_Herb_and_Spice_FP.indd 2

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calendar October

October 17 Holistic Approach to Dental and Oral Health Organized by: Ontario Association of Naturopathic Doctors Webinar For more information, visit www.oand.org October 17 Canadian Nutrition Labelling Organized by: Guelph Food and Technology Centre Guelph, Ontario For more information, visit www.gftc.ca/courses-and-training October 17 Constitutional/Traditional Immune Support Organized by: Emerson Ecologics Webinar For more information, visit www.emersonecologics.com October 18-20 Aging in a Changing World: Canadian Association on Gerontology’s 41st Annual Scientific and Educational Meeting Organized by: Canadian Association on Gerontology Vancouver, British Columbia For more information, visit www.cagacg.ca October 18-19 Health Information Privacy and Security (HIPS) Summit Organized by: University of Alberta Banff, Alberta For more information, visit http://hpi.uaextension.ca October 18-23 48-Hour Nutrition Certification Series Organized by: Metagenics Inc. Montreal, Quebec For more information,call 281-286-6040 October 20 Relieving the Burden of Somatovisceral Disorders Organized by: Canadian Memorial Chiropractic College

Toronto, Ontario For more information, visit www.cmcc.ca October 20-21 Humanity’s Greatest Threat: Advanced Modalities and Supportive Care for Your Cancer Patient Workshop Organized by: Seroyal Seattle, Washington For more information, visit www.seroyalseminars.com October 20-21 Radiology 2012: Calgary Organized by: Canadian Memorial Chiropractic College Calgary, Alberta For more information, visit www.cmcc.ca October 24 Medical Food 101 – Understanding the Applications of Our Medical Foods Organized by: Metagenics Inc. Webinar For more information, visit www.metagenics.com October 24 Pain Management: Radical New Science Revolutionizes Trans-dermal Healing Organized by: Seroyal Webinar For more information, visit www.seroyalseminars.com October 24-26 4th Conference on Recent Advances in the Prevention and Management of Childhood & Adolescent Obesity Organized by: University of British Columbia Halifax, NS For more information, visit www.interprofessional.ubc.ca/obesity/ October 26 A Day of Derm for GPs Organized by: Tamarind Healthcare Ottawa, Ontario For more information, visit http://dermdayforgps.ca

October 27 Individualized Nutrition: Addressing Biochemical Individuality for Optimal Health and Well-being Organized by: Seroyal Toronto, Ontario For more information, visit www.seroyalseminars.com October 27-28 Diversified Technique Workshop Organized by: Canadian Memorial Chiropractic College Toronto, Ontario For more information, visit http://www.cmcc.ca October 28 Opioid Dependence Treatment Core course - Workshop Organized by: Centre for Addiction and Mental Health Toronto, Ontario For more information, visit http://www.camh.ca October 29 Psychosocial Care of the Dying and Bereaved Organized by: Victoria Hospice Victoria, British Columbia For more information, visit www.victoriahospice.org

November

November 2 Cardio-Metabolic Summit Ottawa Organized by: Canadian Heart Research Centre Ottawa, Ontario For more information, visit www.chrc.net November 2 Heart and Stroke Level A (CPR refresher) Organized by: BRB CE Group Gormley, Ontario For more information, visit http://brbcegroup.com

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product profiles

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r s y s s e g h n h al ine ine thy alt sur nce ete iatr tric tric itio alt tic llin a c c se ceu edi edi eop He res Ca iab ych edia eria utr e He n r N n D Ps P P u a G l ra n M l M om o s t d t u u a C Nu H or m sc loo sia nic / et Sp Im Va B Di nal . A ota io B ad r rt it T Nu

Progressive Vitamin C Complex Progressive Vitamin C Complex provides the optimum potency, balance and absorption that you need to get the benefits and antioxidant protection you want. Isolated sources offer greater potency while whole food ingredients create the natural balance and bioavailability you need. It also contains papaya and black pepper extract to improve the passage of nutrients into your blood stream.

Genestra Brands™ Mag Cal Vanilla Liquid A high-dose 2:1 ratio of magnesium : calcium. The formula uses the bio-available citrate forms of magnesium and calcium and also includes vitamin D3. Ideal for vegetarians. Great tasting vanilla flavour. Helping to support individualized treatments begins with a large array of Genestra Brands™ calcium and magnesium supplements. With a variety of formats, dosagesand sources, Genestra Brands™ has been providing healthcare practitioners with proven safe, effective and reliable products for over 27 years. Don’t forget to try out our cal:mag liquid formulations in delicious natural spearmint, fruit punch and raspberry flavours.

Inflammation Relief Cut down on large dosing regimens and improve patient compliance with AOR’s nanoVAILABLE technology. AOR’s nanoVAILABLE Inflammation Relief pairs cutting-edge technology with powerful traditional anti-inflammatory extracts including ashwagandha, Boswellia, Longvida® curcumin and oleanolic acid, relieving chronic inflammation more easily, naturally and effectively in the smallest dose possible.

EPO SAP Evening primrose oil (EPO) contains essential fatty acids that have several beneficial effects in the body. EPO is a source of gamma-linolenic acid (GLA) which, when used topically, has been demonstrated to aid in the management of atopic dermatitis. EPO also contains precursors of prostaglandin E1 which, when deficient, can contribute to many female hormone balancing concerns, including PMS symptoms such as depression, irritability, breast pain and fluid retention. Deficiency of prostaglandin E1 can also contribute to menopausal symptoms including hot flashes. EPO also inhibits leukotriene synthesis, which is an inflammatory mediator and can therefore be used to reduce systemic inflammation in the body. 26 www.ihpmagazine.com l October 2012

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testosterone to DHT (which is the primary molecule that causes hair loss). The SDG from flax lignans in both formulas also decreases excess cholesterol - the building block of testosterone. Based on new research on the rate of metabolism of SDG in flax lignans (8-12 hours on average), the dosage in both products has been revised from once a day to twice a day for optimum results.

Twice the Strength! Double the Power! Bio-Fen® Plus for Men: The mechanism that causes AGA in men follows the same pathway that results in benign prostatic hyperplasia (BPH). For example, the prescription drug finasteride also works by blocking the enzyme 5αreductase and is used as a treatment for both BPH and AGA. For AGA it is marketed under the brand name of Propecia, but the exact same molecule for BPH is sold under the name of Proscar. Hair Grow Technology’s Bio-Fen® product line is continually moving forward! We are introducing our two latest versions; Bio-Fen® Plus for Men and Bio-Fen® Plus for Women. These products have been assigned Natural Product Numbers (NPN’s) by the Natural Health Products Directorate (NHPD) of Health Canada. We recognize that both men and women experience androgenic alopecia (AGA, or male / female pattern baldness) and have made some improvements to the original formulation based on the latest science to address their specific needs. You will notice that we now have additional complementary (Health Canada Approved) health claims on each product.

What causes hereditary hair loss? Each hair grows from a pocket in the skin called the hair follicle. During its growing phase the follicle has a bulb-shaped bottom, the center of which is called the dermal papilla. The paplla is fed by very small blood vessels, which bring it food, oxygen and remove wastes. The papilla is highly sensitive to hormones and chemicals secreted by the body (or ingested as a medicine) which impacts hair growth It is believed that some individuals have a genetic predisposition to a receding hairline (most common in men) or hair (follicle) thinning over larger areas of the scalp (more common in women). These conditions result from hormonal changes caused by an enzyme in the dermal papilla called 5-alpha-reductase. This enzyme breaks down the hormone testosterone into dihyrotestosterone (DHT). Over a period of time, an over abundance of DHT causes the hair follicle to degrade and shortens the active phase of the hair, eventually leading to thinner hair and eventual hair loss.

How does Bio-Fen® PLUS work? We are bringing you two new products with double the number of capsules and triple the number of health claims for men and four times the number of health claims for women, As in the previous formulation, the fenugreek seed extract in both new formulas reduces excess blood lipid levels (hyperlipidemia). Fenugreek contains β-sitosterol, an active plant sterol, which has been shown to inhibit 5-alphareductase activity – the enzyme responsible for converting excess

As before, the saw palmetto extract inhibits the enzyme 5-alpha reductase, and this action slows down the conversion of testosterone to dihydrotestosterone (or DHT) – the overabundance of which causes the miniaturization of hair follicles. This activity of the saw palmetto also helps to relieve the urinary symptoms of mild to moderate BPH for men. The saw palmetto that originally was an extract standardized to 45% free fatty acids, esters, and sterols while the new formula is a 4:1 extract to support the BPH claim. The product still contains these molecules for hair loss, but they are now at proprietary amounts based on our research so that the competition cannot duplicate our formula.

Bio-Fen® Plus for Men will also help to: • Relieve the urologic symptoms associated with mild to moderate benign prostatic hyperplasia - BPH (e.g. weak urine flow, incomplete voiding, frequent daytime and night time urination). • Reduce elevated blood lipid levels / hyperlipidemia.

Bio-Fen® Plus for Women: The women’s formula is almost the same as the men’s formula. The mechanisms and results for the women formula is the same. The only difference is it contains silicon and iron instead of saw palmetto. Silicon has been shown to contribute to hair shaft strength and thus healthy hair growth. It also contains iron which helps prevent iron deficiency. A number of studies have related sub-clinical iron deficiency in women to diffuse hair loss/alopecia. The increased amount of SDG and other revisions to the regulations allow us to make some additional health claims for Bio-Fen® Plus for Women.

Available at Health Food Stores and Independent Pharmacies

Hair Grow Technology Inc.

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Bio-Fen® Plus for Women will also help to: • Reduce elevated blood lipid levels/hyperlipidemia • Prevent iron deficiency. • Metabolize carbohydrates, fats and proteins.

How long must I use Bio-Fen® Plus? Bio-Fen® Plus for Men capsules are usually effective at stopping hair loss within the first two months. However, since healthy hair grows only about 1 cm each month, it may take up to three months before you notice that hair growth is increased or the rate of hair loss is decreased. Anyone experiencing new growth should see it within four months. In some people the original pigmentation may come back. Once you stop completely your hair growth pattern will slowly go back to the point where you started. However, some people may be able to go with a lower maintenance dose.

Why has the recommended dose doubled? Based on new research on the rate of metabolism of SDG in flax lignans (8-12 hours on average), the dosage in both products has been increased to twice a day for optimum results. The flax lignan extract in the original formulation was 100 mg standardized to 20% SDG x 1 capsule per day, which equaled to 20 mg/day of SDG. The new formulations have 200 mg per capsule of flax lignan extract standardized to 50% SDG x 2 caps/day equals 200 mg/day of SDG. As such, one is getting 10 times the amount of SDG per day!.

How safe is Bio-Fen® Plus? The ingredient combination in Bio-Fen® Plus is generally safe for most adults. However, the following cautions are advised: For Men: Consult a health care practitioner prior to use to exclude a diagnosis of prostate cancer, or if you have diabetes. For BPH or elevated blood lipid levels, consult a health care practitioner if symptoms persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). For Women: Consult a health care practitioner prior to use if you are pregnant or if you have diabetes. Consult a health care practitioner if elevated blood lipid levels persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). Because of the iron content, some people may experience constipation, diarrhea and/or vomiting. Keep out of the reach of children. There is enough iron in this package to seriously harm a child.

1-866-424-7745 • www.biofen.com

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PRODUCT MONOGRAPH Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. Without treatment, AGA is progressive, and causes social distress for in many men and women (Sinclair 1998). Bio-Fen Plus contains extracts BIO-FEN Menaffected and Women of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme 5α-reductase. are responsible for relieving symptoms associated withPlus hereditary AGA. Bio-Fen represents aThese line of inhibitors products approved by Health Canada for hair growth and restoration. Bio-Fen for Men and Bio-Fen Plus for Women are both oral natural health One of the primary causes hair loss is and a high level of hereditary the maleandrogenic hormonealopecia dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001). products (NHPs) which support hairofgrowth in men women with (AGA), or female/male pattern baldness. Bio-Fen contains a combination of herb extracts andwith vitamins & minerals that are known inhibit the enzymeof 5 androgen -reductase (5AR), a keyto pathway in the progression of AGA. catalyzes the enzymatic For people AGA, their follicles have atogreater number receptors whichimplicated DHT attaches. 5-α-reductase conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998). AGA Pathophysiology One of the primary causes of hair loss is a high level of the male hormone, dihydrotestosterone (DHT) within the hair follicle (Hoffmann 2002). DHT is produced from Saw palmetto repens) testosterone in the(Serenoa testes (males), the adrenal glands, and the follicle. After a period of time, anVitamins over abundance of DHT causes the hair follicle to degrade and shortens the active phase of the hair,(lipophillic) eventually leading to thinning hairbeen and eventual Thereinhibitor is a familial In tendency forstudy stepwise the hair follicle and an increase in the calcium ratio a Polish of miniaturization 46 women whoof had symptoms of diffuse alopecia, Standardized Serenoa extract has found tohair be loss. a potent of of telogen (resting phase) to anagen (growthtissue phase)DHT. hairs, which is promoteddose by systemic effects of was androgens. Althou gh everyone thosemg with pantothenate orally administered twiceproduces a day inDHT, dosesonly of 100 fora four to 5α-reductase, resulting in decreased An open-label, responseand local higher of androgen in their binding sitesof fora DHT, and greater five androgen sensitivity experience hairinjected loss (Prager 5AR forrepeated the 30 days and months, and vitamin B6 was every2002). day for 20istoresponsible studynumber was conducted onreceptors 42 healthy maleshair to follicles, determine the effect combination conversion of testosterone to dihydrotestosterone, binds to the sameon androgen but with five-fold greater(Brzezińska-Wcisło affinity. (Hoffmann 2001). 2002, Trueb again after six months It was2002) determined that vitamin of carotenoid astaxanthin and saw palmettowhich berry lipid extract DHT receptor, and

testosterone levels (Angwafor 2008). The men were divided into two groups:

B6 administered parenterally for a few weeks induces improvement in the hair

Flax condition in subset women and Flax reduces hair are loss. onelignans groupinhibit received 800 mg/day of the combination supplement the other Flax the enzyme 5AR, thus balancing formation of the maleand hormones that are responsible fora hair lossof(Evans 1995). lignans converted by the body to group received 2000 mg/daywith of the supplement for 14 days. ANOVA-RM enterolactones, which compete estrogen and testosterone for receptor binding,showed and increase sex hormone binding globulin (SHBG), resulting in lower levels of free (ie active) significant within-group increases in serum total testeosterone and significant estrogen and testosterone. Flaxseed has been shown to reduce serum levels of 17-beta-estradiol and estrone sulfate (Hutchins 2001), and results in a shift in estrogen metabolism to Medicinal Ingredients Dose Per Capsule decreases serum DHT baseline in both favor the lessin biologically activefrom estrogens (Brooks 2004).dose groups (P=0.05). There

was no significant difference between dose groups with regard to the increase of

Fenugreek (Trigonella foenum graecum)

Fenugreek 260 mg testeosterone or the decrease of DHT; therefore both doses were effective (Angwafor seed extract 4:1 Fenugreek 2008). has been used traditionally as an oral and topical treatment for hair loss. Plant sterols contained in fenugreek such as -sitosterol have been shown to block DHT receptor sites (Prager 2002, see below).

Saw palmetto berry extract containing

160 mg

Another study tested liposterolic extract of Serenoa repens (LSESr) and beta45% free fatty acids Saw Palmetto (men’s product) sitosterol inextract the treatment of males (23-64 of age)resulting with mild to moderate AGA. Saw palmetto is a potent inhibitor of 5 years -reductase, in decreased tissue DHT (Prager 2002). In a pilot study of 26 men with mild to moderate AGA, treatment with Flax lignans, standardized toblinded 20% assessors (Prager 2002). In a meta Six of 10 (60%) subjectssaw were rated asextract improved at and the beta-sitosterol final visit, thus50mg establishing a combination of lipophilic palmetto 200mg improved symptoms by up to 60%, as scored by 100 mg diglucoside the effectiveness of 5α-reductase inhibitors AGA (Prager 2002). Chronic analysis by the Cochrane group, saw palmetto hasagainst also been found to be effective as a treatment secoisolariciresinol for symptoms of BPH (Wilt 2002). (SDG) inflammation of the hair follicle is considered to be a contributing factor for AGA. A

D-calcium pantothenate (Vitamin B5) 10.40 mg Silica (women’s product) study by Chittur et al sought to determine whether blockade of inflammation using Silica is a and tracetwo mineral that has been found to increase hydroxyproline in connective tissue (Barel 2005). In a randomized, double blind, placebo controlled study, 50 LSESr anti-inflammatory agents (carnitine and thiocticconcentration acid) could alter Niacinamide (Vitamin B3) 10.25 mg women with damaged skin weremarkers treated orally with 10mg silica as orthosilicic the expression of molecular of inflammation (Chittur 2009). It acid was (OSA) found daily for 20 weeks. The treatment group reported a significant decrease in visual analog scale ratings of hair brittleness (Barel 2005). A second randomized, double blind, placebo controlled trial conducted in 50 women with brittle hair found that 10mg silica as OSA Pyridoxine HCl (Vitamin B6) 2 mg that the combination suppressed lipopolysaccharide-activated gene expression of for 9 months significantly improved hair elasticity, breakage, and diameter (thickness) (Wickett 2007). chemokines associated with pathways involved in inflammation and apoptosis.

Riboflavin (Vitamin B2)

1.58 mg

Folic acid

0.095 mg

study thatcell 5-alpha inhibitors in combination withmetabolism. B The vitamins are concluded support healthy growthreductase and division, and facilitate optimal hormone

blockade of inflammatory processes could represent a new two-pronged approach Medicinal ingredients per capsule in both the men’s and women’s: in the treatment of AGA.

Fenugreek (Trigonella foenum graecum) seed extract 4:1 ....................................................260 mg Biotin 400 mcg equiv 1040mg) Fenugreek (dry Seeds Flax lignans, standardized to 5% 50%to SDG ...............................................................................100 mg Non-Medicinal Ingredients Fenugreek seeds contain 30% protein, steroid saponins, sterols, flavonoids d-calcium pantothenate (Vitamin B5) ..................................................................................10.4 mg and alkaloids (notably trigonelline and choline). Steroid saponins bind and Niacinamide (Vitamin B3) ...................................................................................................10.3 mg Inert microcrystalline cellulose and vegetable-based magnesium eliminateHCl extra cholesterol and hormones in the body; DHT is made from mg Pyridoxine (Vitamin B6) ...............................................................................................2.0 stearate in a veggie-based capsule testosterone, which is in turn is made from cholesterol. Therefore, when excess Riboflavin (Vitamin B2) .......................................................................................................1.6 mg cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 mcg Folic acid ..............................................................................................................................95 Recommended adult dose: One capsule per day adults....................................................................................................................................250 who consumed 12.5g and 18.0g of germinated fenugreek seed powder for Biotin mcg

one month, higher levels of consumption resulted in a significant reduction in total

Men’s also has: cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999). Saw palmetto berry extract 4:1 .............................................................................................125 mg (dry equiv. 500 mg) Flax lignans

Flax reduces the amount of DHT produced by reducing cholesterol levels in the

Women’s also has: body.(silicon A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed mg Silicon dioxide) ........................................................................................................40 significantly reduces circulating total and LDL-cholesterol concentrations (Pan mg Iron (ferric citrate) ................................................................................................................20

2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L

Recommended use:0.00 one mmol/L) capsule twice capsules perCI: bottle). Bio-Fen® Plus capsules are usually effective (95% CI: -0.20, and daily 0.08 (60 mmol/L (95% -0.16, 0.00 mmol/L), at respectively. stopping hair Significant loss within the first two were months. Anyonewith experiencing new growth reductions observed whole flaxseed (-0.21should and see it within four months. Once Bio-Fen is stopped, the hairand growth pattern will and slowly return to its original point, however some people may -0.16 mmol/L, respectively) lignan (-0.28 -0.16 mmol/L, respectively) besupplements able to continue with a lower maintenance dose. (Pan 2009). Bio-Fen has been approved by Health Canada and has received a unique NPN number. In addition to being approved for hair growth applications, Bio-Fen has been approved for additional health benefits. Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J Int Soc Sports Nutr 2008;5:12.

Contraindications: The ingredient combination in Bio-Fen Plus for Men/Women is generally safe for most adults. Bio-Fen should not be used by patients withB6 diabetes, or known hypersensitivity to any ingredients. Brzezińska-Wcisło L. Evaluation of vitamin and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Lek 2001;54:11-8.

References Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based Brooks JD, et al. Am J Clin Complement Alternat Med Nutr. 2009. 2004 Feb;79(2):318-25. Evans BA, et al. 1995 Nov;147(2):295-302. Pan A, YuR.D,Clin Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97. Hoffmann Exp Dermatol. 2002 Jul;27(5):373-82. 2001;39(1):58-65. Hutchins AM,et al.K, Nutr Cancer. Prager N, Bickett French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the Prager N, etof al.androgenetic 2002 Apr;8(2):143-52. treatment alopecia. J Altern Complement Med 2002;8:143-52. Trüeb RM. Exp Gerontol. 2002 Aug-Sep;37(8-9):981-90. Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9. Wickett RR, et al Arch Dermatol Res. 2007 Dec;299(10):499-505. Wilt T et al. Database Syst Rev. 2002;(3):CD001423. Sinclair R. Cochrane Male pattern androgenetic alopecia. BMJ 1998;317:865-9. Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87. Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

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product profiles

Legend

r s y s s e g h n h al ine ine thy alt sur nce ete iatr tric tric itio alt tic llin a c c se ceu edi edi eop He res Ca iab ych edia eria utr e He n r N n D Ps P P u a G l ra n M l M om o s t d t u u a C Nu H or m sc loo sia nic / et Sp Im Va B Di nal . A ota io B ad r rt it T Nu

Boswellia Boswellia serrata, or Indian frankincense, is traditionally used to reduce inflammation and joint pain and is clinically effective in reducing knee pain caused by osteoarthritis, among other inflammatory conditions. AOR’s nanoVAILABLE Boswellia uses a self-emulsification technology that in essence pre-digests the herb, enhancing its absorption and effectiveness in just 3 capsules per day.

Genestra Brands™ Active Chewable B12 Essential vitamin B12 formula (Methylcobalamin ) in a natural cherryflavoured chewable format for convenient patient compliance. This product is part of the new Genestra Brands™ Active B Co-enzymatic vitamin family. The ACTIVE vitamin B’s utilize premium source ingredients such as methylcobalamin, Metafolin®, riboflavin-5-phosphate and pyridoxal-5-phosphate. These are in the body’s most preferred active forms, helping to provide support to energy production and metabolic processes.

Ester-C ® Supreme Ester-C vitamin C contains active vitamin C metabolites including L-threonate, which enhance cellular absorption and retention, and has been clinically proven to remain in the white blood cells of the immune system for up to 24 hours. SISU Ester-C Supreme is a citrus-free blend that includes quercetin, berry bioflavonoids and larch arabinogalactan, to provide antihistamine, antioxidant and antiinflammatory properties and protect against allergies, colds, and flu

o3mega triple strength + D3 Just one capsule provides the recommended daily dose of 900mg of EPA/DHA for cardiovascular support, and 1,000 IU of vitamin D3. Our Omega-3 is independently tested to be pure, fresh and free of all toxins and PCBs. Pure, Wild, Fresh, Toxin & Phthalate-Free; id System™ enteric coated; 5 Star IFOS Rating & USP Certified.

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product profiles

Legend

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SISU To Go Ester-C ® Energy Boost Ester-C® Energy Boost is a daily vitamin drink mix that mixes easily in water and provides a healthy, natural alternative to pre-bottled drinks. Each convenient packet contains 1,000 mg of clinically-proven, immune-boosting Ester-C® vitamin C and energizing B vitamins, minerals, and electrolytes. Available in natural orange, wildberry or new lemon-lime flavour.

Pascoleucyn Inositol SAP Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory disorders and female infertility. Signs and symptoms of PCOS may include anovulation or menstrual irregularities; ovarian cysts on ultrasound; hyperandrogenism including hirsutism, acne and alopecia; insulin resistance; and obesity. Myo-Inositol has been suggested as a first-line therapy in the treatment of PCOS, and has been shown to be effective in mitigating the symptoms of this syndrome and its associated comorbidities.

A non-specific immune remedy that increases the body’s natural defenses in acute and chronic infections. It relieves symptoms due to colds and flu such as headaches, stuffy nose, sore throat, cough and fever. A prophylactic intake of PASCOLEUCYN® can give your patients broad protection against colds and flu. Recommend the ampoules once or twice per season for general defense, and the drops when others around your patient are starting to get sick.

Cyto-Matrix - Omega-D3 Liquid Forte Evidence based dosages for all indications; High safety profile; Molecularly distilled, ultrapure fish oil; Easy to administer for maximum patient adherence; No fishy aftertaste, light citrus flavour. Each teaspoon (5 mls) contains: Fish Oil Concentrate - 4,377 mg; Omega-3 Fatty Acids 2,845 mg, EPA (Eicosapentaenoic acid) - 1,750 mg; DHA (Docosahexaenoic acid) - 875 mg; Vitamin D3 -1000 IU.

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Product MonograPh Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. Without treatment, AGA is progressive, and causes social distress in many affected men and™women (Sinclair 1998). Bio-Fen Plus contains extracts METAGENICS STROVERA of fenugreek seeds, saw palmetto berries and flax lignans, as well as specificEvitamins. Each ingredient is known to possess inhibitors of the enzyme 5α-reductase. These inhibitors are responsible for relieving symptoms associated with hereditary AGA. One of the primary causes of hair loss is a high level of the male hormone dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001). For people with AGA, their follicles have a greater number of androgen receptors to which DHT attaches. 5-α-reductase catalyzes the enzymatic conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998).

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Vitamins Saw palmetto (Serenoa repens) Estrovera by Metagenics features a special extract of Siberian rhubarb root (Rheum rhaponticum) designed to reduce hot flashes and other menopausal symptoms In a Polish study of 46 women who had symptoms of diffuse alopecia, calcium Standardized (lipophillic) Serenoa extract has been found to be a potent inhibitor without potential serious adverse events associated with conventional hormone therapies (HT). pantothenate was orally administered twice a day in doses of 100 mg for four to of 5α-reductase, resulting in decreased tissue DHT. An open-label, dose response months, and B6 was injected every[1]. dayInfor to 30 days andthe repeated study was conducted on 42 healthy males to menstruation determine thehas effect of afor combination Menopause is the clinical term used after ceased one year, afterfive which women arevitamin considered postmenopausal the20Western world, again after six months It was determined of age carotenoid and sawispalmetto berry with lipid51extract on median DHT and range forastaxanthin natural menopause 40 to 58 years, being the age for menopause. The average(Brzezińska-Wcisło age of menopause 2001). in Canada is also 51, and itthat is vitamin B6 administered parenterally foralla the fewmenopausal weeks induces improvement in the hair testosterone (Angwafor 2008). The men were divided into two groups: estimated levels that women over age 50 will comprise almost one quarter (22%) of the population by the year 2026 [2]. Of symptoms, hot flashes condition in women a subsetinofWestern women countries and reduces hairfrom loss.hot flashes, with 30% one(also group received anddebilitating. the other Nearly referred to as800 hot mg/day flushes) of arethe the combination most commonsupplement and potentially 80% of suffer group received mg/day thefrequent supplement for 14 days. ANOVA-RM showed reporting hot2000 flashes severeofand enough to seriously affect quality of life [3]. significant within-group increases in serum total testeosterone and significant Medicinal Ingredients dose Per capsule decreases in serum the DHT baseline in both dose option groupsfor(P=0.05). There HT is considered mostfrom effective medical treatment relief of hot flashes and other menopausal symptoms [4]. However, HT is currently recommended for moderate to severebetween vasomotor symptoms due toregard potential increased cancer, cardiovascular events and other unwanted side effects [1]. The wasonly no significant difference dose groups with to the increaserisk of of breast Fenugreek (Trigonella foenum graecum) 260 mg and North American Menopause Society recommends usingwere the lowest possible dose for the shortest duration possible [3]. The Society for Obstetricians testeosterone or the decrease of DHT; therefore both doses effective (Angwafor seed extract 4:1 Gynaegologists of Canada also recommends using the lowest effective dose for HT [2]. Women with a history of cardiovascular events, venous thromboembolism, 2008). breast or uterine cancer, or liver disease, should not use estrogen to alleviate vasomotorSaw symptoms [1]. berry extract containing palmetto 160 mg Another study tested liposterolic extract of Serenoa repens (LSESr) and beta45% free fatty acids Among the natural non-pharmalogical therapies, phytoestrogens are the most popular and the most studied category. Phytoestrogens are plant substances found in sitosterol in the treatment of males (23-64 years of age) with mild to moderate AGA. clover, flax, hops, others, that possess by bindingFlax to estrogen receptors (ER). However, lignans, standardized to 20%systematic review of literature found Six soy, of 10red(60%) subjects wereand rated as improved at theweak finalestrogenic visit, thus activity establishing 100 mg that phytoestrogens such as isoflavones, lignans, and 8-prenylnaringenin have, at best, secoisolariciresinol only modest effect in ameliorating symptoms [5-7]. diglucosidemenopausal (SDG) the effectiveness of 5α-reductase inhibitors against AGA (Prager 2002). Chronic inflammation of the hair follicle is considered to be a contributing factor for AGA. A Since 1993, a special phytoestrogen extract from the root of Siberian rhubarb (Rheum rhaponticum) known in scientific literature D-calcium pantothenate (Vitamin B5) as ERr 731™ 10.40has mgbeen study by Chittur etbyalhealthcare sought to practitioners determine whether blockade of inflammation using and related complaints [8]. Unlike Chinese rhubarb (e.g., R. palmatum, R. recommended in Germany for menopausal hot flashes LSESr and two anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg officinale) or other medicinal rhubarb species that contain strong laxatives anthraquinones, the main constituents of ERr 731 are hydroxystilbenes, including therhaponticin, expression ofdesoxyrhaponticin, molecular markersrhapontigenin, of inflammation 2009). It was[8]. found and(Chittur desoxyrhapontigenin They are found to be agonists of estrogen receptor β (ERβ) and do not display ERα HCl (Vitamin B6)of hot flashes [10]. In2 tissues mg that express both thatactivity the combination suppressed gene expression of in thePyridoxine in endometrial tissue in lipopolysaccharide-activated laboratory studies [9]. ERβ activation is involved estradiol-mediated reduction chemokines associated withaspathways involved in inflammation and protection apoptosis. against ERα-mediated effects in the breast and endometrium [11, 12]. ERα and ERβ, ERβ acts a negative regulator of ERα and offers Riboflavin (Vitamin B2) 1.58 mg The study concluded that 5-alpha reductase inhibitors in combination with Clinical have demonstrated 1 tablet (4 mg) dailytwo-pronged of ERr 731 offers effective Folic relief for common menopausal symptoms, including0.095 hot flashes blockade oftrials inflammatory processes that could represent a new approach acid mg [8, 10, 1315].treatment For example, in a multicenter, randomized, placebo-controlled clinical trial in which 112 perimenopausal women with menopausal symptoms received either 1 in the of AGA. tablet of ERr 731 (n=56) or placebo (n=56) for 12 weeks, ERr 731 treatment comparedBiotin with placebo treatment resulted in [15]: 400 mcg Fenugreek• SeedsA significant reduction of the Menopause Rating Scale (MRS) total score and in each individual MRS item score significant reduction in the number hot flashes, fromflavonoids an average of 12 per day at baseline to 2.8 ±2.8 (mean ± SE) per day at 12 weeks non-Medicinal Ingredients Fenugreek•seeds Acontain 5% to 30% protein, steroid of saponins, sterols, • A significant reductionand in the hot flashSteroid weekly saponins weighted score and alkaloids (notably trigonelline choline). bind and Inert microcrystalline cellulose and vegetable-based magnesium eliminate extra cholesterol and hormones in the body; DHT is made from in a veggie-based capsuleto help improve quality of life In a long-term clinical study with subjects taking ERr 731 for up to 24 months, womenstearate reported continued symptom reduction testosterone, which is in turn is made from cholesterol. Therefore, when excess through reduced anxiety, negative mood, and sleep disturbances [10]. cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 Recommended adultare dose: One capsule day adults 12.5g andalso 18.0g of that germinated seed powder Datawho fromconsumed these clinical trials show ERr 731fenugreek is well tolerated; no ERrfor 731-related adverse events observed. [8, 10,per 13-15] one month, higher levels of consumption resulted in a significant reduction in total cholesterol lipoprotein (LDL) islevels (Sowmya 1999). practitioners in North America, exclusively from Metagenics, Inc. ERr 731,and the low-density active ingredient in Estrovera, available to healthcare

Flax lignans Flax Estrovera reduces theingredients amount of (per DHT1 tablet) produced by reducing cholesterol levels6. in the Lethaby AE, et al. Phytoestrogens for vasomotor menopausal symptoms. body.Medicinal A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed Cochrane Database Syst Rev. 2007;(4):CD001395. ingredient: Rhapontic Rhubarb 4 mg 7. (Pan Clarkson TB, et al. The role of soy isoflavones in menopausal health: report of significantly reduces circulating total (rheum rhaponticum root) ERr 731and LDL-cholesterol concentrations The North American Menopause Society/Wulf H. Utian Translational Science 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L Non-Medicina ingredients: Symposium in Chicago, IL (October 2010). Menopause. 2011;18:732-753. (95%Microcrystalline CI: -0.20, 0.00 cellulose, mmol/L) stearic and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), acid 8. and Heger M, et al. Efficacy and safety of a special extract of Rheum rhaponticum respectively. Significant reductions were observed with whole flaxseed (-0.21 (vegetable), croscarmellose sodium, silica, (ERr 731) in perimenopausal women with climacteric complaints: a 12-week -0.16and mmol/L, and lignan enteric respectively) coating (deionized water, (-0.28 and -0.16 mmol/L, respectively) randomized, double-blind, placebo-controlled trial. Menopause. supplements 2009). cellulose(Pan acetate phthalate, glycerol

2006;13(5):744-759. Wober J, et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. J Steroid Biochem Mol Biol. 2007;107(3-5):191-201. Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J 10. Hasper I, et al. Long-term efficacy and safety of the special extract ERr 731 of Int Soc Sports Nutr 2008;5:12. Rheum rhaponticum in perimenopausal women with menopausal symptoms. References Brzezińska-Wcisło L. Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Menopause. 2009;16(1):117-131. Lek1. 2001;54:11-8. Nelson HD. Menopause. Lancet. 2008;371(9614):76011. Frasor J, et al. Response-specific and ligand dose-dependent modulation of 770.B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes estrogen Chittur S, Parr using a composition containing thioctic acidin and palmetto extract. Evid Based receptor (ER) alpha carnitine, activity by ERbeta thesaw uterus. Endocrinology. 2. Society ofMed Obstetricians and Gynaecologists of Canada. Complement Alternat 2009. 2003;144(7):3159-3166. Canadian Consensus Conference on Menopause, 2006 Lindberg MK, et on al. blood Estrogen receptor (ER)-beta reduces ERalpha-regulated Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects12. of flaxseed interventions lipids. Am J Clin Nutr 2009;90:288-97. Update. J Obstet Gynaecol Can. 2006;28:S1-S112. gene transcription, supporting a "ying yang" relationship between ERalpha and 3. N, Bickett Umland Treatment strategies for reducing the Prager K, EM. French N, Marcovici G. A randomized, double-blind, placebo-controlled trial toindetermine the Endocrinol. effectiveness of botanically derived inhibitors of 5-alpha-reductase in the ERbeta mice. Mol 2003;17(2):203-208. treatment of androgenetic alopecia. J Altern Complement Med 2002;8:143-52. burden of menopause-associated vasomotor symptoms. J 13. Kaszkin-Bettag M, et al. Efficacy of the special extract ERr 731 from rhapontic Manag Care Pharm. 2008;14(3 Suppl):14-19. Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9. rhubarb for menopausal complaints: a 6-month open observational study. Altern 4. North American Menopause Society. The 2012 hormone Ther Health Med. 2008;14(6):32-38. Sinclair R. therapy Male pattern androgenetic alopecia. BMJ 1998;317:865-9. position statement of: The North American 14. Kaszkin-Bettag M, et al. The special extract ERr 731 of the roots of Rheum Menopause Society. Menopause. 2012;19(3):257-271. Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods anxiety Hum Nutr 1999;53:359-65. rhaponticum decreases and improves health state and general well-being 5. Coon JT, et al. Trifolium pratense isoflavones in the in perimenopausal women. Menopause. 2007;14(2):270-283. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87. treatment of menopausal hot flushes: a systematic review 15. Kaszkin-Bettag M, et al. Confirmation of the efficacy of ERr 731 in meta-analysis. Phytomedicine. 2007;14(2-3):153Vierpper H,and Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone inperimenopausal healthy men and women and in men with male pattern baldness: stable isotope/ women with menopausal symptoms. Alterndetermination Ther HealthbyMed. dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4. 159. 2009;15(1):24-34. triacetate, ammonium hydroxide, hypromellose, maltodextrin, and polyethylene glycol). References

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cover story

Dr Kristy Prouse,

MD, FRCSC Institute for Hormonal Health By Philip Rouchotas MSc, ND Photography by Robyn Russell IHP has had the privilege of interviewing what has now been dozens of conventionally- trained physicians who at some point in their career make the decision to adopt integrative systems of practice. Each of these stories unfolds with unique circumstances, yet they all seem to share a stunning number of similarities. Dr Kristy Prouse, MD, FRCSC is a welcomed addition to the growing list of conventionally- trained Canadian physicians finding answers to difficult medical questions among the trainings of integrative healthcare providers.

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cover story

From left to right: Dr. Andrea Kuzmiski ND, Kristina Graham HN, Michelle Armstrong CPT, Dr. Kristy Prouse MD, FRCSC, Ashna Starrett HHP, Camille Lawson RN

A

fter many years of conventional practice as an OBGYN, performing several thousand deliveries and gynecological surgeries, Kristy felt she was lacking adequate tools to help a large and growing number of her patients. Training that included bioidentical hormone therapy, an understanding of the concept of adrenal fatigue, nutrition and nutraceutical science, and herbal medicines has seen her transform her career into something her colleagues from the past remain confused by. Welcome to the practice of integrative medicine Kristy. As yet another conventionally- trained physician we interviewed once stated “once you start using this type of medicine, you find yourself ethically unable to go back”. Dr Prouse began her academic training in 1998 with a degree in Psychology from Western University. She obtained a second undergraduate degree in Genetics and Cell

Biology from the University of Toronto, then went on to complete medical training at Queen’s University. In 1988 Kristy began her medical residency at the University of Calgary in Obstetrics and Gynecology, where she received the Laparoscopic Surgery Award of Excellence. In 2002 Kristy entered her first practice, in Orillia, Ontario. This “smaller” town setting was a general OBGYN practice. Two years later, Kristy moved to the Trillium Health Centre in Mississauga, to be closer to her ailing mother. She maintained her position at the Trillium Health Centre, and simultaneously took on roles of Associate Professor at the University of Toronto School of Medicine and the Northern Ontario School of Medicine. Kristy maintained her role at the Trillium Health Centre until October of 2011, opening the Institute for Hormonal Health, in Oakville, Ontario, in November of 2011.

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What led this well- decorated, successful, mother of twin 11 year old girls, OBGYN to leave the Trillium Health Centre in favour of opening her own model of integrative health centre? As has often been the case, Dr Prouse’s story begins with a personal health crisis. “There was a lot happening at once... the demands of practice at the Trillium centre... frustration with aspects of the care I was providing people... feeling I didn’t have good answers for a lot of the concerns my patients had... Then realizing I was in need of the same solutions my patients were seeking! By early 2011, I was simply burnt out! I started thinking of ways to manage my situation, but did so not knowing a different medical model may have a solution for me. My answers were to consider practicing half time, perhaps bringing a colleague on board to share a practice with, and I was even considering outright retirement”. Kristy goes on to describe “after having considered visiting an integrative healthcare provider for some time, a set of unique circumstances arose where a specific integrative healthcare provider was suggested to me as someone to see on four separate occasions within a 48 hour period! I was diagnosed as having “adrenal fatigue”... I felt better within days of initiating treatment”. This personal journey led Kristy to dedicate countless hours to literature- based research on the concept of adrenal fatigue, which then spurred interest in the much larger spectrum of practice that comprises integrative medicine. Kristy felt that what she was finding was the solution to the many problems she had seen in years of practice as an OBGYN that she had no solution for. She described a sense of the system of practice being much more in alignment with her person... “alignment with what I was meant to be doing”... Since making the transition to an integrative system of practice Kristy feels renewed. “Recognizing patterns in history and physical examination as well as implementing objective testing has me using my brain in a way I haven’t in years! The most rewarding part however is effecting significant change for many people who are seeking our help after exhausting their options in the conventional system and after being told that there is nothing wrong with them.” www.ihpmagazine.com l October 2012 35

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cover story

Kristy has managed to assemble an incredible team of integrative healthcare providers, each brining a unique skillset to complement the team as a whole. Dr Andrea Kuzmiski, ND, a 2004 graduate of the Canadian College of Naturopathic Medicine, certified in parenteral therapy, is described as a key member of the team. Among the broad

“I was diagnosed as having ‘adrenal fatigue’ ... I felt better within days of initiating treatment.” set of skills Andrea is able to showcase in the facility, Kristy highlights the immense value of parenteral therapies, especially for what is described as advanced stages of adrenal fatigue. The Institute for Hormonal Health team also includes Kristina Graham, holistic nutritionist, Michelle Armstrong, personal trainer and wellness counselor, Ashna Starett, holistic health practitioner, and Camille Lawson, sex therapist.

Many centres of integrative healthcare attempt to duplicate the IHH model of care delivery, yet most fail to do so. Jennine Le Tendre acts as the patient care coordinator. A patients first and second visit are booked with Dr Prouse. A portion of these visits is OHIP covered, dealing with the taking of the case history and physical exam. There is also a fee for service for patient visits, as well as fees for integrative tests performed, etc... Integrative testing is often recommended, the specific test(s) chosen based on the case presentation. The second visit with Dr Prouse provides an opportunity for the patient to review the findings of the intake, physical exam, and results of integrative testing, and to decide upon the best course of treatment. Jennine plays a vital role serving as the patient’s point of contact, educating patients as to the use of integrative diagnostic test kits, and coordinating future patient visits to the team members best suited for the specific case in question. The IHH achieves a truly integrative model of care, with Kristy serving as the medical coordinator and Jennine serving as the patient coordinator for each case.

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I asked Kristy about the reaction of her colleagues to the news that she would be leaving the Trillium Health Centre to open a private integrative medical practice. She replied “they were supportive and excited for me, but somewhat uninterested in what I was going to be doing”. That got me thinking... I have met many hundreds, thousands in fact, of conventionally- trained MD’s who have never read a thing about integrative medicine, but are convinced it is a useless practice. Each and every MD who spends even 10 hours reading about integrative medicine invariably ends up at the same place; reading more about integrative medicine. And after enough hours of reading, such MD’s either practice integrative medicine themselves, or partner with integrative healthcare practitioners to make such care available to their patients. So we seem to be evolving to a solution... We need to expose MD’s to evidence pertaining to integrative medicine... “One MD at a time” seems to be working quite well, as the number of conventionally- trained MD’s taking up practice as integrative healthcare providers is growing exponentially. It seems we are approaching a tipping point... How long can it possibly be until true integrative medicine makes its way into medical school curriculums? IHP is grateful to Dr Kristy Prouse and the entire Institute for Hormonal Health team for taking the time to allow us to showcase their efforts to you. A conventionally- trained OBGYN felt the care she was providing was lacking, improved her own health through visits to an integrative healthcare provider, and subsequently evolved her own career to mirror the lessons she learned through research and a personal healing journey. After five years of delivering IHP this is somewhat of a broken record, yet one we love hearing over and over again. ■

THE INSTITUTE FOR HORMONAL HEALTH

Dr Kristy Prouse, MD, FRCSC: Clinic Director Dr Andrea Kuzmiski, ND: Naturopathic Doctor Kristina Graham, RHN: Holistic Nutritionist Michelle Armstrong, CPT: Wellness Counselor/ Personal Trainer Camille Lawson, RN: Sexuality Therapist Ashna Starrett: Holistic Health Practitioner Jennine Le Tendre: Patient Care Coordinator Brittany Dell: Reception

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Progressive MultiVitamins are designed with you and your patients in mind. They have been formulated and balanced by Dr. Mikhael Adams to include the right ingredients and dosages, along with age, gender and activity specific nutrients that make Progressive the smarter choice.

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PRODUCT MONOGRAPH Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. PROGRESSIVE NUTRITIONAL SUPPLEMENTS MULTIPLE VITAMINS & MINERALS Without treatment, AGA is progressive, and causes social distress in many affected men and women (Sinclair 1998). Bio-Fen Plus contains extracts BIO-FEN for Men and Women The Progressive family offers age, gender, and activity specific vitamin and mineral formulas. Each formula is designed specifically to target of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme the unique nutritional demands throughout a lifespan. 5α-reductase. are responsible for relieving symptoms associated withPlus hereditary AGA. Bio-Fen represents aThese line of inhibitors products approved by Health Canada for hair growth and restoration. Bio-Fen for Men and Bio-Fen Plus for Women are both oral natural health Multiple Vitamins Minerals the Maintenance Good Healthalopecia One of the primary causes ofgrowth hair loss isinand a high level of hereditary the of male hormone dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001). products (NHPs) which support hairand in men women with androgenic (AGA), or female/male pattern baldness. Bio-Fen contains a combination of herb extracts and vitamins & minerals that arethe known inhibit the enzymeof 5supplement -reductase (5AR), a keyfunction pathway implicated in the progression of AGA. Vazir, etAGA, al (2006) evaluated effect of a micronutrient on mental childrenattaches. (aged 6 –5-α-reductase 15 years). Thiscatalyzes double blind, For people with their follicles have atogreater number androgen receptors to whichin DHT the enzymatic placebo-controlled, matched-pair, cluster, randomized trial assessed a cohortfive-fold of 608 children for intelligence, and concentration, conversion of testosterone to dihydrotestosterone, which binds to the receptor more avidly than theattention parent compound (Sinclair 1998). AGA Pathophysiology memory, and school achievement, before and after 14 months of micronutrient supplementation. Results indicated that supplementation One of the primary loss is a high significantly level of the male hormone, dihydrotestosterone (DHT) the hair (Hoffmann 2002).aged DHT6is– produced with acauses rangeofofhair micronutrients improved attention-concentration overwithin the period of follicle 14 months in children 15 years.from Saw palmetto repens) testosterone in the(Serenoa testes (males), the adrenal glands, and the follicle. After a period of time, anVitamins over abundance of DHT causes the hair follicle to degrade and shortens the active Increasing bone mineral content (BMC) duringtoperiods ofThere rapid (childhood & may effectively prevent osteoporosis and phase of the hair, eventually leading to thinning hair and eventual hair isgrowth a familial tendency foradolescence) stepwise the hair follicle and an increase in the calcium ratio In a Polish study of miniaturization 46 women whoof had symptoms of diffuse alopecia, Standardized (lipophillic) Serenoa extract has been found be loss. a potent inhibitor age-related loss. Shatrugna, et al (2006) effectand of alocal micronutrient supplementation BMC, andonly bone of of telogen (resting phase) tobone anagen (growth phase)DHT. hairs, which isinvestigated promoteddose by the systemic effects of was androgens. Althou ghon everyone produces thosemg with pantothenate orally administered twicebone a dayarea, inDHT, doses of 100 fora four to 5α-reductase, resulting in decreased tissue An open-label, response mineral density (BMD)inat variousfollicles, sites in binding childrensites (aged 6 – 16and years). The micronutrient supplement was found to increase tissue higher of androgen their fora DHT, greater androgen sensitivity experience hairinjected loss (Prager 2002). 5AR istogrowth responsible forrepeated the 30 days and five months, and vitamin B6increases was every dayoffor 20femur. studynumber was conducted onreceptors 42 healthy maleshair to determine the effect of combination skeletaltoshell in apparently normal children over a 14-month period, including site-specific BMD at the neckTrueb the conversion of and testosterone dihydrotestosterone, which binds to the same androgen receptor, but with five-fold greater affinity. (Hoffmann 2002, 2002)

of carotenoid astaxanthin and saw palmetto berry lipid extract on DHT and

again after six months (Brzezińska-Wcisło 2001). It was determined that vitamin

SHEEP study examined themen association between thetwo usegroups: a multivitamin supplements parenterally and the risk for of myocardial infarction Results in the hair B6 administered a few weeks induces(MI). improvement testosteroneThe levels (Angwafor 2008). The were divided into Flax were based data from a large population-based, case-control study ofcondition subjects aged 45 – 70 years. The included 1296 cases (910 subset women andstudy reduces hair are loss. onelignans groupinhibit received 800onmg/day of the combination supplement the other Flax the enzyme 5AR, thus balancing formation of the maleand hormones that are responsiblein fora hair lossof(Evans 1995). Flax lignans converted by the body to men,2000 386 mg/day women)ofwith asupplement first nonfatal 1685 controls (1143 men, 542 women) frequency-matched to the cases by sex, age and group received forMI 14and days. ANOVA-RM enterolactones, which compete with the estrogen and testosterone for receptor binding,showed and increase sex hormone binding globulin (SHBG), resulting in lower levels of free (ie active) hospital catchments areain(Holmquist, et testeosterone al 2003). The and results from this study indicate that use of a multivitamin supplements may aid in the significant within-group increases serum significant estrogen and testosterone. Flaxseed has been shown total to reduce serum levels of 17-beta-estradiol and estrone sulfate (Hutchins 2001), and results in a shift in estrogen metabolism to primary prevention of MI. Medicinal Ingredients Dose Per Capsule decreases serum DHT baseline in both favor the lessin biologically activefrom estrogens (Brooks 2004).dose groups (P=0.05). There was no significant difference between dose groups with regard to the increase of The elderly are an epidemic of deficiency, and multivitamins and minerals are extremely(Trigonella helpful in reducing of a variety of diseases in Fenugreek foenum risk graecum) Fenugreek 260inmg this by Girodon, et al (1997)(Angwafor examined the impact of trace 4:1 element and vitamin supplementation 81 elderly testeosterone orpopulation. the decreaseAofstudy DHT;conducted therefore both doses were effective seed extract Fenugreek has been used traditionally as an oral and topical treatment for hair loss. Plant sterols contained in fenugreek such as -sitosterol have beendeficiencies. shown to block DHT subjects over a 2-year period. Before supplementation more than 2/3 of the elderly subjects were found to have significant 2008). receptor sites (Prager 2002, see below). After only 6 months of supplementation, significant increases in these vitamins minerals wereextract observed. Furthermore, a160 200% Sawand palmetto berry containing mg reduction inliposterolic infectious disease subjects administered multivitamin was demonstrated. Another study tested extract incidence of Serenoaamong repenselderly (LSESr) and beta45% free fatty acids Saw Palmetto (men’s product) sitosterol inAgeing the treatment of males (23-64 years of age) with mild to moderate AGA. with in micronutrient intake,tissue making malnutrition an increasing public health the elderly. Saw palmetto extract isisaassociated potent inhibitor ofa 5reduction -reductase, resulting in decreased DHT (Prager 2002). In a pilot study of 26 men problem with mildamong to moderate AGA, treatment with Flax lignans, standardized to 20%found Six of 10 (60%) subjects were rated asextract improved at and the final visit, thus50mg establishing Grieger, et alsaw (2007) examined the use of abeta-sitosterol multivitamin supplement forsymptoms 6 months 92toelderly Itblinded was that multivitamin a combination of lipophilic palmetto 200mg improved byinup 60%, assubjects. scored by assessors (Prager 2002). In a meta 100 mg diglucoside (SDG) improved micronutrient status in vulnerable may of reduce the risk of micronutrient-related diseases. the effectiveness of 5α-reductase inhibitors AGA (Prager 2002). Chronic analysis by thesupplementation Cochrane group, saw palmetto hasagainst also been found to this be effective as a population, treatment secoisolariciresinol forwhich symptoms BPH (Wilt 2002). to havefactor a positive effect Multivitamin also inflammation of the hairsupplementation follicle is considered toappeared be a contributing for AGA. A on bone quality, which may also reduce the risk of osteoporosis. D-calcium pantothenate (Vitamin B5) 10.40 mg Silica (women’s product) study by Chittur et al sought to determine whether blockade of inflammation using Silica is a and traceDosage mineral that has been found to increase hydroxyproline concentration in connective tissue (Barel 2005). In a randomized, double blind, placebo controlled study, 50 LSESr two anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg Indication: in the maintenance of good health. women with damaged skin Aids weremarkers treated orally with 10mg silica as orthosilicic the expression of molecular of inflammation (Chittur 2009). It acid was (OSA) found daily for 20 weeks. The treatment group reported a significant decrease in visual analog controlled trial conducted in 50 women with brittle hair found that 10mg silica as OSA scale ratings ofProgressive hair brittleness (Barel 2005). A second Multiple Agerandomized, double blind, placebo Dosage Pyridoxine HCl (Vitamin B6) 2 mg that the combination suppressed lipopolysaccharide-activated gene expression of for 9 months significantly improvedFormula hair elasticity, breakage, and diameter (thickness) (Wickett 2007). Vitamin & Mineral chemokinesKids associated with pathways involvedChildren in inflammation and apoptosis. (4 – 8 years) ChewRiboflavin ½ tablet with breakfast a total (Vitamin B2)and ½ tablet with dinner for 1.58 mg of study thatcell 5-alpha inhibitors in combination withmetabolism. B The vitamins are concluded support healthy growthreductase and division, and facilitate optimal hormone one tablet daily. blockade of inflammatory processes could represent a new two-pronged approach Adolescents (9 – 18 years) ChewFolic one tablet for amg total acid with breakfast and one tablet with dinner 0.095 Medicinal ingredients per capsule in both the men’s and women’s: in the treatment of AGA. of two tablets daily. Fenugreek (Trigonella foenum graecum) seed extract 4:1 ....................................................260 Biotin mcg Takemg one capsule with breakfast, lunch, and dinner, for400 a total of Active Women (19 – 50 years) Active Women (dry equiv FenugreekActive Seeds three capsules daily. Active Men (19 – 50 years) Men1040mg) Flax lignans, standardized to 50% SDG ...............................................................................100 mg Non-Medicinal Ingredients Fenugreek seeds contain steroid saponins, sterols, flavonoids (19 – 50 years) Adult Women 5% to 30% protein, Women d-calcium pantothenate (Vitamin B5) ..................................................................................10.4 mg and alkaloids trigonelline and choline). saponins bind and Men (19Steroid – 50 years) Adult(notably Men Niacinamide (Vitamin B3) ...................................................................................................10.3 mg Inert microcrystalline cellulose and vegetable-based magnesium Women (19 – DHT 50 years) one tablet with breakfast, lunch, and dinner, for a total of three Adult Women eliminateHCl extra cholesterol and hormones in the body; is made fromChew mgstearate Pyridoxine (Vitamin B6)(Chewable) ...............................................................................................2.0 tablets daily. in a veggie-based capsule Men (19 – 50 years) Adult Men (Chewable) testosterone, which is in turn is made from cholesterol. Therefore, when excess Riboflavin (Vitamin B2) .......................................................................................................1.6 mg Women (≥ 50 years) Take one Women 50 Plus cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 Folic acid ..............................................................................................................................95 mcg capsule with breakfast, lunch, and dinner, for a total of capsules daily.adult dose: One capsule per day Men (≥ 50fenugreek years) seed powder forthree 50 Plus12.5g and 18.0g of germinated Recommended adults....................................................................................................................................250 whoMen consumed Biotin mcg

one month, higher levels of consumption resulted in a significant reduction in total

Interactions Men’s also has: cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999). dose each vitamin & mineral is included above the minimum mg dosage value and at or below the maximum dosage value as Saw palmetto The berrydaily extract 4:1 of .............................................................................................125 established the Natural Health Products Directorate (NHPD). The general combinations of vitamins, minerals, and herbal components (dry equiv. 500by mg) Flax lignans are safe (NHPD monograph: Multi-Vitamin/Mineral Supplement). Flax reduceshas: the amount of DHT produced by reducing cholesterol levels in the Women’s alsoDue to potential toxicity from some of the vitamins, minerals and herbal components, children under 19 years of age are not recommended body.(silicon A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed mg Silicon ........................................................................................................40 todioxide) take any of the adult specific formulas (NHPD monograph: Multi-Vitamin/Mineral Supplement). significantly reduces circulating total and LDL-cholesterol concentrations (Pan mg Iron (ferric citrate) ................................................................................................................20 Due to the potential of toxicity and adverse effects of some of the vitamins, minerals and herbal components, none of the formulas are 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L recommended for use in pregnant or breastfeeding women (NHPD monograph: Multi-Vitamin/Mineral Supplement). Recommended use:0.00 one mmol/L) capsule twice capsules perCI: bottle). Bio-Fen® Plus capsules are usually effective (95% CI: -0.20, and daily 0.08 (60 mmol/L (95% -0.16, 0.00 mmol/L), Some of the the vitamins, and herbal components may interact diseases and conditions, and/or lab test results. It is at respectively. stopping hair loss within first twominerals, months. Anyone experiencing new growth see itmedication, within four months. Significant reductions were observed with whole flaxseed (-0.21should and with recommended that all ingredients be reviewed before use in an individual under medical taking prescription medication, Once Bio-Fen is stopped, the hairand growth pattern will and slowly return to its original point, however some peoplesupervision, may -0.16 mmol/L, respectively) lignan (-0.28 -0.16 mmol/L, respectively) suffering a serious and/or pre-existing medical condition (NHPD monograph: Multi-Vitamin/Mineral Supplement). be able to continue with from a lower maintenance dose.

supplements (Pan 2009).

Quality Assurance Bio-Fen has been approved by Health Canada and has received a unique NPN number. In additionReferences to being approved Test Specifications Girodon F, et al (1997). Effect of micronutrient supplementation on for hair growthParameter applications, Bio-Fen has been approved for additional health benefits. infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Microbial 41(2):on98-107. Angwafor F Total III, Anderson response study to than determine thecfu/g effect of a dietary Metab, supplement dihydrotestosterone, testosterone and estradiol levels in healthy males. J Count ML. An open label, dose USP Less 5,000 Grieger JA, et al (2007). Effect of multivitamin on vitamin D status and Int Soc Sports Nutr 2008;5:12. Contraindications: The ingredient combination in Bio-Fen Plus Men/Women most adults. Yeast & Mold USP Lessfor than 100 cfu/g is generally safe heelfor ultrasound bone density in Australian aged care residents. Bio-Fen should not be used coli by patients withB6 diabetes, or known hypersensitivity to any ingredients. USP Negative Brzezińska-Wcisło L. Evaluation of vitamin and calcium pantothenate effectiveness on hair growth International from clinical Congress and trichographic aspects for treatment of diffuse alopecia in women. Wiad Escherichia Series, 1297: 109-119. Lek 2001;54:11-8. Holmquist C, et al (2003). Multivitamin Supplements Are Inversely USP Negative Salmonella sp Associated with Risk of Myocardial Infraction in Men and Women – References USP Staphylococcus aureus of inflammatory Chittur S, Parr B, Marcovici G. Inhibition geneNegative expression in keratinocytes using a composition carnitine, Program thioctic acid and saw palmetto Stockholm containing Heart Epidemiology (SHEEP). J Nutr, 133:extract. 2650- Evid Based Brooks JD, et Heavy al. Am JMetal Clin Complement Alternat Med Nutr. 2009. 2004 Feb;79(2):318-25. 2654. Evans BA, et al. 1995 Nov;147(2):295-302. Arsenic USEPA < 1.0 ppm NHPD monograph. (2007). supplement, October 22. Pan A, YuR.D,Clin Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. AmMulti-vitamin/mineral J Clin Nutr 2009;90:288-97. Hoffmann Exp Dermatol. 2002 Jul;27(5):373-82. Shatrugna V, et al (2006). Effect of a micronutrient supplement on health Cadmium USEPA < 0.5 ppm 2001;39(1):58-65. Hutchins AM,et al.K, Nutr Cancer. and nutritional status of school children: bone health and body Prager N, Bickett French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the Lead USEPA < 1.0 ppm Prager N, etof al.androgenetic 2002 Apr;8(2):143-52. composition. Nutrition, 22: S33-S39. treatment alopecia. J Altern Complement Med 2002;8:143-52. Total Mercury USEPA < 1.0 ppm Vazir S, et al (2006). Effect of micronutrient supplement on health and Trüeb RM. Exp Gerontol. 2002 Aug-Sep;37(8-9):981-90. Chemical Serenoa repens Alternative Medicine Review 1998;3:227-9. nutritional status of schoolchildren: mental function. Nutrition, 22: S26Wickett RR, et almonograph. Arch Dermatol Res. 2007 Dec;299(10):499-505. S32. Pesticides USP Absent Wilt T et al. Database Syst Rev. 2002;(3):CD001423. Sinclair R. Cochrane Male pattern androgenetic alopecia. BMJ 1998;317:865-9. Solvents USP Conforms to limits Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87. Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

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clinic profile

W

e at IHP are pleased to introduce the innovative Mahaya Forest Hill Integrative Health clinic. This integrative clinic is a multi-disciplinary wellness centre located in the beautiful Forest Hill neighbourhood in Toronto, near St. Clair Avenue West and Avenue Road. It opened its doors in 2010 as an expansion of the original downtown Mahaya clinic and was taken over by new management in June 2012. Since that time, it has been run successfully and independently by its new owner and Clinic Director, Dr. Chris Habib, ND. After his graduation at the Canadian College of Naturopathic Medicine, Chris proceeded to become the first and only person in Canada to complete an accredited two-year research residency. Chris has always had a passion for promoting integrative medicine and saw this clinic as an opportunity to further his goal on a larger scale. Since the transition in ownership, Chris has made it his mission to provide the community with unparalleled integrative health services. The clinic treats all of its patients with the utmost respect and strives to ensure that every single patient receives the absolute highest quality of care. All aspects of the patient interaction are taken into consideration so that patients are provided with the best possible overall health experience. Mahaya Forest Hill is located on the ground floor of a house at the corner intersection of a residential street and St. Clair Avenue West, creating a cozy and professional atmosphere for patients. Free parking is available on-site and the clinic is easily accessible by TTC. There is also a dentist, an esthetician, a counsellor, and a psychotherapist working out of the same building. The clinic benefits from the traffic of these and neighbouring businesses, as well as the street traffic on St. Clair Avenue West. Mahaya Forest Hill is a proud member of the Toronto Midtown Business Association and connects with the business community by providing talks at By Philip Rouchotas MSc, ND â&#x20AC;˘ Photography by Brendan Zwelling local companies. They also connect with the community through a strong social media presence, including blogging, newsletters, Facebook, Twitter, and LinkedIn. Chrisâ&#x20AC;&#x2122; wife, Nicole Habib, works behind-the-scenes as the Marketing Director of the clinic, bringing with her marketing experience from the publishing industry.

Mahaya Forest Hill

Integrative Clinic

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clinic profile The strength of Mahaya Forest Hill lies in its unique team of diverse health care practitioners. The team currently includes six Naturopathic Doctors, three Registered Massage Therapists, two Chiropractors, one Osteopath, and one Acupuncturist. On any given day of the week, patients have access to a specialized team of practitioners who work together to provide optimal wholeperson treatments. All health teams include at least one Naturopathic Doctor who ensures long-term health and works with the patient to optimize diet, nutrition, lifestyle, and address any other health factors. Together, the practitioners also make certain that the body is working properly from a structural perspective and that any pain is treated effectively through a variety of therapies. Overall, the practitioners have a tremendous amount of education and also have additional training in some of the following areas: evidence-based medicine, women’s health, acupuncture, blood typing, Arvigo massage, homeopathy, orthotic assessments, doula training, manual lymph drainage, and combined decongestive therapy. Patients are often introduced to the clinic through one initial contact point, whether it be with an individual practitioner or through the clinic’s website. All practitioners offer free 15-minute consultations to discuss their services with prospective patients. After booking an initial visit and working with one practitioner, patients have the option to expand their health team. Practitioners are responsible for making sure their patients obtain thorough care and this usually entails going beyond their own scope of practice. As a result, the clinic incorporates specialized inter-referral forms so that the entire health team has full access to all pertinent health information. From that point, patients are able to schedule back-to-back appointments with different practitioners, which provides them with an extremely supportive health

experience. One specific goal of the clinic is to make this type of health care more accessible and so the clinic is open for extended hours Monday to Saturday. Patients can also take advantage of specific programs that are offered by the clinic. The various programs provide support through different life stages and through natural life transitions. These programs include the Healthy Breast, Healthy Conception, Detoxification, Facial Rejuvenation, Healthy Weight Loss, Healthy Menopause, Healthy Pregnancy, Optimal Prevention, and Cancer Care. The clinic includes a laboratory with state-of-the-art integrative diagnostics and a dispensing room. Both on-site and and off-site blood draws are available for patients. Mahaya Forest Hill utilizes Gamma Dynacare, Rocky Mountain Analytical, ImmunoLabs, and Metametrix among some of its lab service providers. The supplement dispensary consists of a wide variety of the highest quality nutraceuticals, botanicals, topical creams, and homeopathics from companies such as AOR, NFH, Seroyal, Thorne, EBI, Boiron, St Francis Herb Farm, Promedics, and Douglas Labs. In addition, the clinic also carries specially formulated tinctures by Etheric Herbals and a large collection of dried herbs and teas. Custom herbal formulas can also be created for patients to address their individual health needs. IHP would like to thank Mahaya Forest Hill for the opportunity to highlight this highly successful clinic. Having many practitioners in one facility does not in itsellf define a multidisciplinary practice; it is the interaction between the allied practitioners, and their ability to effectively manage patient care in a manner that maximizes the unique skillset of the specific practitioners. Mahaya Forest Hill has achieved an impressive balance in delivery of truly integrative and multidisciplinary healthcare. ■

CLINIC TEAM Dr. Chris Habib, BSc(Hons), ND: Doctor of Naturopathic Medicine, Clinic Director Dr. Christine Matheson, BA, ND: Doctor of Naturopathic Medicine Dr. Kate Whimster, BCom, MIFHI, ND: Doctor of Naturopathic Medicine Dr. Bronwyn Hill, ND: Doctor of Naturopathic Medicine Dr. Anita Kappukatt, ND: Doctor of Naturopathic Medicine Dr. Chris Roberts, ND: Doctor of Naturopathic Medicine

AT A GLANCE Mahaya Forest Hill Integrative Health 73 Warren Road, Suite 102 Toronto, ON M4V 2R9 Phone: 416-792-4400 info@mahayaforesthill.com www.MahayaForestHill.com

Dr. Albert Huang, DC: Chiropractor Dr. Jonas Eyford, DC: Chiropractor Benjamin Besse-Bergier, BSc, DO: Osteopath Akari Yokokawa, RMT, CDT: Registered Massage Therapist John Leung, RMT, CAMA: Registered Massage Therapist William McNiece, RMT: Registered Massage Therapist Yuval Blum, LAc, Dip. TCM: Licensed Acupuncturist Nicole Habib, BA, MA: Marketing Director Adriana Machado: Office Administrator Sandy Kwan, ND(cand): Office Administrator

42 www.ihpmagazine.com l October 2012

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Active constituents: Each stick packet contains: Vitamin C 1,000 mg, thiamine 0.38 mg, riboflavin 0.43 mg, niacinamide 5 mg, D-pantothenic acid 2.5 mg, vitamin B6 10 mg, vitamin B12 25 mcg, folic acid 30 mcg, zinc gluconate 2 mg, manganese 0.5 mg, chromium 10 mcg, magnesium 58 mg, phosphorus 160 mg, calcium 155 mg.

General information: Ester-C® brand vitamin C: Ester-C® calcium ascorbate is a non-acidic form of vitamin C. It also contains vitamin C metabolites that improve its retention in cells. Vitamin C in immune health: Vitamin C is highly concentrated in white blood cells and supports proper function of these cells. Evidence suggests that vitamin C helps reduce the duration and severity of common cold symptoms and that those under stress (particularly significant physical stresses associated with competitive sports) may reduce their risk of common cold by as much as 50% when vitamin C is used preventatively. In a randomized, placebo-controlled clinical trial, Ester-C® at a dose of 1,000 mg per day for 60 days was found to significantly reduce the incidence and duration of common cold symptoms vs. placebo. Vitamin C and tissue health: Vitamin C is required for the proper synthesis of collagen, the protein-based building block for much of the body’s tissues. Vitamin C and anemia: In the prevention and treatment of iron deficiency, supplementing with at least 200 mg vitamin C per 30 mg of iron significantly improves iron absorption. Vitamin C in cardiovascular health: A combination of vitamin C and vitamin E, over 6 years, has been shown to slow the progression of atherosclerosis in hypercholesterolemic men and women by 26-33%. 500 mg vitamin C can reduce CRP levels by 24% in those exposed to cigarette smoke (whether active or passive). Peripheral arterial disease has been associated with both lower levels of vitamin C and higher levels of CRP. The antioxidant properties of vitamin C may also be helpful in the prevention of cardiovascular disease by helping to protect the arterial wall from oxidative damage. In addition, the importance of vitamin C in proper collagen synthesis may be beneficial in maintaining healthy blood vessel walls. Vitamin C in eye health: Long term (10 years or longer) use of supplemental vitamin C, either alone or in a multivitamin, has been associated with a 60% reduction in risk of nuclear and cortical cataracts. In combination with zinc, beta carotene, and vitamin E, vitamin C has been found to significantly reduce the progression of age-related macular degeneration (AMD) and the loss of visual acuity in those with advanced AMD. The Ester-C® advantages Ester-C® has been shown to be less irritating to the GI tract of acid sensitive individuals than ascorbic acid. It remains in the white blood cells in higher concentration and for a longer period, and also has been shown to cause less ascorbic acid and oxylate output in the urine.

Doses and directions: Stir one packet into water or juice 1 to 2 times per day.

Therapeutic effects: Multivitamin/mineral supplement for the maintenance of good health.

Identity & Potency (per 9.2 g)

Quality Assurance Vitamin C (calcium ascorbate)

USP

1,000 mg

Riboflavin (riboflavin-5-phosphate)

USP

0.43 mg

Niacinamide

USP

5 mg

Pantothenic acid (calcium d-pantothenate)

USP

2.5 mg

Vitamin B6 (pyridoxine hydrochloride)

USP

10 mg

Thiamine (thiamine hydrochloride)

USP

0.38 mg

Folic acid (folate)

USP

30 mcg

Vitamin B12 (cyanocobalamin)

USP

25 mcg

Phosphorus (potassium phosphate)

USP

160 mg

Calcium (calcium ascorbate)

USP/ ICP

155 mg

Magnesium (magnesium carbonate, magnesium hydroxide)

USP/ ICP

58 mg

Zinc (zinc gluconate)

USP/ ICP

2 mg

Manganese (manganese gluconate)

USP/ ICP

0.5 mg

Chromium (chromium (III) polynicotinate)

USP/ ICP

10 mcg

References i ii

iii iv v

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000980 Van Sraten et al. Preventing the common cold with a vitamin C supplement: a double blind, placebo controlled survey. Advances in Therapy; 2002 May;19(3):151-159. J Circulation 2003 J Am Coll Nutr. 2004 Apr;23(2):141-7 Arch Ophthalmol. 2000 Nov;118(11):1556-63

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Arch Ophthalmol 2003;121:1621-4. Gruenwald et al. 2006. Safety and tolerance of Ester C compared with regular ascorbic acid. Advances in Therapy. 23(1):Jan-Feb:171-8 viii Bernal et al. Vitamin C uptake in white blood cells in vivo. 2006. Unpublished ix Wright et al. A human clinical trial of Ester C vs. L-Ascorbic acid. 1987. vi

vii

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The Journal of

The Journal of Integrated Healthcare Practitioners presents peer- reviewed articles on clinically relevant topics to healthcare providers. As advised by our Editorial Board, the separation of peer- reviewed material from news/stories/profiles delivers a message of strict academic rigor accompanying the compilation, review and publication of these clinically applicable scientific reviews.

1

2

58

63

2

Male Fertility

Role of oxidant stress and antioxidant therapy

3

Urinary Neurotransmitter Analysis Utility in depression management

by: Tara Campbell, ND Clinical Trial Coordinator, Canadian College of Naturopathic Medicine

71

p

Markers of Cardiovascular Risk

by: Elizabeth Cherevaty, ND Naturopathic Doctor, Norfolk Chiropractic Wellness Centre

p

1

Novel Cholesterol Subtypes by: Christopher Habib, ND and Philip Rouchotas, MSc, ND Clinic Director, Mahaya Forest Hill Integrative Clinic Editor-in-Chief, Integrated Healthcare Practitioner

p

3

53

p

Continuing Education: Intravenous Therapies Fish oil based lipid emulsions (FOBLE)

by: Heidi Fritz, MA, ND and Philip Rouchotas, MSc, ND Research Fellow, Canadian College of Naturopathic Medicine Editor-in-Chief, Integrated Healthcare Practitioner

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editor’s letter

Sauce Season!

A

s the leaves begin to turn, bushels of tomatoes are carefully transformed into litres upon litres of sauce... Winter is coming... Many would say “why bother? sauce costs about $3 per litre?” My reply; make 10 litres of sauce this fall... and you will remember with great joy each occasion you use them throughout the winter... The week or so before Christmas, through the first week or so of the new year, seem to me to be when the sauce is most appreciated. We managed to make 112 jars this year, down from the 153 a year ago, up from the 73 two years ago. We added a new item to the pantry this year; home made hot sauce! I look forward to experimenting with it through 2013... Thank you to Chris Haddad for the introduction to growing scotch bonnet peppers! We are privileged to introduce the first issue of the Journal of Integrated Healthcare Practitioners. Elizabeth Cherevaty, ND, has compiled an important body of literature reviewing the role of oxidant stress and antioxidant therapies in male fertility; Chris Habib, ND has compiled evidence highlighting the clinical significance of novel lipid markers of cardiovascular risk, adding to the scrutiny with which LDL remains the gold standard target of care for primary and secondary coronary prevention; Tara Campbell introduces urinary neurotransmitter testing, an approach allowing for objective quantification of individualized metabolic abnormality among patients with depression and other affective disorders; Heidi Fritz, MA, ND provides the continuing education lesson for the issue, focusing on intravenous application of fish oil- based lipid emulsions.

Best Regards, Philip Rouchotas, MSc, ND Editor-in-Chief We invite questions or comments. philip@ihpmagazine.com

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N AT U R A L M E D I C I N E

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12-10-03 12:42 PM


N AT U R A L M E D I C I N E

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peer review

Peer Review Board Members Aoife Earls, MSc, ND Trafalgar Ridge Chiropractic and Acupuncture 2387 Trafalgar Rd, Unit 7A Oakville, Ontario L6H 6K7 aearlsnd@gmail.com

Erin Balodis, BSc, MSc, ND Kingswood Chiropractic Health Centre 1210 Hammonds Plains Road Hammonds Plains, NS B4B 1B4 erinbalodis@gmail.com

Berchman Wong, ND 718 - 33 Canniff St Toronto, Ontario M6K 3M5 berchman.nd@gmail.com

Erin Psota, BSc, ND 626 King St West, Suite 201 Toronto, Ontario M5V 1M7 drpsota@gmail.com

Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 rozendaal@sympatico.ca

Faryal Luhar, ND Healthwise Wellness 4250 Weston Rd Toronto, Ontario M9L1W9 ndluhar@hotmail.com

Carol Morley, ND Zawada Health 201 City Centre Drive Suite 404 Mississauga, Ontario L5B 2G6 info@zawadahealth.comaa

Heidi Fritz, MA, ND Research Fellow Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 hfritz@ccnm.edu

Colin MacLeod, ND Alderney Chiropractic 164 Ochterloney St. Dartmouth, NS B2Y 1E1 info@drcolinmacleod.com

Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct # A Sebastopol, CA 95472-4528 ieliaz@sonic.net

Daniel Watters, BSc, ND Rosedale Wellness Centre 365 Bloor St East Toronto, Ontario M4W 3L4 wattersdaniel@hotmail.com

Jacob Scheer, DC, ND, MHSc 2100 Finch Ave. W. #206 North York, Ontario M3N 2Z9 Jacob.Scheer@utoronto.ca

David Miller, BSc, ND 60 Albert Street Southampton, Ontario NOH 2L0 davidjmillernd@gmail.com Elizabeth Cherevaty, BSc, ND Healing Foundations Naturopathic Clinic 111 Norfolk St., 2nd Floor Guelph, Ontario N1H 4J7 drliz@guelphnaturopathic.com

Jiselle Griffith, BSc, ND The Health Hub Integrated Clinic 35 Hayden St, Suite 109 Toronto, Ontario M4Y 3C3 info@jisellegriffith.ca Jordan Robertson, BSc, ND Lakeshore Clinic 2159 Lakeshore Road Burlington, Ontario L7R 1A5 jordanrobertsonnd@gmail.com

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peer review Judah Bunin, BSc, MSc, ND, DrAc Fredericton Naturopathic Clinic 10-150 Cliffe St Fredericton, NB E3A0A1 frednatclin@yahoo.ca

Sarah Vadeboncoeur, ND Ottawa Integrative Health Centre 1129 Carling Ave Ottawa, Ontario K1Y 4G6 sarahmvadeboncoeur@gmail.com

Karam Bains, BSc, ND Elixir Health Multiple Clinics karam@elixirhealth.ca

Scott Clack, ND Touchstone Naturopathic Centre 950 Southdown Rd, Unit B5 Mississauga, Ontario L5J 2Y4 sclack.nd@touchstonecentre.com

Kelly Brown, BSc, ND Healthview Therapy Centre 5118 Roblin Blvd Winnepeg, Manitoba R3R 0G9 drkbrownnd@gmail.com Leigh Arseneau, ND The Naturopathic Institute of Advanced Medicine 122 Simcoe St North Oshawa, Ontario L1G 4S4 docleigh@gmail.com Lindsay Bast, BSc, ND Greenwood Wellness Clinic PO Box 189 1400 Greenwood Hill Rd. Wellesley, ON N0B 2T0 Louise Wilson, BSc, ND 320 Queen St S Bolton, Ontario L7E 4Z9 Dr.louisewilsonnd@gmail.com Mandana Edalati, BA, ND Wellness Naturopathic Centre Suite 213-1940 Lonsdale Ave North Vancouver, British Columbia V7M 2K2 dredalati@gmail.com Melanie DesChatelets, BSc, ND True Health Studio 200-4255 Arbutus St Vancouver, British Columbia V6J 4R1 melanie@drdeschat.com Nicole Egenberger, BSc, ND Remede Naturopathics 214 Sullivan Street Suite 3B New York, New York 10012 info@remedenaturopathics.com Raza Shah, BSc, ND St. Jacobs Naturopathic 1-9 Parkside Drive St. Jacobs, Ontario N0B 2NO stjacobs.nd@gmail.com

Shawna Clark, ND Forces of Nature Naturopathic Clinic 2447 1/2 Yonge St Toronto, Ontario M4P 2E7 info@shawnaclarknd.com Stephanie Swinkles, DDS Elmsdale Dental Clinic 4-269 Highway 214 Elmsdale, Nova Scotia N2S 1K1 steph_moroze@hotmail.com Susan Coulter, BSc, ND Roots of Health 2-497 Laurier Ave Milton, ON L9T 3K8 scoulter@rootsofhealth.ca Sylvi Martin, BScN, ND Fusion Chiropractic and Integrative Health 735 Danforth Avenue Toronto, Ontario M4J 1L2 martin.sylvi@gmail.com Tanya Lee, BSc, ND The Health Centre of Milton 400 Main St East Suite 210 Milton, Ontario L9T 1P7 tanyalee.nd@gmail.com Terry Vanderheyden, ND Bayside Naturopathic Medicine 118 Bay Street Barryâ&#x20AC;&#x2122;s Bay, Ontario KOJ 1B0 doctrv@gmail.com Theresa Jahn, BSc, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, NS B3K 5B6 info@theresajahn.com

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editorial board

IHP Editorial Board Members The purpose of our Editorial Board is to help guide the direction of the publication, in a manner that A) improves academic quality and rigor, B) exerts a positive impact on patient outcomes, C) contributes to knowledge of integrative healthcare, and D) showcases evolving trends in the healthcare industry. We have appointed a dynamic mix of individuals representing integrative MD’s, profession-leading ND’s, and members of academia. This unique blend of minds comes together and has already provided

insight that is actively shaping the manner in which IHP is compiled. Our goal remains successful listing with the PubMed database of scientific literature, and the contributions of this incredible team are an important step in the right direction. IHP is grateful to the donation of time and expertise made by these incredible professionals. The best way we can think of honouring their contribution is to effectively implement their suggestions and thus continuously elevate the quality of delivery of this publication.

Ben Boucher, MD

Dr. Boucher is a Nova Scotian of Acadian-Metis heritage who spent his early years in Havre Boucher, NS. He attended St. Francis Xavier University where he graduated in 1973. In 1978, he obtained a Doctor of Medicine degree from Dalhousie University, NS. Since 1979, he has practiced rural medicine in Cape Breton, NS. Although he has a very large general practice, he has special interests in chelation therapy and metal toxicity. In the past three years, he has been recognizing and treating vector- transmitted infections. Dr. Ben does his best to help patients by following Sir William Osler’s approach whereby if one listens long enough to a patient, together the answer will be found.

Jason Boxtart, ND

Dr Boxtart is currently serving as Chair to the Board of Directors for the Canadian Association of Naturopathic Doctors, the national association of naturopathic medicine in Canada. In that position he also chairs the Canadian Naturopathic Coordinating Council, the national stakeholder group in Canada. He also is a Board member of the Canadian Naturopathic Foundation, the national naturopathic charity. For the last eight years Dr. Boxtart has held a Faculty of Medicine post with the University of Northern British Columbia. Jason, and his wife Dr. Cher Boomhower, ND, share the role of Medical Director for the Northern Center for Integrative Medicine, a multi-practitioner clinic in Prince George, BC.

Roger A. Brumback, MD

Dr Brumback completed his residency in paediatrics at John Hopkins Hospital as well as in child neurology at Washington University, St Louis Children’s Hospital. He also completed a fellowship in neurology and neuropathology at the National Institutes of Health. This was preceded by undergraduate and medical training at Pennsylvania State University. Roger has been a Professor of Pathology at the Creighton University School of Medicine in Omaha, Nebraska since 2001. In 1986 he founded the Journal of Child Neurology and has maintained his position as Editor-in-Chief to this day. He likewise accepted the appointment as Editorin-Chief of the Journal of Evidence- Based Complimentary and Alternative Medicine in 2011.

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editorial board

Pardeep Nijhawan, MD, FRCP(C), FACG

Dr. Nijhawan completed his medical school training at the University of Ottawa and proceeded to complete an internal medicine internship at Yale-Norwalk, CT. He completed his internal medicine residency and Gastroenterology and Hepatology fellowship at the Mayo Clinic in Rochester, MN. There he was awarded the Calgary fellowship for outstanding achievements. He is a member of the Royal College of Physicians and Surgeons of Canada, American Board of Gastroenterology, and American Board of Internal Medicine. In 2003, Dr. Nijhawan established the Digestive Health Clinic to help bring leading edge technology to Canada. He specializes in therapeutic endoscopy, irritable bowel and celiac disease.

Gurdev Parmar, ND, FABNO

Dr. Parmar is a respected leader in the field of Integrative Oncology. He and his wife, Dr. Karen Parmar, launched the Integrated Health Clinic in 2000 and have since facilitated its growth to become one of the largest and most successful integrated health care facilities in Canada. Dr. Parmar was the first Canadian naturopathic physician to hold a fellowship to the American Board of Naturopathic Oncology (FABNO), a board certification as a cancer specialist. Dr. Parmar has been a consulting physician at the Lions Gate Hospital chemotherapy clinic since 2008, creating the first Integrative Oncology service in any chemotherapy hospital in the country.

Kristy Prouse, MD, FRCSC

Dr. Prouse has practiced as an Obstetrician/Gynaecologist for over 10 years and currently holds the position of assistant professor at the University of Toronto and the Northern Ontario School of Medicine. Dr. Prouse completed her medical degree at Queen’s University and residency training at the University of Calgary. Additionally, Dr. Prouse has trained in bio-identical hormone replacement therapy and anti-aging and regenerative medicine through the University of Southern Florida-College of Medicine. She is the Founder and Chief Medical Officer at the Institute for Hormonal Health, an integrative medical practice in Oakville, Ontario that focuses on hormonal imbalances in both women and men. Kristy completed her residency training at the University of Calgary, while obtaining her medical degree from Queen’s.

Dugald Seely, ND, MSc

Dr Seely is a naturopathic doctor and director of research at the Canadian College of Naturopathic Medicine (CCNM). Dugald completed his masters of science in cancer research from the University of Toronto with a focus on interactions between chemotherapy and natural health products. In his current role as director of research, Dugald is the principal investigator for a number of clinical trials, and is actively pursuing relevant synthesis research in the production of systematic reviews and meta-analyses. Ongoing projects include three multicentred randomized clinical trials and a comprehensive CIHR synthesis review of natural health products used for cancer. Dugald is currently a member of Health Canada’s Expert Advisory Committee for the Vigilance of Health Products and is a peer reviewer for the Canadian Adverse Reaction Newsletter. 52 www.ihpmagazine.com l October 2012

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Novel Cholesterol Subtypes Markers of Cardiovascular Risk By Christopher Habib, ND Clinic Director Mahaya Forest Hill 102-73 Warren Road Toronto, ON M4V 2R9 info@chrishabibnd.com Philip Rouchotas MSc, ND Integrated Healthcare Practitioners Editor-in-Chief philip@ihpmagazine.com Bolton Naturopathic 64 King St W, Bolton, Ontario, L7E1C7

Implementation of aggressive treatment targets for LDL-C has been credited with materially reducing risk of all cause death, sudden coronary death, stroke, as well as reduced risk of non fatal major coronary events, principally among populations of patients in settings of secondary coronary prevention. None-theless, questions remain, notably the phenomena whereby many individuals suffering cardiovascular events do so while having very low levels of circulating LDL-C, the apparent failure of statin therapy to correct coronary artery calcification, and the controversy surrounding the role of statin therapy in settings of primary coronary prevention. A selection of novel lipid markers may be able to equip practitioners to better predict a patients cardiovascular risk; these markers may correct erroneous risk predictions based on LDL among a subset of patients for whom assessment of LDL-C has proven to be a poor predictor of risk, they may identify individuals at risk sooner than LDL assessment alone would detect risk, and they may show reduced risk among a subset of individuals with marginally elevated LDL-C, preventing over treatment. The following review will examine evidence surrounding the role of Lp-PLA2, Apo B, LDL-P, Lp(a), and LDL/ HDL subfractions in predicting risk of cardiovascular events. www.ihpmagazine.com l October 2012 53

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Introduction Guidelines for cholesterol testing to examine cardiovascular (CV) risk have primarily relied on measurements of lowdensity lipoprotein cholesterol (LDL-C) and secondarily on non-high-density lipoprotein cholesterol (HDL-C) (NCEP 2002). Patients are stratified by CV risk and then LDL-C treatment goals are set based on their classification. This LDL-C strategy has been successful in reducing the incidence of CV morbidity and mortality. Further analyses of clinical trial data have supported the idea that non-HDL-C is a better treatment target than LDL-C (Robinson 2009). Non-HDL-C includes both LDL-C and VLDL-C and it is derived from calculating total cholesterol minus HDL-C. However, measurements and treatment to non-HDL-C goals have not been utilized, largely as a result of knowledge gaps on behalf of physicians (Virani 2011). Even though statins and LDL-C reduction reduce CV events, there remains a residual risk for events in both primary and secondary prevention populations. Primary prevention

â&#x20AC;&#x153;Focusing treatment goals on LDL-C has been successful in reducing the incidence of CV morbidity and mortality.â&#x20AC;?

refers to avoiding the occurrence of disease. Secondary prevention refers to when disease is already present but before it causes significant morbidity. Residual risk is present in those who are on statin therapy and it is most evident in patients with metabolic syndrome and diabetes (Drexel 2010 & Rosenson 2010). As a result, the use of lipid biomarkers is a high-interest topic that has a large potential for clinical utility and to possibly improve patient outcomes. This is especially important as the availability of generic statins has decreased the cost of treatment and has improved the cost-effectiveness of using

lipid markers (Davidson 2011). This article will review the recent assessment of an expert panel of lipid specialists in their analysis of the following lipid markers: lipoproteinassociated phospholipase A2 (Lp-PLA2), apolipoprotein (Apo) B, LDL particle concentration (LDL-P), lipoprotein(a) [Lp(a)], and LDL and HDL subfractions (Davidson 2011). The evaluation of novel markers can provide valuable insight into a patientâ&#x20AC;&#x2122;s CV risk, especially where there is suspicion that a patient may be at higher risk than suggested by LDL-C alone. Current Guidelines Many epidemiological studies have confirmed that the following risk factors account for the majority of coronary artery disease (CAD) cases: age, male gender, cigarette smoking, diabetes mellitus, cholesterol (as assessed by total cholesterol and LDL-C), HDL-C, elevated blood pressure, a family history of premature CAD before the age of 60, inflammatory biomarkers such as hs-CRP, and overweight or obesity (Smith 2006). Other variables that increase risk are poor nutrition, caloric excess, physical inactivity, and psychological stress. Current cholesterol treatment targets are obtained from the data of clinical trials. Most studies measure the serum or plasma of LDL-C. The Cholesterol Treatment Trialists meta-analysis of 14 statin trials showed a dose-dependent relative reduction in cardiovascular disease (CVD) with LDL-C lowering (Baigent 2005). The CTT Collaborators found that every 1.0 mmol/L reduction in LDL-C is associated with a corresponding 20% to 25% reduction in CVD mortality and nonfatal myocardial infarction. Secondary targets include a total cholesterol to HDL-C ratio of less than 4.0, a non-HDL-C level of less than 3.5 mmol/L, an Apo B/Apo AI ratio of less than 0.80, a triglyceride level of less than 1.7 mmol/L and an hs-CRP level of less than 2.0 mg/L (Genest 2009). The current guidelines advocate optimizing these secondary targets in high-risk patients only after achieving LDL-C targets. Lp-PLA2 Lp-PLA2 circulates bound to LDL particles, HDL particles, Lp(a), and

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The Journal of IHP

triglyceride-rich remnant lipoproteins (Anderson 2008). It is produced by numerous cell types, including mast cells, macrophages, and liver cells (Braun 2010). LpPLA2 activity is up-regulated in atherosclerotic lesions and in rupture-prone fibrous caps (Koenig 2006). LpPLA2 is an enzyme responsible for the hydrolysis of oxidized phospholipids in LDL particles within the arterial intima and produces two highly inflammatory mediators (Anderson 2008). These mediators result in a cascade of events linked to atherosclerotic plaque formation, including the expression of cytokines and the production of foam cells (Braun 2010). Foam cells aggregate to form a fatty streak covered by a fibrous cap, while cytokines and proteases destroy the collagen within the fibrous cap, making it prone to rupture (Davidson 2011). Lp-PLA2 levels have been identified as a significant predictor of CV events and stroke (Braun 2010). In primary and secondary prevention trials, patients with Lp-PLA2 in the upper tertile or upper quartile had an approximately 2-fold increase in risk for CV events (Anderson 2008). In addition, unlike LDL-C, epidemiological studies show that an elevation in Lp-PLA2 confers a 2-fold increase in both first and recurrent strokes (Gorelick 2008). A meta-analysis of 80,000 patients showed that Lp-PLA2 elevations caused an 8% to 16% relative risk increases in the following: coronary heart disease (CHD), ischemic stroke, and vascular mortality (Lp-LPA2 Collaboration 2010). Interestingly, omega-3 fatty acids and weight loss have been shown to reduce Lp-LPA2 (Tzotzas 2008). Apo B All triglyceride-rich lipoprotein particles secreted by the intestine or the liver have one molecule of Apo B (Elovson 1988). The Apo B encircles the particle, provides external structural integrity, and stays with the lipoprotein particle for its lifetime. Thus, plasma Apo B concentration is a direct indication of the total number of circulating Apo B-containing lipoprotein particles. Atherosclerosis is initiated and advanced by the trapping of Apo B-containing lipoprotein particles within the subintimal space of the arterial wall (Davidson 2011). LDL Apo B particles have a greater importance in driving atherosclerosis because they are in greater concentration than VLDL Apo B particles and are smaller so they can enter the arterial wall more readily. The more Apo B particles enter the arterial wall, the greater the increase in the number trapped in the subendothelial space, and this leads to the development and progression of atherosclerosis (Smith 1982). LDL-C is not the best indicator of the risk attributable to LDL because risk correlates more closely with the number of circulating atherogenic particles than with

the quantity of cholesterol carried by those particles (Ingelsson 2007). The amount of cholesterol per LDL particle varies significantly. To better understand the problem this creates, consider a patient whose LDL particles contain less cholesterol than normal. This patient will have LDL-C concentrations that will underestimate the number of LDL particles. In such a patient, the Apo B concentration will more accurately reflect the number of LDL particles and the LDLrelated CV risk. Next, consider the reverse situation: a patient whose LDL particles contain more cholesterol than normal. In this patient, the LDL-C concentration will overestimate the number of LDL particles. In this case too, the Apo B concentration will provide a more accurate representation of LDL particles (Sniderman 2007). Cholesterol-poor LDL particles are the dominant form of LDL in a substantial portion of patients who are in all major clinical risk groups for vascular disease (Davidson 2011). In these groups, Apo B better reflects CV risk and this has been supported by a meta-analysis (Sniderman 2011). As a bonus, fasting is not required for Apo B measurement.

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LDL-P LDL particles can move into the arterial wall and the greater the circulating concentration of LDL particles, the greater the rate of passive diffusion into the arterial wall and the greater the vesicular ferrying through endothelial cells (Nielsen 1996). LDL particles bind to arterial wall proteoglycans, become oxidized, and are taken up by macrophages to form foam cells (Tabas 2007). When serum LDL-P is high, there are a greater amount of LDL particles in circulation and a greater amount of particles may enter the arterial wall. Conversely, when LDL-P is low, there are fewer LDL particles and a decrease in the initiation and promotion of atherosclerosis. LDL-P represents the number of LDL particles and is therefore an alternative way to quantify LDL, as oppose to relying solely only on LDL-C. For many patients, their LDL-C and LDL-P are highly correlated. However, because of variability of the cholesterol content and size of LDL particles, they are sometimes unrelated (Otvos 2002). In the general population, approximately 50% of subjects have discordance between LDL-C and LDL-P (Otvos 2011). In those with elevated triglycerides or low HDL-C, the discordance rates are higher and the same is true of those with type 2 diabetes mellitus or metabolic syndrome (Cromwell 2007, Otvos 2011). CV risk is more strongly associated with LDL-P than with LDL-C when these two measures are discordant (Otvos 2011). LDL-P and Apo B are both measures of particle number. As such, the decision to use one or the other is determined by availability, cost, and physician preference. www.ihpmagazine.com l October 2012 55

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Lp(a) Lp(a) is a modified LDL molecule with the addition of a protein made in the liver, known as the lipoprotein antigen (Koschinsky 2004). The lipoprotein antigen is highly polymorphic in size, which causes highly variable molecular weights and variable plasma concentrations in the population (Kronenberg 1999). Lp(a) is taken up in the arterial wall by scavenger receptors on macrophages called beta-integrin Mac-1 (Sotiriou 2006). Interestingly, homocysteine increases the Mac-1 interaction with Lp(a) antigen by up to threefold. Lp(a) also binds to fibrin and may enhance the clotting triggered by endothelial damage or plaque rupture (Koschinsky 2004). The number of molecules of Lp(a) appear to be the strongest determinant of related CV risk (Davidson 2011). When examining study data, Lp(a) has positive predictive power that is additive to other measures of lipoprotein risk factors (Davidson 2011). Lp(a) is specifically associated with increased risk for CHD in a continuous nonthreshold manner. The association between Lp(a) and CHD risk is independent of LDL-C, non-HDL-C, and the presence of other CV risk factors (Nordestgaard 2010). This makes Lp(a) a useful tool for assessing clinical risk, especially when there is a strong family history of vascular events, since elevated plasma concentrations are controlled by features of the Lp(a) gene (Kamstrup 2009). LDL and HDL subfractions Every lipoprotein particle in the LDL fraction is atherogenic, regardless of size. LDL particles become trapped in the arterial wall, cause foam cell formation, and cause the expansion of the inflammatory response (Ross 1999). HDL particles are involved in reverse cholesterol transport and also possess antiatherogenic properties, including antioxidant and anti-inflammatory properties (Rosenson 2011). Therefore, there is physiological rationale for the links between both LDL and HDL subfractions and adverse CV outcomes. LDL particles vary in size, density, and cholesterol content. Small LDL particles are often present in patients with features of metabolic syndrome, including those with CHD, diabetes, low HDL and high triglycerides, and in those with insulin resistance (Sacks 2003). However, the statistical associations between small, dense LDL and CHD outcomes are diminished or disappear altogether when adjusted for LDL-P. Currently, there are no patient subgroups that have been identified in which LDL subfractionation has supporting evidence showing benefit (Sacks 2003). HDL particles are also variable in terms of size, charge, density, and cholesterol content. Many antiatherosclerotic functions of HDL are not fully understood (Reilly 2007). Population studies support the notion that HDL-C has protective effects for CV risk and HDL subfractions also correlate with this risk (Williams

2011). Similar to LDL subfractions, there have been no patient subgroups in which there is evidence supporting the routine use of HDL subfractionation. Conclusion Focusing treatment goals on LDL-C has been successful in reducing the incidence of CV morbidity and mortality. However, LDL-C does not adequately assess risk in all population subgroups due to the variability of multiple associated factors. As a result, the use of lipid biomarkers has large potential for clinical applications and could improve patient outcomes. This article reviewed the recent assessment of the expert panel of lipid specialists in their analysis of multiple lipid markers. Lp-PLA2 elevations were shown to cause 8% to 16% relative risk increases in CHD, ischemic stroke, and vascular mortality. Apo B was shown to better reflect CV risk in a substantial portion of patients, especially in those patients with other major clinical risks for vascular disease. LDL-P was shown to be more strongly associated with CV risk than LDL-C, especially in patients with elevated triglycerides or low HDL-C, in those with type 2 diabetes mellitus, and in those with metabolic syndrome. Apo B and LDL-P are both measures of particle number and the merits of choosing one over the other or using both are unclear. Lp(a) was shown to be specifically associated with increased risk for CHD in a continuous nonthreshold manner, independently of many other risk assessment parameters. Finally, LDL and HDL subfractions were shown to be weaker predictors of CV risk, despite physiologic rationale that appeared promising for both. Overall, many of these lipid markers appear to be useful in certain patient subgroups. However, some controversies exist on their value and it is difficult to recommend when they should be used, or for which patients they would be most beneficial. Beyond that, it may also be difficult to determine how these markers may impact specific treatment goals or specific treatment decisions. ■

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Davidson MH, Ballantyne CM, Jacobson TA, Bittner VA, Braun LT, Brown AS, Brown WV, Cromwell WC, Goldberg RB, McKenney JM, Remaley AT, Sniderman AD, Toth PP, Tsimikas S, Ziajka PE, Maki KC, Dicklin MR.. Clinical utility of inflammatory markers and advanced lipoprotein testing: Advice from an expert panel of lipid specialists. J Clin Lipidol. 2011;5(5):338-367. Drexel H, Aczel S, Marte T, Vonbank A, Saely CH. Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis. Atherosclerosis. 2010;208(2):484-489. Elovson J, Chatterton JE, Bell GT, Schumaker VN, Reuben MA, Puppione DL, Reeve JR Jr, Young NL. Plasma very low density lipoproteins contain a single molecule of apolipoprotein B. J Lipid Res. 1988;29(11):1461-1473. Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GBJ, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Can J Cardiol. 2009;25(10):567-579. Gorelick PB. Lipoprotein-associated phospholipase A2 and risk of stroke. Am J Cardiol. 2008;101(12A):34F-40F. Ingelsson E, Schaefer EJ, Contois JH, McNamara JR, Sullivan L, Keyes MJ, Pencina MJ, Schoonmaker C, Wilson PW, D’Agostino RB, Vasan RS. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA. 2007;298(7):776785. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331-2339. Koenig W, Twardella D, Brenner H, Rothenbacher D. Lipoproteinassociated phospholipase A2 predicts future cardiovascular events in patients with coronary heart disease independently of traditional risk factors, markers for inflammation, renal function, and hemodynamic stress. Arterioscler Throm Vasc Biol. 2006;26(7):1586-1593. Koschinsky ML, Marcovina SM. Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity. Curr Opin Lipidol. 2004; 15(2):167-174. Kronenberg E, Kronenberg MF, Kiechl S, Trenkwalder E, Santer P, Oberhollenzer F, Egger G, Utermann G, Willeit J. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation. 1999;100(100):1154-1160. Lp-PLA(2) Studies Collaboration, Thomson A, Goa P, Orfei L, Watson S, Di Angelantonio E, Kaptoge S, Ballantyne C, Cannon CP, Criqui M, Crushman M, Hofman A, Packard C, Thompson SG, Collins R, Danesh J. Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375(9725):1536-1544. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106(25):3143-3421. Nielsen LB. Transfer of low density lipoprotein into the arterial wall and risk of atherosclerosis. Atherosclerosis. 1996;123(1-2):1-15. Nordestgaard BG, Chapman MJ, Ray K, Boren J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgozoglu L, Tybjaerg-Hansen A. European Atherosclerosis Society Consensus Panel. Lipoprotein (a) as a cardiovascular risk factor: current status. Eur Heart J. 2010; 31(23):2844-2853.

Otvos JD, Jeyarajah EJ, Cromwell WC. Measurement issues related to lipoprotein heterogeneity. Am J Cardiol. 2002; 90 (Suppl) (8A): 22i-29i Otvos JD, Mora S, Shalaurova I, Greenland P, Mackey RH, Goff DC Jr. Clinical implications of discordance between lowdensity lipoprotein cholesterol and particle number. J Clin Lipidol. 2011;5(2):105-113. Reilly MP, Tall AR. HDL proteomics: pot of gold or Pandora’s box? J Clin Invest. 2007;117(3):595-598. Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. 2009;53(4):316322. Rosenson RS, Davidson MH, Pourfarzib R. Underappreciated opportunities for low-density lipoprotein management in patients with cardiometabolic residual risk. Atherosclerosis. 2010;213(1):1-7. Rosenson RS, Brewer HB Jr., Chapman MJ, Fazio S, Hussain MM, Kontush A, Krauss RM, Otvos JD, Remaley AT, Schaefer EJ. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Cin Chem. 2011;57(3):392-410.

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Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med. 1999;340(2):115-126. Sacks FM, Campos H. Clinical review 163: Cardiovascular endocrinology 4: Low-density lipoprotein size and cardiovascular disease: a reappraisal. J Clin Endocrinol Metab. 2003;88(10):4525-4532. Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pasternak RC, Pearson T, Pfeffer MA, Taubert KA, AHA/ ACC, National Heart Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: Endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113(19):2363-72. Smith EB, Staples EM. Intimal and medial plasma protein concentrations and endothelial function. Atherosclerosis. 1982;41(23):295-308. Sniderman A, Tremblay A, Bergeron J, Gagne C, Couture P. Diagnosis of type III hyperlipoproteinemia from plasma total cholesterol, triglyceride, and apolipoprotein B. J Clin Lipidol. 2007;1:256-263. Sniderman AD, Williams K, Contois JH, Monroe HM, McQueen MJ, de Graaf J, Furberg CD. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337-345. Sotiriou SN, Orlova VV, Al-Fakhri N, Ihanus E, Economopoulou M, Isermann B, Bdeir K, Nawroth PP, Preissner KT, Gahmberg CG, Koschinsky ML, Chavakis T. Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J. 2006;20(3):559-561. Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007;116(16):1832-1844. Tzotzas T, Filippatos TD, Triantos A, Bruckert E, Tselepis AD, Kiortsis DN. Effects of a low-calorie diet associated with weight loss on lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in healthy obese women. Nutr Metab Cardiovasc Dis. 2008;18(7):477-482. Virani SS, Woodard LD, Landrum CR, Pietz K, Wang D, Ballantyne CM, Peterson LA. Institutional, provider, and patient correlates of low-density lipoprotein and non-high-density lipoprotein cholesterol goal attainment according to the Adult Treatment Panel III guidelines. Am Heart J. 2011;161(6):1140-1146. Williams PT, Feldman DE. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman’s Livermore Cohort. Atherosclerosis. 2011;214(1):196-202.

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Male Fertility

Role of oxidant stress and antioxidant therapy By Elizabeth Cherevaty ND Norfolk Chiropractic Wellness Centre 86 Norfolk St., Suite 101 Guelph, ON N1H 4J2 www.guelphnaturopathic.ca

Infertility is a significant problem affecting 15% of couples worldwide. Forty percent (40%) of infertility cases are attributable to male factors. Chronic and excessive levels of oxidative stress are increasingly recognized to contribute to chronic disease development, and a growing body of evidence points to a significant role of oxidative stress in the pathogenesis of infertility in men. This article outlines the pathogenic role of oxidative stress in male infertility and provides an overview of the evidence supporting the therapeutic use of selected dietary antioxidants (L-carnitine and L-acetylcarnitine, selenium, N-acetyl-cysteine, folate, zinc and vitamin C) in the integrative care of men with this condition.

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Male Factor Infertility Male factor infertility accounts for 40% of all cases of infertility (Akmal 2006, Tremellen 2008). The most common form of male infertility is oligoasthenoteratospermia (OAT) (Cavallini 2006, Ross 2010). There is no accepted medical treatment for OAT, while mechanical techniques such as IVF-ICSI (in vitro fertilization/intra-cytoplasmic sperm injection) are used to circumvent it (Cavallini 2006, Ross 2010, Safarinejad 2009). However, these procedures fail to address the potentially reversible, underlying causes of OAT (Ross 2010) and are not without significant physical, emotional and financial consequences for couples. While thirty percent (30%) of OAT cases are diagnosed as idiopathic (Cavallini 2006, Ross 2010), several factors including subtle endocrine abnormalities, environmental toxins, chronic inflammation or infection, obesity, sperm autoimmunity, genetic or constitutional factors, and excessive levels of oxidative stress induced by reactive oxygen species (ROS), have been implicated in the pathogenesis of OAT (Cavallini 2006, Comhaire 2000, Ross 2010, Safarinejad 2009). Many of the aforementioned factors can independently increase oxidative stress, while additional oxidation resulting from psychological stress, chronic diseases such as diabetes, smoking, alcohol, certain drugs, low fruit and vegetable intake may further contribute to OAT (Tremellen 2008). In fact, up to 30% to 80% of cases of male infertility have been linked to oxidative stress (Tremellen 2008 citing McLachlan 2001). Oxidative Stress and Male Infertility Seminal plasma contains the highest concentration of antioxidants of any human fluid (Cavallini 2006). In fact, sperm and seminal plasma are natural repositories for enzymatic and non-enzymatic antioxidants, including superoxide dismutase, glutathione peroxidase, catalase, vitamins C and E, glutathione and carnitine (Ross 2010), which are capable of protecting sperm from ROS-induced damage (Cavallini 2006). The principal generators of ROS in seminal fluid are sperm cytoplasm and leukocytes (Ross 2010). Spermatozoa produce ROS as part of normal metabolic processes, and are particularly vulnerable to oxidative stress due to their high cell membrane polyunsaturated

fatty acid content, limited capacity for DNA repair, and the removal of most of their antioxidant-containing cytoplasm during sperm maturation (Ebisch 2007, Menezo 2007). Despite the normally high seminal antioxidant content, excessive generation and/or decreased scavenging of ROS may lead to accumulation of ROS with consequent oxidative damage to sperm DNA, cell membranes and proteins, leading to apoptosis (and thereby oligospermia), atypical morphology (teratospermia) and impaired motility (asthenospermia) (Ebisch 2007, Ross 2010). Oxidative cell membrane damage also impairs spermoocyte fusogenic capacity (Tremellen 2008). Oxidative DNA damage, including that induced through certain assisted reproductive technologies, can compromise the paternal genomic contribution to the embryo and could result in decreased pregnancy rates, increased miscarriage risk and unknown genetic consequences in offspring (Comhaire 2003, Menezo 2007, Tremellen 2008).

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ANTIOXIDANT THERAPY IN INFERTILITY: SELECTED AGENTS Carnitine In a review of prospective clinical trials, Cavallini et al. (2006) found L-carnitine (LC) and L-acetyl-carnitine (LAC) to be significantly more effective than placebo at improving fertility in men with idiopathic OAT. Zhou et al. (2007) systematically reviewed nine randomized controlled trials involving a total of 862 infertile men aged 18-65 years, the majority diagnosed with OAT, who had taken either LC, LAC, both carnitines together, or carnitines with other agents (NSAIDs, vitamin E or vitamin C) at dosages of 2-3 g daily in single or divided doses for 24 weeks to six months (Zhou 2007). Metaanalysis of seven eligible trials identified a markedly significant increase in pregnancy rates with carnitines, reporting 55 pregnancies in the treatment group and nine in the control group (odds ratio=4.10, 95% CI: (2.08, 8.08)), (p<0.0001). Compared to placebo or other agents, carnitines also significantly increased total sperm motility (p=0.01) and forward motility (p=0.04) and decreased atypical morphology (p<0.00001), but did not significantly influence sperm concentration. www.ihpmagazine.com l October 2012 59

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LC is concentrated by active transport from the systemic circulation into the epididymal lumen (Ahmed 2011) where it accumulates as both LC and LAC (Zhou 2007). During sperm maturation in the epididymis, spermatozoa themselves accumulate LC (Ahmed 2011). LC acts as an antioxidant in seminal fluid, protecting sperm membranes and DNA from various mechanisms of oxidative stress (Zhou 2007). LC is essential to mitochondrial beta-oxidation of long chain free fatty acids (Zhou 2007, Moradi 2010), removes excess intracellular toxic acetyl-CoA (Zhou 2007) and is believed to serve as a post-ejaculatory energy source for sperm (Ahmed 2011). Ahmed et al. (2011) found seminal LC levels to be significantly lower in infertile men than

“Seminal plasma contains the highest concentration of antioxidants of any human fluid”

fertile men, while higher seminal carnitine levels have been positively associated with improved sperm count, motility and normal morphology. Comparing the effects on sperm parameters of LC (2 g/day) to those of the anti estrogen, clomiphene citrate (25 mg/ day), Moradi et al. (2010) found LC to be superior to clomiphene at increasing semen volume and equally effective at increasing sperm count and motility after three months of therapy; LC induced no significant effect on sperm morphology (Moradi 2010). Selenium and N-acetyl-cysteine Essential to normal spermatogenesis,

sperm motility and function, selenium (Se) is considered to improve semen quality and male fertility through the action of glutathione peroxidases (GPXs), Secontaining antioxidant enzymes in seminal fluid that decrease propagation of ROS by reducing H2O2 and lipid peroxides to alcohols and water (Cavallini 2006, Mistry 2012, Safarinejad 2009). The intracellular antioxidant glutathione (GSH) is a cofactor for GPX and reacts directly with ROS and cytotoxic aldehydes to protect sperm from the effects of lipid peroxidation (Atig 2012). N-acetyl-cysteine (NAC) is a derivative of L-cysteine and a precursor to GSH that also possesses direct free radical scavenging activity (Safarinejad 2009). An open prospective study involving 27 infertile men showed that 600 mg NAC plus fatty acid supplementation (1 g docosahexaenoic acid, 0.25 g gamma-linolenic acid and 0.10 g arachidonic acid) daily significantly reduced seminal ROS and increased sperm count in oligospermic men (Comhaire 2000). A recent prospective controlled study involving 250 infertile men identified significant positive correlations between seminal selenium and selenoenzyme concentrations and sperm motility (Atig 2012). Investigating the effects of Se, NAC, or the two antioxidants in combination, Safarinejad and Safarinejad (2009) conducted a doubleblind, placebo controlled, randomized trial in a cohort of 468 infertile men with idiopathic OAT. Participants received either 200 µg Se (n=116), 600 mg NAC (n=118), 200 µg Se plus 600 mg NAC (n=116), or placebo (n=118) daily for 26 weeks. None of the participants had Se deficiency or low blood plasma NAC at the outset of the study. Compared to placebo, all three treatment groups showed significant improvements from baseline in sperm concentration, mean total sperm count (30% increase), motility (19% increase), and normal morphology (26% increase). Se and/or NAC also produced significant

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decreases in serum LH and FSH and increases in serum testosterone and inhibin B, a marker of Sertoli cell function (Cavallini 2006). Seminal plasma Se and NAC were significantly and positively correlated to sperm count, concentration, motility and percent normal morphology, with the sum effects of seminal Se and NAC showing stronger correlations with increased sperm concentration (r=0.67, p=0.01), motility (r=0.64, p=0.01) and percent normal morphology (r=0.66, p=0.01). No adverse events were reported with Se or NAC intake (Safarinejad 2009). Folate and Zinc Zinc (Zn) is concentrated in the prostate gland, seminal plasma and spermatozoa (Atig 2012, Ebisch 2007). It is a cofactor for more than 80 metalloenzymes involved in DNA transcription, translation and repair, underscoring its importance in sperm cell development (Atig 2012, Colagar 2009, Ebisch 2007). Zn has important antioxidant and anti-apoptotic properties and supports the function of steroid hormone receptors (Atig 2012, Ebisch 2007). Depleted seminal plasma Zn levels have been correlated with idiopathic subfertility and lower sperm counts in several studies (Ebisch 2007). Significant and positive correlations have been reported between seminal Zn levels and sperm count (r=0.32, p<0.01) and normal morphology (r=0.42, p<0.001), with significantly higher seminal Zn levels noted among fertile men than infertile men (Colagar 2009). A recent prospective trial of 250 infertile men found seminal Zn concentrations to be significantly and positively correlated with sperm motility and concentration (Atig 2012). Based on National Health and Nutrition Examination Survey (NHANES, 19992000) (U.S.) data, 79% of men are estimated to consume less than the recommended dietary allowance (RDA) of Zn in their diets (Young 2008). Zn is also a cofactor for the folate-metabolizing enzymes dihydrofolate reductase and gamma-glutamyl hydrolase, as well as for methionine synthetase and betaine-homocysteine methyltransferase, which indirectly support the folate cycle through methionine metabolism (Ebisch 2007). Both folate and zinc possess anti-apoptotic properties, although excessively high zinc levels can induce apoptosis and necrosis (Ebisch 2007). Zinc deficiency decreases the intestinal absorption and

metabolism of folate (Ebisch 2007, Forges 2007). Folate is essential to healthy reproduction due to its role in nucleic acid synthesis and thereby the proliferation of rapidly dividing cells including sperm cell precursors (Ebisch 2007, Forges 2007). Folic acid, the synthetic form of folate, scavenges free radicals and prevents lipid peroxidation in sperm cell membranes and protects DNA from oxidative damage (Ebisch 2007). Various folates are concentrated in seminal plasma and the concentration of non-methyltetrahydrofolate has been significantly positively correlated with sperm count and concentration (Forges 2007). Folate may have a beneficial effect on spermatogenesis through improving cohesion of seminiferous epithelial cells and thereby preventing premature release of immature sperm into the tubules (Forges 2007). Folate deficiencyinduced hypomethylation of DNA and phospholipids may impair testicular exocrine and endocrine functions (Forges 2007). Folate deficiency also precipitates hyperhomocysteinemia, a pro-inflammatory state that is linked with poor sperm quality and male infertility (Forges 2007). Used in combination with other antioxidants, folic acid has improved sperm concentration and pregnancy rates in studies involving assisted contraception (Ross 2010 citing Tremellen 2007 and Wong 2002). NHANES data estimate that 64% of men consume less than the RDA of dietary folate (Young 2008). Dividing 94 subfertile (sperm concentration 5 x 106/ ml to 20 x 106/ml) and 99 fertile men into four treatment groups, folic acid (5 mg/day) and zinc sulfate (66 mg/ day) together, folic acid or zinc plus a placebo, or two placebos, were administered to participants for six months (Forges 2007 citing Wong 2002). Folic acid and zinc together produced a substantial 74% increase in sperm concentration and count in subfertile men compared to fertile controls, although none of the men had zinc or folate deficiency prior to treatment (Forges 2007 and Comhaire 2000 citing Wong 2002). No significant changes were observed with separate administration of folate or zinc (Forges 2007 citing Wong 2002).

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Vitamin C Higher dietary and supplemental intake of vitamin C has been correlated with higher sperm count, concentration and progressive motility (Eskenazi 2005). www.ihpmagazine.com l October 2012 61

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In a small open study involving 13 infertile men 25 to 35 years of age, 1000 mg vitamin C taken twice daily for two months produced significant increases in mean sperm count from 14.3 x 106 to 32.8 x 106 sperm/mL (p<0.001), normal morphology from 43% to 66.7% (p<0.001), and sperm motility from 31.2% to 60.1% (p<0.001) (Akmal 2006). A group of 36 infertile men with asthenoteratozoospermia and leukocytospermia showed significant improvements in progressive motility and morphology with decreased necrosis and leukocytosis after treatment with 60 mg vitamin C, 10 mg vitamin E, 100 mg fermented papaya, 194 mg lactoferrin and 40 mg beta-glucan daily for three months (Piomboni 2008). Ménézo (2007) administered a combination of 400 mg vitamin C with 400 mg vitamin E, 18 mg beta-carotene, 500 µmol Zn and 1 µmol Se daily for 90 days to 58 men with sperm DNA abnormalities and a history of at least two IVF or ICSI failures. Treatment

significantly decreased sperm DNA fragmentation, but paradoxically increased sperm head decondensation, a phenomemon that when exceeding a critical threshold of 28% is associated with greater risk of chromosome condensation abnormalities and poorer prognosis for pregnancy with IVF or ICSI (Ménézo 2007).

References

Mistry HD, Broughton Pipkin F, Redman CW, Poston L. Selenium in reproductive health. Am J Obstet Gynecol. 2012 Jan;206(1):21-30.

Ahmed SD, Karira KA, Jagdesh, Ahsan S. Role of L-carnitine in male infertility. J Pak Med Assoc. 2011 Aug;61(8):732-6. Akmal M, Qadri JQ, Al-Waili NS, Thangal S, Haq A, Saloom KY. Improvement in human semen quality after oral supplementation of vitamin C. J Med Food. 2006 Fall;9(3):440-2. Atig F, Raffa M, Habib BA, Kerkeni A, Saad A, Ajina M. Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. BMC Urol. 2012 Mar 19;12:6. Cavallini G. Male idiopathic oligoasthenoteratozoospermia. Asian J Androl 2006; 8(2):143-157. Colagar AH, Marzony ET, Chaichi MJ. Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr Res 2009;29:82-88. Comhaire FH, Christophe AB, Zalata AA, Dhooge WS, Mahmoud AM, Depuydt CE. The effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertile men. Prostaglandins Leukot Essent Fatty Acids. 2000 Sep;63(3):159-65. Comhaire FH, Mahmoud A. The role of food supplements in the treatment of the infertile man. RBM Online 2003;7(4):385-391. Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007 MarApr;13(2):163-74. Eskenazi B, Kidd SA, Marks AR, Sloter E, Block G, Wyrobek AJ. Antioxidant intake is associated with semen quality in healthy men. Hum Reprod. 2005 Apr;20(4):1006-12. Forges T, Monnier-Barbarino P, Alberto JM, Guéant-Rodriguez RM, Daval JL, Guéant JL. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update. 2007 May-Jun;13(3):225-38. Ménézo Y. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. RBM Online 2007:14(4):418-421.

Conclusion The majority of literature reviewed consists of relatively small but positive studies showing benefits to sperm quality and in some cases pregnancy rates with treatment of infertile men with various single or combination antioxidants, with few adverse effects. Recognizing the role of oxidative stress in the pathogenesis of numerous serious chronic diseases, reducing the oxidative burden in affected men is likely to benefit sperm quality and fertility as well as their overall health in the longer term. ■

Moradi M, Moradi A, Alemi M, Ahmadnia H, Abdi H, Ahmadi A, Bazargan-Hejazi S. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study. Urol J. 2010 Summer;7(3):188-93. Piomboni P, Gambera L, Serafini F, Campanella G, Morgante G, De Leo V. Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia. Asian J Androl. 2008 Mar;10(2):201-6 Ross C, Morriss A, Khairy M, Khalaf Y, Braude P, Coomarasamy A, El-Toukhy T. A systematic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online. 2010 Jun;20(6):711-23. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetylcysteine for improving semen parameters in infertile men: a doubleblind, placebo controlled, randomized study. J Urol 2009;181:741-751. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update 2008;14(3):243-258. Tremellen K, Miari G, Froiland D, Thompson J. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Aust N Z J Obstet Gynaecol. 2007 Jun;47(3):216-21. (Cited in Ross 2010). Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002 Mar;77(3):491-8. Young SS, Eskenazi B, Marchetti FM, Block G, Wyrobek AJ. The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod. 2008 May;23(5):1014-22. Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetylcarnitine in nutrition treatment for male infertility: a systematic review. Asia Pac J Clin Nutr 2007;16(Suppl 1):383-390.

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Urinary Neurotransmitter Analysis Utility in depression management 3

By Tara Campbell, ND Continuum Wellness 301-3402 Yonge St Toronto, Ontario, M4N2M9 ndtara@gmail.com Canadian College of Naturopathic Medicine Clinical Trial Coordinator

Given the pervasiveness of anxiety and depression in todayâ&#x20AC;&#x2122;s society and the limitations of the current standard of care for many patients, there is a need for reliable neurobiological assessments that objectively identify underlying biochemical abnormalities as plausible therapeutic targets. Measurement of neurotransmitters is an excellent candidate to serve as an objective framework of diagnosis, prognosis, and response to treatment in psychiatry; neurotransmitters can be measured in various biological fluids including blood serum, platelets, cerebral spinal fluid (CSF), saliva, and urine. Currently biomarkers for depression and anxiety are not utilized in standard medical practice, and tools upon which to base treatment decisions are restricted to the evaluation of subjective clinical symptoms. Without information yielded from objective testing, selection of the best treatment for each person with a mood disorder remains challenging, and is often determined through a time-consuming process of trial and error. Urinary neurotransmitter testing is rapidly becoming the preferred bodily fluid for objective neurobiological assessment since a) urine is the primary route of neurotransmitter elimination, and b) it is a non-invasive and cost effective testing method.

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Introduction The nervous system is the central control mechanism for nearly every bodily process. Within the nervous system neurotransmitters serve as chemical messengers for trillions of connections between the brain and target tissues, and they are essential for maintaining body homeostasis (Marc 2011). In response to prolonged stress however, the biological system begins to lose its ability to maintain chemical homeostasis; as a result, disease processes may be initiated (Lurie 1991). Imbalances in neurotransmission, due to excessive or deficient levels of certain neurotransmitters, are associated with depression, anxiety, insomnia, behavioral disorders, memory disorders, and a spectrum of other neurological disorders (Marc 2011). Since neurotransmitters are thought to play an integral role in mediating these disease processes, the measurement of specific imbalances may be of use in guiding targeted interventions that are aimed at correcting the individual excess or deficiency in question. The importance of effectively assessing and treating depression cannot be overstated. The World Health Organization’s Global Burden of Disease Study places unipolar affective disorder among the 10 leading medical causes of disability in the world, second only to ischaemic heart disease (Murray 1997). The current standard of care for depression is to embark upon a course of treatment, most likely a pharmaceutical intervention, based on its efficacy in randomized clinical trials, its specificity or “match” for the patient’s symptomatology, or the patient’s previous response(s) to treatment (Fava 2005). The patient is then monitored for a good outcome, allowing for course correction if there is no improvement. Both steps fundamentally rely on clinical findings and subjective data. Clearly, objective data would further enhance the medical assessment, if available (Holsboer 2008). Clinical Utility of Biomarkers As in any other disease state, a primary goal in the research of mental health disorders is the identification of specific biomarkers that could enhance the ability to develop targeted patient treatments in order to enhance patient management and to improve treatment success (Holsboer 2008). Biomarkers are commonplace in most branches of medicine. For example, if a patient has cancer, heart failure or even a bladder infection, a medical practitioner will likely intervene with the appropriate laboratory testing before committing to any course of treatment. Tumor markers are used in oncology (Srinivas 2001), troponin is a biomarker

in cardiology (Sato 2012), C-reactive protein (CRP) and Rheumatoid Factor (RF) are biomarkers in rheumatology (Dasgupta 2012), and prostatespecific antigen (PSA) is used in the detection and management of prostate cancer (Chang 2012). In the context of these conditions, biomarkers are important for diagnosis, early detection, patient monitoring, prognosis, prediction of safety and appropriate dosing. With so many biomarkers available for other medical conditions, why is there no formalized biomarker in psychiatry? In the past, biomarkers for brain health assessments have been viewed as irrelevant to symptomatology because measures had included peripheral biological fluids (blood, urine, and saliva) as opposed to central nervous system markers, such as cerebrospinal fluid and brain tissue, which are far too costly and invasive to use in clinical practice (Roy 1988). A common misconception about peripheral biochemistry is that it cannot serve as a biological indicator of central nervous system (CNS) activity due to the presence of the blood-brain-barrier, which limits the transport of neurotransmitters from the peripheral nervous system (PNS) to the CNS and vice versa. The CNS and PNS must not be viewed as separate entities, however. In reality, central neurotransmitters are carried to the periphery via specific blood brain barrier (BBB) transporters followed by renal filtration with subsequent excretion of neurotransmitters in the urine (Lechin 2006). A study by Lechin demonstrated that specific CNS nuclei can manipulate peripheral neurochemistry, and peripheral neurochemistry can affect central pathways (e.g. vagal afferents from periphery to CNS) (2006). The CNS and PNS also communicate via direct neuronal projections (Moreira 2011). Finally, animal studies have suggested a relationship between urinary and CNS neurotransmitters (Lynn-Bullock 2004). The kidneys also have neurotransmitter transport mechanisms. Circulating neurotransmitters are filtered from the blood by nephrons and subsequently excreted in the urine through glomerular filtration and by active transport via organic cation transporters (OCT’s) (Moleman 1992). Two mechanisms of neurotransmitter transport in the kidneys have been well established: (1) monoamine neurotransmitters are excreted by ultrafiltration from arterial blood into the glomeruli, secreted in the proximal tubules, subsequently distributed through the collecting duct to the urinary bladder and excreted in the urine (Graefe 1997); (2) in the luminal and basolateral membranes of the renal proximal tubules, OCT2 is responsible for the reabsorption and secretion

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of endogenous compounds, including monoamine neurotransmitters (Koepsell 1998). According to Cook, certain criteria must be met for a biomarker to be considered for psychiatric management (2008). First, the biomarker must be timely, clinically useful, and cost-effective. Second, the technology needed to assess the biomarker must be well tolerated by the target patient population. Third, methods that can be easily integrated into the practitionerâ&#x20AC;&#x2122;s current practice patterns are more likely to be accepted than those that require a major change in the delivery of care. Urine testing of neurotransmitters satisfies all three of these criteria. Value of Urinary Neurotransmitter Testing Many people, patients and practitioners alike, are familiar with the role of serotonin in depression (Genung 2012), and most antidepressant medications target the extracellular availability of serotonin and/or norepinephrine (Rozas 2009). Practitioners are less likely to investigate or address other important neurotransmitters/ neuromodulators involved in brain processes such as GABA, glycine, asparagine, glutamate, taurine, dopamine, epinephrine, norepinephrine, cortisol, phenylalanine, tyrosine, melatonin and histamine (Duncan 2012, Fu 2012, Hovelso 2012, Tamatam, 2012) (See Figures 1,2, and 3). The considerable variability in neurotransmitters/ neuromodulators may provide a possible explanation for why so many people using anti-depressant medications or supplements sometimes find little-to-no relief from their treatment (Eby 2010, Fournier 2010, Rozas 2009); in fact, sixty percent of cases of clinical depression are considered to be treatment-resistant (Eby 2010). The assessment of urinary neurotransmitter testing offers the possibility of improving treatment outcomes in these cases by allowing correction of the underlying imbalance. In addition,

pharmacological based antidepressant intervention can take weeks or months to tweak and perfect, if indeed this can be achieved at all (Hamer 2011, Oyebode 2012, Waterreus 2012), and the use of biomarkers to select the most appropriate intervention and monitor treatment response may possibly expedite this process. Indeed, a current trend in psychiatry includes the selection of anti-depressants that address several targets at once, due to the modest to negligible efficacy of highly selective drugs (Razas 2009); and this trend speaks to the difficulty of correctly selecting highly selective agents based on symptomatology alone. Studies show depression to be a long term, relapsing condition associated with significant tendency towards chronicity. Three quarters of patients with depression experience more than one episode of depression and the risk of recurrence is higher if the first episode occurs at a younger age and if there is a family history of depression (Hollon 2006). The risk of recurrence increases with each new episode and as the number of depressive episodes increases, the influence of life stress on recurrence wanes (Kendler 2000). Given these findings, the need for effective treatment in the first episode of depression is obvious (Palazidou 2012). Targeted testing can help to determine exactly which neurotransmitter levels are out of balance, and in turn, which therapies are best suited for an individualized treatment plan (Holsboer 2008). There exists a welldeveloped body of literature correlating urinary levels of various neurotransmitter metabolites to mood disorders, the focus of the following review being depression. With objective evidence of the specific neurotransmitter imbalances of a particular patient, a clinician is much better equipped to individualize a treatment plan targeting the imbalances unique to each presenting case.

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Neurotransmitter Assessment in Depression Figure 1: Catecholamine Pathway

Figure 2: GABA Pathway

adapted from https://www.neurorelief.com/content/engine/spaw/uploads/files/Catecholamine_pathway.pdf

adapted from https://www.neurorelief.com/content/engine/spaw/uploads/files/GlutamateGABA_pathway.pdf

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Figure 3: Serotonin Pathway

adapted from https://www.neurorelief.com/content/engine/spaw/uploads/files/Serotonin_Pathway.pdf

Neurotransmitter Assessment in Depression Thirty-six depressed patients seen at the National Institute of Mental Health were assessed for urinary and cerebrospinal fluid (CSF) measures of dopamine and dopamine metabolites. Episodes of suicidality among the patients were documented five years later. Baseline CSF and urinary assessment of dopamine (and metabolites) was then compared. The team showed urinary measures of dopamine and metabolites to be a much more powerful predictor of suicide attempt than CSF measures (Roy 1994). Seventy-five female patients with purging bulimia nervosa (BN) and 30 healthy controls were compared for psychopathology (impulsivity, borderline personality traits, depressive symptoms and self-defeating personality traits) and neurobiological parameters reflecting hypothalamicpituitary-adrenal axis activity (morning serum cortisol before and after dexamethasone) and monoamine activity (24-hour urinary excretion of norepinephrine, serotonin, dopamine, and their main metabolites: 3-methoxy-4hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid). BN patients had lower 24-hour excretion of serotonin and dopamine than controls, as well as lower ability to suppress cortisol (Val-Leal 2011). Roy and colleagues examined subsets of unipolar depressed patients and compared these subjects to non-depressed controls. They found that depressed patients had high urinary norepinephrine and its metabolite normetanephrine, but lower urinary output of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) compared to controls. They concluded that high urinary output of norepinephrine and normetanephrine reflected abnormal sympathetic nervous system activity and suggested that urinary neurotransmitter testing may be

helpful in determining subsets of depression (Roy 1986). Other studies also confirmed these findings, which reported elevations in urinary norepinephrine output in depressed and anxious individuals (Grossman 1999, Koslow 1983, Roy 1988). Otte and colleagues likewise demonstrated elevated urinary excretion of norepinephrine in depressed patients, yet found no difference in levels of urinary dopamine and metabolites relative to healthy controls (Otte 2005). Hughes (2004) observed that higher levels of depressive symptoms, as assessed by the Beck Depression Inventory (BDI), were associated with increased norepinephrine and cortisol excretion in the urine. In this study, ninety one women aged 47-55 years were evaluated and 24-hour urine collections were assayed for epinephrine, norepinephrine and cortisol. Depressed women (n=17, BDI scores >/=10) exhibited a 25% higher rate of urinary norepinephrine excretion than women with BDI scores <10 (n=74), P=.007. Higher levels of state anxiety were also related to greater NE excretion; likewise, cortisol excretion was related to both depression and anxiety. Interestingly, depression and anxiety symptoms were unrelated to urinary epinephrine excretion. Of tremendous significance to a discussion of the clinical utility of assessment of urinary neurotransmitter levels is the response of these levels to various types of treatment; do abnormal levels of urinary neurotransmitters correct themselves following various treatments for depression, natural or prescription? Do treatment responders differ in the impact of treatment to urinary levels of neurotransmitters from treatment non responders? Nichkova et al (2012) evaluated the clinical utility of a novel ELISA for the measurement of serotonin in urine from depressed subjects and from subjects under antidepressant therapy. Results demonstrated significantly

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The Journal of IHP

lower serotonin levels in depressed patients (87.53±4.89 μg/g Cr; n=60) than in non-depressed subjects (153.38±7.99 μg/g Cr). This study also demonstrated that urinary excretion of serotonin in depressed individuals significantly increased after antidepressant treatment by the dietary supplement 5-HTP and/or selective serotonin re-uptake inhibitor. Similarly, a double-blind, placebocontrolled, block-randomized, two-way crossover study designed to assess vascular safety administered 20 mg/d of the SSRI paroxetine. Urinary serotonin excretion increased significantly (89%) when compared to placebo 24-hours after oral administration (Kotzailias 2004). Thirty-six un-medicated depressed patients were assigned to one of four groups; placebo, fluoxetine, duloxetine, or St John’s Wort. At baseline and following eight weeks of treatment, patients were assessed for urinary levels of melatonin. As anticipated, all three antidepressant treatments significantly increased urinary melatonin levels, while placebo had no effect (Carvalho 2009). Thirty- five subjects aged 55-75 were assigned to receive tryptophan- fortified cereal (60mg per 30g cereal) and followed for a three- week period. Tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency. Urinary 6-sulfatoxymelatonin (melatonin metabolite), and 5-hydroxyindoleacetic acid (serotonin metabolite) levels increased respectively. Anxiety and depression symptoms were also improved (Bravo 2012). A novel tart-cherry product has similarly been shown to reduce urinary levels of cortisol and increase urinary levels of 5-hydroxyindoleacetic acid, suggesting a role for the cherry in stress control/ mood regulation (Garrido 2012). Of note is an investigation by Linnoila and colleagues (1984). After a series of studies evaluating urinary catecholamine levels in depressed patients, and their response to treatment, the team followed a small subset of depressed patients (21) regarding urinary serotonin and 5-hydroxyindoleacetic acid (5-HIAA). Three of the patients suffered from rapid cycling bipolar disorder (RCBD), a rare and difficult to treat variant of bipolar. The patients with RCBD demonstrated quite dramatically elevated levels of urinary serotonin and 5-HIAA, that were corrected upon administration of lithium. This small sample of patients suggests low levels of urinary serotonin correlate to depression, while elevated levels of urinary serotonin may correlate to mania and mood cycling.

Conclusions Overall, urinary neurotransmitter analysis can be a useful tool in clinical assessment and treatment for depression as well as other mood based disorders. The urinalysis is cost-effective, timely, non-invasive, and can easily be incorporated into any clinical practice. The ability to identify abnormality across specific areas of the catecholamine pathway, the serotonin pathway, and the GABA pathway allows the integrated healthcare provider to tailor a treatment plan to the specific areas identified. There exists a formulary of 30-40 medicines most integrated healthcare providers call upon for management of depression and other affective disorders. Trials evaluating the impact of such medicines on urinary neurotransmitter assessment among depressed patients would be of tremendous value. ■

References Bravo R, Matito S, Cubero J, Paredes SD, Franco L, Rivero M, Rodríguez AB, Barriga C. Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans. Age (Dordr). 2012 May 24. Carvalho LA, Gorenstein C, Moreno R, Pariante C, Markus RP. Effect of antidepressants on melatonin metabolite in depressed patients. J Psychopharmacol. 2009 May;23(3):315-21.

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Chang RT, Kirby R, Challacombe BJ. Is there a link between BPH and prostate cancer? Practitioner. 2012 Apr;256(1750):13-6 Cook IA. Biomarkers in psychiatry: Potentials, pitfalls, and pragmatics. Primary Psychiatry. 2008;15(3):54-59. April 2008. http://www.primarypsychiatry.com/aspx/articledetail. aspx?articleid=1477 Dasgupta B, Cimmino MA, Maradit-Kremers H et al 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012 Apr;71(4):484-92. Duncan J, Johnson S, Ou XM. Monoamine oxidases in major depressive disorder and alcoholism. Drug Discov Ther. 2012 Jun;6(3):112-22. Eby GA 3rd, Eby KL. Magnesium for treatment-resistant depression: a review and hypothesis. Med Hypotheses. 2010 Apr;74(4):649-60. Fava GA, Ruini C, Rafanelli C. Sequential treatment of mood and anxiety disorders. J Clin Psychiatry. 2005. Nov;66(11):1392-400. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010 Jan 6;303(1):47-53. Fu XY, Lu YR, Wu JL, Wu XY, Bao AM. [Alterations of plasma aspartic acid, glycine and asparagine levels in patients with major depressive disorder] [Article in Chinese]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2012 Mar;41(2):132-8.

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Fullagar S, O’Brien W. Problematizing the neurochemical subject of antidepressant treatment: The limits of biomedical responses to women’s emotional distress. Health (London). 2012 Jun 6. Garrido M, Espino J, González-Gómez D, Lozano M, Barriga C, Paredes SD, Rodríguez AB. The consumption of a Jerte Valley cherry product in humans enhances mood, and increases 5-hydroxyindoleacetic acid but reduces cortisol levels in urine. Exp Gerontol. 2012 Aug;47(8):573-80. Gaynes BN, Rush AJ, Trivedi M, Wisniewski SR, Balasubramani GK, Spencer DC, Petersen T, Klinkman M, Warden D, Schneider RK, Castro DB, Golden RN. A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial. Gen Hosp Psychiatry. 2005 MarApr;27(2):87-96. Genung V. Understanding the neurobiology, assessment, and treatment of substances of abuse and dependence: a guide for the critical care nurse. Crit Care Nurs Clin North Am. 2012 Mar;24(1):117-30. Graefe KH, Friedgen B, Wolfel R, Bossle F, Russ H,Schomig E. 1,1_Diisopropyl-2,4_-cyanine (disprocynium24), a potent uptake 2 blocker, inhibits the renal excretion of catecholamines. Naunyn Schmiedebergs Arch. Pharmacol. 1997;356:115–125. Grossman F, Potter WZ. Catecholamines in depression: a cumulative study of urinary norepinephrine and its major metabolites in unipolar and bipolar depressed patients versus healthy volunteers at the NIMH. Psychiatry Res. 1999;87(1): 21-27. Hamer M, Batty GD, Marmot MG, Singh-Manoux A, Kivimäki M. Anti-depressant medication use and C-reactive protein: results from two population-based studies. Brain Behav Immun. 2011 Jan;25(1):168-73. Hollon SD, Shelton RC, Wisniewski S, Warden D, Biggs MM, Friedman ES, Husain M, Kupfer DJ, Nierenberg AA, Petersen TJ, Shores-Wilson K, Rush AJ. Presenting characteristics of depressed outpatients as a function of recurrence: preliminary findings from the STAR*D clinical trial. J Psychiatr Res. 2006 Feb;40(1):59-69. Holsboer F. How can we realize the promise of personalized antidepressant medicines? Na Rev Neurosci. 2008;9(8): 638-646. Hovelsø N, Sotty F, Montezinho LP, Pinheiro PS, Herrik KF, Mørk A. Therapeutic potential of metabotropic glutamate receptor modulators. Curr Neuropharmacol. 2012 Mar;10(1):12-48. Hughes JW, Watkins L, Blumenthal JA, Kuhn C, Sherwood A. Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women. J.Psychosom. Res. 2004;57(4): 353-358. Kahane A. Urinary Neurotransmitter Analysis as a Biomarker for Psychiatric Disorders. Townsend Letter. January 2009 Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the ‘kindling’ hypothesis. Am J Psychiatry 2000;157:1243–51 Koepsell H, Busch A, Gorboulev V, Arndt P. Structure and Function of Renal Organic Cation Transporters. News Physiol Sci. 1998 Feb;13:11-16. Koslow SH, Maas JW, Bowden CL, Davis JM, Hanin I, Javaid J. CSF and urinary biogenic amines and metabolites in depression and mania. A controlled, univariate analysis. Arch Gen Psychiatry. 1983 Sep;40(9):9991010. Kotzailias N, Marker M, Jilma B. Early effects of paroxetine on serotonin storage, plasma levels, and urinary excretion: a randomized, double-blind, placebo-controlled trial. J.Clin.Psychopharmacol. 2004;24(5): 536-539. Lechin F, van der Dijs B. Central nervous system circuitry and peripheral neural sympathetic activity responsible for essential hypertension. Curr Neurovasc Res. 2006 Nov;3(4):307-25. Lepschy M, Rettenbacher S, Touma C, Palme RG. Excretion of catecholamines in rats, mice and chicken. J Comp Physiol B. 2008 Jul;178(5):629-36. Linnoila M, Miller TL, Bartko J, Potter WZ. Five antidepressant treatments in depressed patients. Effects on urinary serotonin and 5-hydroxyindoleacetic acid output. Arch Gen Psychiatry. 1984 Jul;41(7):688-92.

Lurie S. Psychological issues in treatment of the “chemical imbalance”. Am J Psychother. 1991;45:348-358. Lynn-Bullock CP, Welshhans K, Pallas SL, Katz PS. The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. J Chem Neuroanat. 2004 May;27(2):129-38. Maj M, Pirozzi R, Formicola AM, Bartoli L, Bucci P. Reliability and validity of the DSM-IV diagnostic category of schizoaffective disorder: preliminary data. J Affect Disord. 2000 Jan-Mar;57(1-3):95-8. Marc DT, Ailts JW, Campeau DC, Bull MJ, Olson KL. Neurotransmitters excreted in the urine as biomarkers of nervous system activity: validity and clinical applicability. Neurosci Biobehav Rev. 2011 Jan;35(3):635-44. Moleman P, Tulen J, Blankestijn P, Man in’t Veld A, Boomsma F. Urinary excretion of catecholamines and their metabolites in relation to circulating catecholamines.Six-hour infusion of epinephrine and norepinephrine in healthy volunteers.Arch. Gen. Psychiatry. 1992; 49, 568–572. Moreira TS, Takakura AC, Damasceno RS, Falquetto B, Totola LT, Sobrinho CR, Ragioto DT, Zolezi FP. Central chemoreceptors and neural mechanisms of cardiorespiratory control. Braz J Med Biol Res. 2011 Sep;44(9):883-9. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. Lancet. 1997;349:1498– 504. Nichkova MI, Huisman H, Wynveen PM, Marc DT, Olson KL, Kellermann GH. Evaluation of a novel ELISA for serotonin: urinary serotonin as a potential biomarker for depression. Anal Bioanal Chem. 2012 Feb;402(4):1593-600. Oyebode F, Rastogi A, Berrisford G, Coccia F. Psychotropics in pregnancy: safety and other considerations. Pharmacol Ther. 2012 Jul;135(1):71-7. Okumura T, Nakajima Y, Matsuoka M, Takamatsu T, 1997. Study of salivary catecholamines using fully automated column-switching highperformance liquid chromatography. J. Chromatogr. B Biomed. Sci. Appl. 694, 305–316. Otte C, Neylan TC, Pipkin SS, Browner WS, Whooley MA. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: findings from the Heart and Soul Study. Am J Psychiatry. 2005 Nov;162(11):2139-45. Palazidou E. The neurobiology of depression. British Medical Bulletin. 2012; 101: 127–145 Rozas I. Improving antidepressant drugs: update on recently patented compounds. Expert Opin Ther Pat. 2009 Jun;19(6):827-45. Roy A, Pickar D, Karoum F, Linnoila M. Norepinephrine and its metabolites in cerebrospinal fluid, plasma, and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression.Arch. Gen. Psychiatry. 1988;45, 849–857. Roy A, Pickar D, Douillet P, Karoum F, Linnoila M. Urinary monoamines and monoamine metabolites in subtypes of unipolar depressive disorder and normal controls. Psychol Med. 1986;16(3): 541 546. Roy A, Pollack S. Are cerebrospinal fluid or urinary monoamine metabolite measures stronger correlates of suicidal behavior in depression? Neuropsychobiology. 1994;29(4):164-7. Sato Y, Fujiwara H, Takatsu Y. Cardiac troponin and heart failure in the era of high-sensitivity assays. J Cardiol. 2012 Aug 3. Schwarz E, Bahn S. The utility of biomarker discovery approaches for the detection of disease mechanisms in psychiatric disorders. Br J Pharmacol. 2008;153Suppl 1: S133-S136. Srinivas PR, Kramer BS, Srivastava S. Trends in biomarker research for cancer detection. Lancet Oncol. 2001 Nov;2(11):698-704. Tamatam A, Khanum F, & Bawa, AS. Genetic biomarkers of depression. Indian J Hum Genet. 2012 Jan-Apr; 18(1): 20–33. Waterreus A, Morgan VA, Castle D, Galletly C, Jablensky A, Di Prinzio P, Shah S. Medication for psychosis - consumption and consequences: The second Australian national survey of psychosis. Aust N Z J Psychiatry. 2012 Aug;46(8):762-73.

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The Journal of IHP – Continuing Education successful completion of the questions at the end of this paper has been approved for continuing education by the bddt-n ; 1.0 credit parenteral therapy and by the cnpbc ; one ce hour.

Intravenous Therapies Fish oil based lipid emulsions (FOBLE) Heidi Fritz, MA, ND Research Fellow Canadian College of Naturopathic Medicine hfritz@ccnm.edu Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario L7E1C7 Philip Rouchotas MSc, ND Integrated Healthcare Practitioners Editor-in-Chief philip@ihpmagazine.com Bolton Naturopathic 64 King St W, Bolton, Ontario L7E1C7

Fish oil based lipid emulsions (FOBLE) have an excellent record of safe and effective use, objectively evaluated in over 55 human intervention trials. Critical care hospital settings remain the most thoroughly evaluated areas of their application, however interest in management of flares of chronic inflammatory disorders such as arthritis and psoriasis has begun to emerge. By showcasing the clinical utility of this safe and effective intravenous treatment strategy, it is hoped, progress can be made in adding fish oil to the armament of intravenous therapies at the disposal of integrated healthcare providers.

Introduction Fish derived omega-3 (n-3) fatty acids, specifically eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) are well recognized for their anti-inflammatory effects (Rangel-Huerta 2012). Upon incorporation into the cell membrane, EPA and DHA competitively inhibit production of pro-inflammatory cytokines from arachidonic acid (AA), such as prostaglandin E2 (PGE2), and serve as a substrate for production of less active prostaglandin E3 (PGE3, anti-inflammatory) (Mayer 2006). In addition, EPA and DHA are precursors for the inflammation-resolving mediators appropriately known as resolvins (Calder 2010). The uses of intravenously (IV) administered fish oils, or fish oil based lipid emulsions (FOBLE), are lesser known. Nonetheless, there is a welldeveloped body of research demonstrating impressive clinical benefits associated with use of IV fish oils. The most supported application of IV fish oils is in the critical care setting, however other areas of application have also been investigated. Figure 1 shows the effect of EPA on generation of inflammatory cytokines. A Pubmed search for “intravenous omega-3” on 10 August 2012 yielded 57 clinical trials. Not all of these are included here since some pertain to highly specialized applications, such as liver disease in premature infants, total parenteral (TPN) –related liver disease, endstage renal disease, or biomarker studies such as those investigating effects on antioxidant status. This article includes 18 clinical trials of intravenous omega-3 fatty acids related to the following areas: 1) critical care

(n=13); 2) rheumatoid arthritis (n=2); and 3) psoriasis and inflammatory skin diseases (n=3). Pharmacology The most widely used and well-researched parenteral lipid emulsion featuring omega-3 fatty acids is Omegaven (Fresenius-Kabi, Germany). Omegaven is a 10% fish oil emulsion meaning that it contains 10g refined fish oil per 100mL, including between 1-3g each EPA and DHA (Calder 2010, Fresenius Kabi 2010). Other fish oil based formulations include SMOFLipid 20% (Fresenius-Kabi), which contains 30g total fish oils per 1000mL in combination with soybean oil, medium chain triglycerides, and olive oil (AusPAR 2010, Calder 2010); and Lipoplus (B. Braun, Germany), which contains 20g total fish oil per 1000mL in combination with soybean oil and medium chain triglycerides (B. Braun un-dated product information). Intravenous delivery of n-3 PUFAs has been shown to circumvent the slower n-3 incorporation into phospholipid membranes following oral administration (Carpentier 2010, Roulet 1997, Simeons 2008). Incorporation of EPA into leukocyte and platelet membranes after IV administration occurs within 60 minutes (Carpentier 2010). Similarly, Madsen found that IV administration of 4.1g n-3 PUFAs (polyunsaturated fatty acids) resulted in an increase of levels present in platelet phospholipids at 4 hours, and increased levels in plasma phospholipids at 48 hours, while there was no change in the placebo group (2011). www.ihpmagazine.com l October 2012 71

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A study by Roulet conducted among 10 postoperative patients found that a lipid emulsion with 10% fish oil added resulted in a greater than two-fold increase in the EPA content of platelet phospholipids, and decreased maximal platelet reaction speed (p <0.02) while increasing latency (p <0.002), indicating a less heightened immune response (1997). Importantly, no toxicities, including no increase in postoperative bleeding and no abnormalities in hepatic and renal function, were observed during the fish oil infusion (Roulet 1997). Pradier et al investigated the safety of a bolus IV injection of a medium-chain triglyceride:fish oil emulsion (8:2 ratio) on hemostatic parameters in 12 healthy subjects (2008). No adverse effect was found on 1) occlusion time in response to the ADP (adenosine diphosphate, a platelet activator) or the epinephrine test; 2) levels of certain markers of coagulability, such as fibrinogen, PAC-1, and others, in response to ADP, collagen or thrombin receptor analog peptide six when examined ex vivo. Authors concluded that these results support the hemostatic safety of the IV fish oil emulsion (Pradier 2008). Clinical trials Critical Care: Sepsis and Systemic Inflammatory Response Syndrome (SIRS) In the critical care setting, intravenous supplementation with fish oil is being studied for its powerful immunologic effects (Mayer

2006). In particular, IV fish oil has been shown to decrease the length of hospitalization in patients undergoing abdominal surgery (Jiang 2010), decrease levels of inflammation in patients with sepsis or SIRS (Sungertekin 2011), and decrease complications in post-operative patients (Heller 2006). For years, the standard lipid based emulsion used in patients requiring total or partial parenteral nutrition (TPN, PN) has consisted of soybean oil rich in omega-6 fatty acids (Mayer 2006). It was subsequently found however that high amounts of omega-6 fatty acids may in fact harmfully suppress immune function, resulting in increased rates of infection (Calder 2010, Nordenstrรถm 1979, Snydman 1982). Conversely, newer emulsions such as Omegaven containing 10% (w/v) fish oil have been shown to beneficially impact immune function in healthy (Pittet 2010, Pluess 2007) and hospitalized patients (Wei 2010). In healthy patients, Omegaven has been shown to blunt the immune response to the endotoxin lipopolysaccharide (LPS) (Pittet 2010, Pluess 2007). Since bacterial-derived LPS acts as a trigger eliciting many of the harmful symptoms of infection and/ or sepsis essentially effected by the immune system, such as fever, systemic inflammation, and shock, reducing this reaction is considered beneficial in these patients. In addition, Pluess et al found that Omegaven blunted the effects of LPS on fever and the neuroendocrine response to infection (2007).

Figure 1. How EPA Impacts Synthesis of Inflammatory Cyotkines (adapted from Mayer 2006). - Thromboxane A2

- Leukotriene B4 Lipoxins

Arachidonic Acid Eicosapentaenoic Acid

3-Series prostaglandins

- Leukotriene C4

5-Lipoxygenase

Cyclooxygenase

- Prostaglandin I2

5-Series leukotrienes Resolvins

- Thromboxane A3

- Leukotriene B5

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The Journal of IHP – Continuing Education Table 1. Critical Care: Uses in Sepsis, Systemic Inflammatory Response Syndrome (SIRS),& Post-operative Patients Reference

Design

Intervention

Outcome

Han 2012

RCT; N=38 patients in SICU after major surgery receiving PN

FOBLE (Omegaven 0.2g/ kg daily) OR same PN without fish oil n-3’s x7d post-op

↓in IL-1, IL-8, and IFN-γ on post-op day 4 (p<0.05), and IL-1, IL-8, IFN-γ, IL-6, and TNF-α on post-op day 7 (p<0.05) in n-3 group. NS ↓in post-op liver dysfunction (control 50% vs n-3 33.3%) and infection rate (41.7% vs 27.8%).

Sungertekin 2011

RPCT; N=20 sepsis + 20 SIRS patients receiving PN

FOBLE (Omegaven 0.6g/ kg) OR PN with MCT/LCT but not fish oils x 7d

Sepsis groups who did not receive n-3s had ↑grades of liver steatosis on ultrasound at days 7 and 10 (P<0.05) compared to the n-3 group. TNF-α and IL-6 levels were higher in control patients compared to the n-3 group on day 7.

Khor 2011

RDBPCT; N=28 patients with severe sepsis

10% FOBLE (Omegaven) OR saline infusion placebo

↓APACHE II score on days 3, 5 & 7 (p<0.05 for all); ↓APACHE III (p = 0.028) and Simplified Acute Physiology Score II (p = 0.019) on day 7. No significant difference in length of hospital stay.

RCT; N=206 patients completed surgery for gastrointestinal or colonic cancer

10% FOBLE (Omegaven 0.2g/kg) OR isocaloricisonitrogenous infusion based on soybean oil only over 2024h daily x7d

The n-3 group had:

RCT; N= 60 patients with severe acute pancreatitis

10% FOBLE (Omegaven 0.2g/kg) x7d plus conventional therapy OR conventional therapy only

In the n-3 group:

RDBPCT; N= 42 patients undergoing radical colorectal cancer resection on TPN

10% FOBLE (Omegaven 0.2g/kg) OR standard soybean oil based TPN x 7d

The n-3 group had:

Wichmann 2007

RDBPCT; N= 256 patients undergoing major abdominal surgery receiving PN

2% FOBLE (Lipoplus) OR emulsion without fish oil (Intralipid) x5d post-op

In the n-3 group, plasma levels of EPA, leukotriene B5, and antioxidant content were significantly increased, and length of hospital stay of was 21% shorter (17.2 vs. 21.9 days; p = .0061).

Tappy 2006

RCT; N= 24 SICU patients on PN

10% FOBLE (Omegaven) OR a standard soybean oil emulsion

Total energy expenditure was significantly lower in patients receiving n-3 fatty acids (0.015+/-0.001 vs. 0.019+/-0.001 kcal/kg/min, P<0.05).

Mertes 2006

RDBPCT; N= 199 postoperative patients on TPN (abdominal or thoracic surgery)

20% FOBLE (SMOFlipid, 30g fish oil/L) or standard soybean oil emulsion (Lipovenoes 20%) (1.5g/ kg/d x5d)

Trend towards a reduced length of hospital stay with SMOFlipid (15.7 +/- 6.3 vs. 17.8 +/- 13.2 days).

Jiang 2010

Xiong 2009

Liang 2008

↓infectious complications (4 vs 12; P= 0.066); ↓incidence of SIRS (4 vs 13; P = 0.039); ↓hospital stay (mean 15vs 17 days; P = 0.041). No severe adverse events.

↓APACHE-II scores compared to controls (P<0.05); ↓fluid equilibrium time (5.1+/-2.2 days vs 8.4+/-2.3 days); ↓ SIRS scores and the SIRS state resolved after the 4th day; ↓TNF-alpha (P<0.05).

Greater reduction in IL-6 and TNF-alpha (p<0.05). ↑CD4+/CD8+ (P = 0.035). Shorter postoperative hospital stay (17.45 +/- 4.80 d vs 19.62 +/- 5.59 d, P = 0.19).

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RDBPCT; N=33 post-op patients on TPN (major abdominal surgery)

20% FOBLE (SMOFlipid, 30g fish oil/L) or standard soybean oil emulsion (Lipovenoes 20%) (1.5g/ kg/d x5d)

Phospholipid ratio of EPA/AA ↑with SMOFLipid but not the control emulsion.

Antebi 2004

RDBPCT; N= 20 stressed ICU patients on TPN

FOBLE (SMOF, 15% fish oil) OR standard soybean oil-based emulsion (LIPOVEN) daily x 5d

↑liver enzymes and phospholipids/apo A1 ratio in both groups, however, the increases were lower in the SMOF group, and was non-significant for the CRP level and the ALT activity.

Mayer 2003A

RCT; N=21 critical care patients with sepsis requiring PN

10% FOBLE (Omegaven), OR conventional soybean oil based emulsion (Lipoven) x 5d

Before lipid infusion therapy, AA was greatly increased. Within 2 days of fish oil infusion, free n-3 fatty acids increased, and the n-3/n-6 ratio was reversed. Generation of proinflammatory cytokines was markedly amplified during n-6 and suppressed during n-3 lipid application.

Mayer 2003B

Open label RCT; N=10 patients with sepsis requiring PN + 8 healthy controls

10% FOBLE (Omegaven), OR conventional soybean oil based emulsion (Lipoven) x10d

At baseline levels of plasma free fatty acids including AA were elevated. Neutrophils isolated from septic patients showed reduced responsiveness to ex vivo stimulation. With the omega-6 lipid infusion,these abnormalities persisted or worsened. In response to n-3’s a shift occurred in the n-3/ n-6 ratio, and neutrophil function improved.

Grimm 2006

↓Length of hospital stay with SMOFlipid (13.4 +/- 2.0 vs. 20.4 +/- 10.0 days, p < 0.05).

Key: APACHE Acute Physiology and Chronic Health Evaluation score; ICU intensive care unit; IL interleukin; LCT long chain triglyceride; MCT medium chain triglyceride; NS non significant; PN parenteral nutrition; SICU surgical intensive care unit; TPN total parenteral nutrition.

Table 1 presents a summary of 13 human trials investigating use of IV fish oil in critical care patients for outcomes related to sepsis, systemic inflammatory response syndrome (SIRS, syndrome secondary to severe infection), hospitalization, and mortality. These studies show that use of FOBLE may: improve post-operative liver function and rates of infection (Han 2012); improve Acute Physiology and Chronic Health Evaluation (APACHE) scores, a disease severity scoring system used in ICU settings, in patients with severe sepsis (Khor 2011) and pancreatitis (Xiong 2009); prevent infectious complications and incidence of SIRS, and reduce hospital stays in cancer patients undergoing major abdominal surgery (Jiang 2008, Liang 2008). In addition, a 2010 meta analysis reviewed six RCTs conducted in Europe and Asia that compared parenteral nutrition with or without fish oil emulsion in postoperative patients (Wei 2010). Although in this study there was no significant impact on mortality, use of fish oil was associated with a significant reduction in infectious complications (relative risk RR 0.49, 95% confidence interval 0.26-0.93, P=0.03). The length of hospital stay was non-significantly decreased by over 3 days, with a decrease in 2.07 days in the intensive care unit (Wei 2010).

A prospective study of Omegaven among 661 patients with major abdominal surgery, abdominal sepsis, nonabdominal sepsis, serious trauma, or other diagnoses, and receiving TPN for three days or more, in 82 German hospitals, found that use of FOBLE resulted in: favorable effects on survival, infection rates, and length of stay, when administered in doses between 0.1 and 0.2 g/kg/day (Heller 2006). At doses of 0.15-0.2 g/kg/day, antibiotic requirements were 26% lower when compared with doses of <0.05 g/kg/day. After peritonitis and abdominal sepsis, the fish oil dose for minimizing length of intensive care unit stay was 0.23 g/kg/day (Heller 2006). Rheumatoid Arthritis Table 2 summarizes two human trials investigating IV fish oil emulsions in the treatment of active rheumatoid arthritis (RA) (Bahadori 2010, Leeb 2006). In a randomized, double blind, placebo controlled trial, Bahadori administered IV fish oil 0.2g/kg daily for 14 days in patients with moderate to severe RA, followed by oral fish oil for 20 weeks, and found that after only one week, as well as after two weeks, swollen joint count was significantly lower in the fish oil group (2010). This effect persisted to the end of 20 weeks/ end of oral

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The Journal of IHP – Continuing Education Table 2. Trials of Intravenous Fish Oil in Rheumatoid Arthritis Reference

Design

Intervention

Outcome

Bahadori 2010

RDBPCT; N= 23 patients with moderate to severe RA

10% FOBLE (Omegaven, 0.2g/kg) OR 0.9% saline infusion daily x14d, followed by 0.05g fish oil/ kg or placebo taken orally x20wk

Swollen joint count was significantly lower in the n-3 group compared with the placebo group after 1 and 2 weeks (P<.05). Tender joint count was NS lower in the n-3 group. At the end of oral treatment (20wk), both swollen and tender joint counts were significantly lower in the omega-3 FA group.

Leeb 2006

Open pilot study; N=34 patients with severe active RA (DAS28 score ≥4) (Fransen2009)

10% FOBLE (Omegaven, 0.1–0.2 g/kg) daily x7d

There was no change in DAS28 over the 7day treatment period, however there was a significant reduction thereafter from week 1 to ~1month (P< .001). 56% of patients achieved a reduction of the DAS28 > 0.6 (predefined endpoint) after 7days; 27% had improvement >1.2. Response to treatment, defined as 20 and 50% responses by the ACR criteria, were seen in 29 and 12% of patients, respectively after 1wk.

Key: ACR American College of Rheumatology (ACR) response criteria; DAS28 Disease activity score including a 28 joint count;

supplementation as well. Leeb conducted an open pilot trial in patients with severe RA, administering 0.1-0.2g/ kg fish oil daily for seven days; there was a significant reduction in disease severity ratings over time (p<0.001) and tolerability was rated as “excellent” (Leeb 2006). Intravenous fish oil may represent a safe and rapidly acting strategy to control severe acute RA. Dermatology: Psoriasis and Atopic Dermatitis Table 3 summarizes three human trials investigating IV fish oil emulsions for the treatment of psoriasis or atopic dermatitis (Grimminger 1993, Mayser 2002, Mayser 1998). In patients with moderate to severe atopic dermatitis, IV fish oil for 10 days resulted in significant improvement in disease severity (visible by day 6) (p<0.05) compared to placebo (Mayser 2002). An earlier study by the same team examined patients hospitalized for chronic plaque type psoriasis (Mayser 1998). Treatment with Omegaven for 14 days resulted in significant reduction in the Psoriasis Activity Severity Index (PASI) (p=0.048) in the fish oil group compared to controls. A total of 16 of 43 patients (37%) in the fish oil group experienced a clinical response, defined as a reduction in PASI of 50% or greater, compared to 23% in the control group. Finally, Grimminger found that IV fish oil improved disease severity between 4576% depending on the scoring measure (p<0.05 for all)

in hospitalized patients with psoriasis involving 10% or more of their body surface area (1993). Remarkably, the treatment effect was evident within four to seven days of daily IV fish oil administration. Finally, IV fish oils have been shown to reduce cardiac arrhythmias (Heidt 2009) and improve PN-associated liver disease (Le 2010), however these applications are beyond the scope of this paper. Conclusion Intravenously administered fish-derived omega-3 fatty acids have been studied for a number of indications including the treatment and prevention of serious infection and SIRS in hospitalized patients; treatment of acute rheumatoid arthritis; inflammatory skin conditions including psoriasis and atopic dermatitis; as well as the prevention of arrhythmias and liver disease. In these populations, IV fish oil has been demonstrated to improve immune function, shorten hospitalization, reduce mortality, and significantly decrease disease activity. In some cases, the rate of disease improvement is rapid, occurring within the first week of treatment. Although parenteral fish oil emulsions are not currently available to NDs, we hope that access to this safe and efficacious agent will be broadened in the future. ■ www.ihpmagazine.com l October 2012 75

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Table 3. Psoriasis and Atopic Dermatitis Reference

Design

Intervention

Outcome

Mayser 2002

RDBPCT; N=22 patients hospitalized for moderate-to-severe atopic dermatitis

10% FOBLE (Omegaven, 100 mL 2x/d as 120minute peripheral infusion) OR conventional soybean oil based lipid emulsion x10d. Emollients only were allowed topically.

Marked improvement from baseline was seen in both groups but was more pronounced (p < .05) in the n-3 group. With response defined as a ↓in disease severity score of ≥50%, 63.6% receiving n-3 and 11.1% receiving n-6 experienced a response. This was significant on days 9 to 11 (p <0.05) but not in the posttreatment phase. Authors describe relapse in some patients apparently treated subsequently with n-3 and psoralene-ultraviolet A (PUVA) infusion, but this is very poorly described.

Mayser 1998

RDBPCT; N= 83 patients hospitalized for chronic plaquetype psoriasis with severity score ≥15 on PASI

FOBLE (Omegavenous; 200 ml/d with 4.2g EPA+DHA) OR a conventional soybean oil based emulsion (Lipovenous; EPA+DHA <0.1g/100 ml) x14d

Total PASI score ↓by 11.2 +/- 9.8 in the n-3 group and by 7.5 +/- 8.8 in the n-6 group (p = 0.048). Response (decrease in PASI ≥50%) was seen in 37% of patients receiving n-3 and 23% of those receiving n-6.

Grimminger 1993

RDBPCT; N=20 patients hospitalized for acute guttate psoriasis with ≥10% body surface area involvement

FOBLE (Omegavenous; 50mL 2x daily with 2.1g EPA+ 21g DHA) OR a conventional soybean oil based emulsion (Lipovenous; EPA+DHA <0.1 g/100 ml) x10d

The n-6 group had a 16-25% improvement from baseline within 10 days. In contrast, disease severity ↓by 45% and 76% within 10 days (P < 0.05 for each variable) in the n-3 group.

Key: PASI Psoriasis Area and Severity Index; RCT randomized controlled trial; RDBPCT randomized double blind placebo controlled trial; References Antébi H, Mansoor O, Ferrier C, Tétégan M, Morvan C, Rangaraj J, Alcindor LG. Liver function and plasma antioxidant status in intensive care unit patients requiring total parenteral nutrition: comparison of 2 fat emulsions. JPEN J Parenter Enteral Nutr. 2004 May-Jun;28(3):142-8. AusPAR: Australian Public Assessment Report for SMOFLipid. Product Information. June 2010. www.tga.gov.au/pdf/auspar/ausparsmoflipid.pdfAccessed 29 August 2012. Bahadori B, Uitz E, Thonhofer R, Trummer M, Pestemer-Lach I, McCarty M, Krejs GJ. Omega-3 Fatty acids infusions as adjuvant therapy in rheumatoid arthritis.JPEN J Parenter Enteral Nutr. 2010 Mar-Apr;34(2):151-5. B. Braun. Clinical Nutrition Short Guide, Lipoplus Product Information. http://www.bbraun.com/documents/Knowledge/Short_ Guide_Clinical_Nutrition.pdf Accessed 29 August 2012. Calder PC, Jensen GL, Koletzko BV, Singer P, Wanten GJ. Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions. Intensive Care Med. 2010 May;36(5):735-49. Calder PC. Hot topics in parenteral nutrition. Rationale for using new lipid emulsions in parenteral nutrition and a review of the trials performed in adults. ProcNutr Soc. 2009 Aug;68(3):252-60.

Carpentier YA, Hacquebard M, Portois L, Dupont IE, Deckelbaum RJ, Malaisse WJ. Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans. Am J ClinNutr. 2010 Apr;91(4):875-82. de Meijer VE, Gura KM, Meisel JA, Le HD, Puder M. Parenteral fish oil monotherapy in the management of patients with parenteral nutrition-associated liver disease. Arch Surg. 2010 Jun;145(6):547-51. Fallon EM, Le HD, Puder M. Prevention of parenteral nutritionassociated liver disease: role of omega-3 fish oil. CurrOpin Organ Transplant. 2010 Jun;15(3):334-40. Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am. 2009 Nov;35(4):74557, vii-viii. Fresenius Kabi New Zealand Ltd. Consumer Medicine Information for Omegaven. July 2010. www.medsafe.govt.nz/consumers/cmi/o/ omegaven.pdfAccessed 29 August 2012. Grimm H, Mertes N, Goeters C, Schlotzer E, Mayer K, Grimminger F, Fürst P. Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients. Eur J Nutr. 2006 Feb;45(1):55-60. Grimminger F, Mayser P, Papavassilis C, Thomas M, Schlotzer E, Heuer KU, Führer D, Hinsch KD, Walmrath D, Schill WB, et al. A double-blind, randomized, placebo-controlled trial of n-3 fatty

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The Journal of IHP – Continuing Education acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile.ClinInvestig. 1993 Aug;71(8):634-43. Han YY, Lai SL, Ko WJ, Chou CH, Lai HS.Effects of fish oil on inflammatory modulation in surgical intensive care unit patients. NutrClinPract. 2012 Feb;27(1):91-8. Heidt MC, Vician M, Stracke SK, Stadlbauer T, Grebe MT, Boening A, Vogt PR, Erdogan A. Beneficial effects of intravenously administered N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a prospective randomized study. ThoracCardiovasc Surg. 2009 Aug;57(5):276-80. Heller AR, Rössler S, Litz RJ, Stehr SN, Heller SC, Koch R, Koch T. Omega-3 fatty acids improve the diagnosis-related clinical outcome. Crit Care Med. 2006 Apr;34(4):972-9. Jiang ZM, Wilmore DW, Wang XR, Wei JM, Zhang ZT, Gu ZY, Wang S, Han SM, Jiang H, Yu K. Randomized clinical trial of intravenous soybean oil alone versus soybean oil plus fish oil emulsion after gastrointestinal cancer surgery. Br J Surg. 2010 Jun;97(6):804-9. Khor BS, Liaw SJ, Shih HC, Wang LS. Randomized, double blind, placebo-controlled trial of fish-oil-based lipid emulsion infusion for treatment of critically ill patients with severe sepsis. Asian J Surg. 2011 Jan;34(1):1-10. Le HD, de Meijer VE, Zurakowski D, Meisel JA, Gura KM, Puder M. Parenteral fish oil as monotherapy improves lipid profiles in children with parenteral nutrition-associated liver disease. JPEN J Parenter Enteral Nutr. 2010 Sep-Oct;34(5):477-84. Leeb BF, Sautner J, Andel I, Rintelen B. Intravenous application of omega-3 fatty acids in patients with active rheumatoid arthritis. The ORA-1 trial.An open pilot study. Lipids. 2006 Jan;41(1):29-34. Liang B, Wang S, Ye YJ, Yang XD, Wang YL, Qu J, Xie QW, Yin MJ. Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients.World J Gastroenterol. 2008 Apr 21;14(15):2434-9. Madsen T, Christensen JH, Thøgersen AM, Schmidt EB, Toft E. Intravenous infusion of n-3 polyunsaturated fatty acids and inducibility of ventricular tachycardia in patients with implantable cardioverter defibrillator. Europace. 2010 Jul;12(7):941-6. Madsen T, Christensen JH, Toft E, Aardestrup I, LundbyeChristensen S, Schmidt EB. Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease. JPEN J Parenter Enteral Nutr. 2011 Jan;35(1):97-106. Mayer K, Schaefer MB, Seeger W. Fish oil in the critically ill: from experimental to clinical data. CurrOpinClinNutrMetab Care. 2006 Mar;9(2):140-8. Mayer K, Gokorsch S, Fegbeutel C, Hattar K, Rosseau S, Walmrath D, Seeger W, Grimminger F. Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis. Am J RespirCrit Care Med. 2003 May 15;167(10):1321-8. A Mayer K, Fegbeutel C, Hattar K, Sibelius U, Krämer HJ, Heuer KU, Temmesfeld-Wollbrück B, Gokorsch S, Grimminger F, Seeger W. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation. Intensive Care Med. 2003 Sep;29(9):1472-81. B Mayser P, Mayer K, Mahloudjian M, Benzing S, Krämer HJ, Schill WB, Seeger W, Grimminger F. A double-blind, randomized, placebocontrolled trial of n-3 versus n-6 fatty acid-based lipid infusion in atopic dermatitis. JPEN J Parenter Enteral Nutr. 2002 MayJun;26(3):151-8. Mayser P, Mrowietz U, Arenberger P, Bartak P, Buchvald J, Christophers E, Jablonska S, Salmhofer W, Schill WB, Krämer HJ, Schlotzer E, Mayer K, Seeger W, Grimminger F. Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis:

results of a double-blind, randomized, placebo-controlled, multicenter trial. J Am AcadDermatol. 1998 Apr;38(4):539-47. Mertes N, Grimm H, Fürst P, Stehle P. Safety and efficacy of a new parenteral lipid emulsion (SMOFlipid) in surgical patients: a randomized, double-blind, multicenter study. Ann NutrMetab. 2006;50(3):253-9. Park KT, Nespor C, Kerner J Jr. The use of Omegaven in treating parenteral nutrition-associated liver disease. J Perinatol. 2011 Apr;31Suppl 1:S57-60. Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chioléro RL. Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med. 2007 May;33(5):789-97. Nordenström J, Jarstrand C, Wiernik A. Decreased chemotactic and random migration of leukocytes during Intralipid infusion. Am J Clin Nutr. 1979 Dec;32(12):2416-22. Pradier O, Portois L, Malaisse WJ, Carpentier YA. Hemostatic safety of the bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion. Int J Mol Med. 2008 Sep;22(3):301-7. Rangel-Huerta OD, Aguilera CM, Mesa MD, Gil A. Omega-3 longchain polyunsaturated fatty acids supplementation on inflammatory biomakers: asystematic review of randomised clinical trials. Br J Nutr. 2012 Jun;107Suppl2:S159-70. Roulet M, Frascarolo P, Pilet M, Chapuis G. Effects of intravenously infused fish oil on platelet fatty acid phospholipid composition and on platelet function in postoperative trauma. JPEN J Parenter Enteral Nutr. 1997 Sep-Oct;21(5):296-301. Schrepf R, Limmert T, Claus Weber P, Theisen K, Sellmayer A. Immediate effects of n-3 fatty acid infusion on the induction of sustained ventricular tachycardia. Lancet. 2004 May 1;363(9419):1441-2. Simoens CM, Deckelbaum RJ, Massaut JJ, Carpentier YA. Inclusion of 10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids. Am J ClinNutr. 2008 Aug;88(2):282-8. Snydman DR, Murray SA, Kornfeld SJ, Majka JA, Ellis CA. Total parenteral nutrition-related infections. Prospective epidemiologic study using semiquantitative methods. Am J Med. 1982 Nov;73(5):695-9. -Omega-6 is not mentioned anywhere in this article Sungurtekin H, Değirmenci S, Sungurtekin U, Oguz BE, Sabir N, Kaptanoglu B. Comparison of the effects of different intravenous fat emulsions in patients with systemic inflammatory response syndrome and sepsis. NutrClinPract. 2011 Dec;26(6):665-71. Tappy L, Berger MM, Schwarz JM, Schneiter P, Kim S, Revelly JP, Chioléro R. Metabolic effects of parenteral nutrition enriched with n-3 polyunsaturated fatty acids in critically ill patients.ClinNutr. 2006 Aug;25(4):588-95. Tomsits E, Pataki M, Tölgyesi A, Fekete G, Rischak K, Szollár L. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition. J PediatrGastroenterolNutr. 2010 Oct;51(4):514-21. Wei C, Hua J, Bin C, Klassen K. Impact of lipid emulsion containing fish oil on outcomes of surgical patients: systematic review of randomized controlled trials from Europe and Asia. Nutrition. 2010 May;26(5):474-81. Wichmann MW, Thul P, Czarnetzki HD, Morlion BJ, Kemen M, Jauch KW. Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion (Lipoplus, MLF541): data from a prospective, randomized, multicenter trial. Crit Care Med. 2007 Mar;35(3):700-6. Xiong J, Zhu S, Zhou Y, Wu H, Wang C. Regulation of omega-3 fish oil emulsion on the SIRS during the initial stage of severe acute pancreatitis. J HuazhongUnivSciTechnolog Med Sci. 2009 Feb;29(1):35-8.

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Questions 1. Fish oil based lipid emulsion, aka FOBLE, has been evaluated in RCTs for which of the following areas of application: a) rheumatoid arthritis b) infection c) post abdominal surgery d) all of the above 2. The most widely researched parenteral lipid emulsion featuring omega-3 fatty acids is SMOFLipid 20% a) true b) false 3. Which of the following is true about FOBLE pharmacology? a) IV delivery circumvents the slower n-3 incorporation rate into phospholipid membranes following oral administration b) Incorporation of EPA into leukocyte and platelet membranes after IV administration occurs within 30 minutes c) FOBLE has been shown to increase risk of bleeding post-operatively d) All of the above 4. In the critical care setting, FOBLE has been shown to: a) decrease levels of inflammation in patients with sepsis or SIRS b) decrease complications including infection rates in postoperative patients c) decrease the length of hospitalization in patients undergoing abdominal surgery d) all of the above 5. FOBLE has been shown to reduce the immune response to LPS, which may increase risk of serious infections. a) true b) false

6. According to a 2010 meta analysis including six RCTs conducted in Europe and Asia and parenteral nutrition with omega-3 oils was associated with: a) significant 50% reduction in mortality, RR 0.50. b) significant reduction in infectious complications, RR 0.49 c) highly significant reduction in the length of hospital stay, with a decrease of over 3 days overall, and a decrease in 2.07 days in the intensive care unit. d) all of the above 7. A German prospective study of Omegaven found that in patients hospitalized for major abdominal surgery, sepsis, or serious trauma, FOBLE doses of 0.15-0.2 g/ kg/day, Omegaven reduced antibiotic requirements 26%, compared with lower doses of <0.05 g/kg/day. a) true b) false 8. The same study found that after peritonitis and abdominal sepsis, FOBLE reduced the length of intensive care unit stay when given at doses of 0.23 g/kg/day. a) true b) false 9. FOBLE has been shown to benefit moderate to severe rheumatoid arthritis. The length of time required to obtain an effect appears to be: a) approximately â&#x2030;Ľ1 week b) approximately â&#x2030;Ľ2 weeks c) approximately 1 month d) none of the above 10. FOBLE has been demonstrated to improve which of the following chronic inflammatory skin condition? a) psoriasis b) vitiligo c) eczema d) a and c e) b and c

Fax or email answers to: 416.703.6392 or philip@ihpmagazine.com Name: Address: City: Province: Postal Code: Phone: Email: Fax: Practice Registration #:

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PRODUCT MONOGRAPH Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. Without treatment, AGA is progressive, and causes social distress in many affected men and women (Sinclair 1998). Bio-Fen Plus contains extracts of fenugreek seeds, saw palmetto berries and flax lignans, as well as greens+ specific vitamins. O Each ingredient is known to possess inhibitors of the enzyme 5-reductase. These inhibitors are responsible for relieving symptoms associated with hereditary AGA. greens+ O is a new, organic greens product designed by Genuine Health to be both hypoallergenic and vegan, so as to be most appropriate for individuals with allergies, intolerances, or One ofrestrictions. the primary causes hairfrom loss75 is to a high level ofingredients; the male ishormone dihydrotestosterone within thecontaining hair follicle (Vierhapper, other dietary greens+ O isof made 80% organic soy- glutenwheat- and dairy free;(DHT) and is 100% vegan, no animal products.2001). greens+ O Forallpeople with AGA, their follicles have a greater of androgen receptors to Owhich DHT 5--reductase catalyzes the carrot, enzymatic contains the important phytochemicals included in the greens+number original formula; in addition, greens+ features selectattaches. new additions including organic spirulina, apple, chia, conversion testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998). and broccoli sprout of extracts. Organic Vitamins SawSpirulina palmetto (Serenoa repens) Spirulina is a nutrient-rich blue-green microalgae enzymatic pigments. Theseinhibitor include the green pigmentstudy Chlorophyll, the bluewho pigment Phycocyanin, red pigment In a Polish of 46 women had symptoms of the diffuse alopecia,Porphyrin, calcium the Standardized (lipophillic) Serenoa extractrich has in been found to be a potent yellowofpigment Xanthophyll and the orange pigment also dose contains omega-3 pantothenate and omega-6 fatty glycolipids and shown possess was acids orallyplus administered twicesulfolipids. a day in Spirulina doses of has 100been mg for fourtoto 5-reductase, resulting in decreased tissue Carotene. DHT. AnSpirulina open-label, response antioxidant, anti-inflammatory immune-modulating (Hirahashi Mau 2005, Nielsen andand possible ergogenic (Kalafati from controlled five2010), months, vitamin B6 wasactivity injected every 2010) day forbased 20 toon30evidence days and repeated study was conducted on activity, 42 healthy males to determine the effect2002, of a combination humanoftrials. Two trials by Mao (2005) (2008) found thatextract supplementation of inflammatory cytokines and symptoms of allergicthat rhinitis. againimproved after six levels months (Brzeziska-Wcisło 2001). It was determined vitamin carotenoid astaxanthin and and saw Cingi palmetto berry lipid on DHTwith andSpirulina B6 administered parenterally for a few weeks induces improvement in the hair testosterone levels (Angwafor 2008). The men were divided into two groups: Organic Carrot condition in a subset of women and reduces hair loss. one group received 800 mg/day of the combination supplement and the other Organic status is of importantance for carrots because some carrots have been found to contain high levels of triazophos, an organophosphorous pesticide (Hamey 1999). Carrots group received 2000 mg/day of the supplement for 14 days. ANOVA-RM showed contain pro-vitamin A carotenes (alpha- and beta-carotene) as well as non-vitamin A precursors such as astaxanthin. According to data from a recent 10-year prospective study from the significant within-group increases in serum total testeosterone and significant Netherlands, intake of orange/ yellow vegetables (predominantly carrots) was strongly protective against cardiovascular disease (Oude 2011). Medicinal Ingredients Dose Per Capsule decreases in serum DHT from baseline in both dose groups (P=0.05). There was no significant difference between dose groups with regard to the increase of Fenugreek (Trigonella foenum graecum) Organic Apple 260 mg testeosterone or the decrease of DHT; therefore both doses were effective (Angwafor seed extract The soluble fiber content of Apple fibre, pectin, cleanses the intestinal tract and promotes cardiovascular health by4:1 binding excess cholesterol and removing it from the bowel (Knopp 2008). 1999). It also helps to block the absorption of other toxins such as hormone and metabolic byproducts that are excreted through the bowels. In patients with blood glucose dysregulation, Saw palmetto berry extract mg research has identified pectin fiber can reduce fasting glucose by slowing gastric emptying and slowing the absorption of sugars from the intestine (Pouteaucontaining 2010). In addition,160 laboratory study tested liposterolic extract of peel Serenoa repens to(LSESr) and betafree acids over aAnother dozen compounds called triterpenoids in apple that appear inhibit growth of human45% cancer cellsfatty in vitro (He 2008). These constituents may contribute to the anticancer sitosterol in the treatment of males (23-64 years of age) with mild to moderate AGA. activities of whole apples. Flax lignans, standardized to 20% Six of 10 (60%) subjects were rated as improved at the final visit, thus establishing 100 mg secoisolariciresinol diglucoside (SDG) the effectiveness of 5-reductase inhibitors against AGA (Prager 2002). Chronic Organic Chia Seed inflammation of the hair follicle is considered to be a contributing factor for AGA. A Salvia hispanica has historically been a staple of the ancient Aztec diet. Research at the University of Toronto has found that supplementation seed (Vuksan D-calcium pantothenate (Vitamin B5)with chia10.40 mg 2007). Patients Chittur et al experienced sought to determine whether blockade inflammation (n=20)study givenby34g chia daily a reduction in systolic bloodofpressure (SBP) ofusing 6.3 +/- 4 mmHg (P < 0.001), and high-sensitivity C-reactive protein (hs-CRP) (mg/l) of 40 +/and(Vuksan two anti-inflammatory agents (carnitine and thioctic acid) could alter 1.6% LSESr (P = 0.04) 2007). Niacinamide (Vitamin B3) 10.25 mg the expression of molecular markers of inflammation (Chittur 2009). It was found Pyridoxine HCl (Vitamin B6) 2 mg thatBroccoli the combination Organic Sprouts suppressed lipopolysaccharide-activated gene expression of chemokines associated withthat pathways involved in inflammation andenzymes apoptosis. Broccoli is rich in phytochemicals can upregulate Phase II detoxification in the body (Latte 2011, Riedl 2009). These include 3 glucosinolate phytonutrients - glucoraphanin, Riboflavin (Vitamin B2) 1.58 mg The studyand concluded that and 5-alpha reductase (ITCs) inhibitors in combination with gluconasturtiian, glucobrassicinisothiocyanates metabolized from glucosinolates, that regulate these enzymes. Consumption of broccoli by smokers has been found to reduce blockade inflammatory processes a new two-pronged with approach markers of DNAofdamage and DNA breakagecould (Riso represent 2010, 2009). Supplementation broccoli hasFolic been acid shown to reduce oxidative stress in patients with0.095 diabetes (Bahadoran 2011). mg in the treatment of AGA. Sunflower Lecithin Biotin 400 mcg Despite suggestions that lecithin provides little nutritional value in a multi-ingredient green food formula, product specific research has demonstrated that lecithin is a key antioxidant Fenugreek Seeds Ingredients withinFenugreek this formula. When lecithin removed from steroid the formula, theresterols, was a significant in the antioxidant capacity of greens+ (Roa 2010). Indeed, lecithin itself may account for seeds contain 5%was to 30% protein, saponins, flavonoidsdeclineNon-Medicinal 15% of thealkaloids greens+ antioxidant activity. For this Genuine Health has included and (notably trigonelline andreason, choline). Steroid saponins bind lecithin and from the allergen-free source, sunflowers, in greens+ O. Inert microcrystalline cellulose and vegetable-based magnesium eliminate extra cholesterol and hormones in the body; DHT is made from stearate in a veggie-based capsule Tabletestosterone, 1. Medicinal Ingredients 7.6g (8.8 acaid mango) serving which is in turn isper made from cholesterol. Therefore, when excess References cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 Bahadoran Z, Mirmiran P, Hosseinpanah F, Hedayati M, Hosseinpour-Niazi S, Azizi F. Broccoli sprouts reduce oxidative Organic spirulina (Arthrospira platensis) 1450mg in type 2 diabetes: a randomized double-blind clinical trial. adult dose: One capsule per Eur dayJ Clin Nutr. 2011. 65(8):972-7. adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for stressRecommended Organic carrot (Daucus carrota) 1200mg one month, higher levels of consumption resulted in a significant reduction in total Cingi C, Conk-Dalay M, Cakli H, Bal C. The effects of spirulina on allergic rhinitis. Eur Arch Otorhinolaryngol. 2008 Oct;265(10):1219-23. cholesterol and (Appleboost low-density lipoprotein (LDL) levels (Sowmya 1999). 1200mg Organic apple peel ®) Sunflower lecithin 1100mg Flax lignans Flax reduces the amount of DHT produced by reducing cholesterol levels in the Organic chia seed (Salvia hispanica L) 400mg body. A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed Organic alfalfa grass (Medicago sativa)total and LDL-cholesterol concentrations 383mg(Pan significantly reduces circulating 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L Organic chlorella (cracked cell) (Chlorella vulgaris) 300mg (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), Organic brown rice (Oryza sativa) 300mgand respectively. Significant reductions were observed with whole flaxseed (-0.21 -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) Organic red beet root (Beta vulgaris) 200mg supplements (Pan 2009). Organic broccoli sprout (nonGMO) (Brassica oleracea italica) 200mg Organic broccoli (Brassica oleracea) References

200mg

Hamey, P. Y. and Harris, C. A. The variation of pesticide residues in fruits and vegetables and the associated assessment of risk. Regul.Toxicol Pharmacol 1999;30(2 Pt 2):S34-S41. He X, Liu RH. Phytochemicals of apple peels: isolation, structure elucidation, and their antiproliferative and antioxidant activities. J Agric Food Chem. 2008 Nov 12;56(21):9905-10.

Hirahashi T, Matsumoto M, Hazeki K, Saeki Y, Ui M, Seya T. Activation of the human innate immune system by Spirulina: augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol. 2002 Mar;2(4):423-34. Kalafati M, Jamurtas AZ, Nikolaidis MG, Paschalis V, Theodorou AA, Sakellariou GK, Koutedakis Y, Kouretas D. Ergogenic and antioxidant effects of spirulina supplementation in humans. Med Sci Sports Exerc. 2010 Jan;42(1):142-51. Knopp RH, Superko HR, Davidson M, Insull W, Dujovne CA, Kwiterovich PO, Zavoral JH, Graham K, O’Connor RR, Edelman DA. Long-term blood cholesterol-lowering effects of a dietary fiber supplement. Am J Prev Med. 1999 Jul;17(1):18-23. Latté KP, Appel KE, Lampen A. Health benefits and possible risks of broccoli - an overview. Food Chem Toxicol. 2011 Dec;49(12):3287-309.

Angwafor F III, Anderson ML. An open5:1=580mg) label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J Licorice root extract (10% glycyrrhizin (Glycyrrhiza 116mg Mao TK, Van de Water J, Gershwin ME. Effects of a Spirulina-based dietary supplement on cytokine production from Int Soc Sports Nutr 2008;5:12. uralensis) allergic rhinitis patients. J Med Food. 2005 Spring;8(1):27-30. Brzeziska-Wcisło L. Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects treatment women. Wiad M, Nielsen CH, Balachandran P, Christensen O, Pugh ND,for Tamta H, SufkaofKJ,diffuse Wu X, alopecia Walsted A,inSchjørring-Thyssen

Acerola juice extract (18% vitamin C) (Malpighia punicifolia) Lek berry 2001;54:11-8.

115mg

Enevold C, Pasco DS. Enhancement of natural killer cell activity in healthy subjects by Immulina®, a Spirulina extract

enriched for Braun-type lipoproteins. Planta Med. 2010 acid Nov;76(16):1802-8. Siberian ginseng extract (0.8% eleutherosides 28:1=1680mg) 60mg using Chittur S, Parrroot B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes a composition containing carnitine, thioctic and saw palmetto extract. Evid Based Complement Alternat Med 2009. (Eleutherococcus senticosus) Oude Griep LM, Monique Verschuren WM, Kromhout D et al. Colours of fruit and vegetables and 10-year incidence of CHD. Br J Nutr. 2011 Jun 8:1-8. [Epub ahead of print]. 2011.

A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97. MilkPan thistle seed extract (86% silymarin 15:1=900mg) (Silybum 60mg Pouteau E, Ferchaud-Roucher V, Zair Y, Paintin M, Enslen M, Auriou N, Macé K, Godin JP, Ballèvre O, Krempf M. marianum) Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the fasting effectiveness of botanically derived inhibitors of 5-alpha-reductase in the Acetogenic fibers reduce glucose turnover but not peripheral insulin resistance in metabolic syndrome patients. Clin treatment of androgenetic alopecia. J Altern Complement Med 2002;8:143-52.

Organic Atlantic dulse seaweed (Palmaria palmata)

33mg

Ginkgo biloba leaf extract (24% ginkgo flavonglycosides, 6% terpene Sinclair R. Male pattern androgenetic alopecia. BMJ 1998;317:865-9. lactones 50:1=1000mg)

20mg

Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9.

Nutr. 2010 Dec;29(6):801-7. Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol. 2009Mar;130(3):244-51.

Riso P, Martini D, Møller P, Loft S, Bonacina G, Moro M, Porrini M. DNA damage and repair activity after broccoli intake Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human Plant FoodsMutagenesis. Hum Nutr2010 1999;53:359-65. in subjects. young healthy smokers. Nov;25(6):595-602.

Japanese green tea leaf (90% polyphenols, 20:1=300mg) (Camellia 15mg Riso P, Martini Martinetti A,and Porrini M. Effectlevels of broccoli intake markers related to oxidative stress and Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on D, bileVisioli acidF,absorption cholesterol in rats, Bron J Nutr 1993;69:277-87. sinensis) cancer risk in healthy smokers and nonsmokers. Nutr Cancer. 2009;61(2):232-7.

Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ European bilberry extract (25% anthocyanidins 100:1=1000mg) 10mg Rao AV. University of Toronto, Department of Nutritional Sciences. TEAC analysis of greens+ with and without lecithin. dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4. Personal communication to Genuine Health Inc, Sept 2010. (Vaccinium myrtillus L)

Grape skin and seed extract (95% proanthocyanidins, 200ppm Resveratrol (500:1=2500mg) (Vitis vinifera)

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5mg

Vuksan, V., Whitham, D., Sievenpiper, J. L., Jenkins, A. L., Rogovik, A. L., Bazinet, R. P., Vidgen, E., and Hanna, A. Supplementation of conventional therapy with the novel grain Salba (Salvia hispanica L.) improves major and emerging cardiovascular risk factors in type 2 diabetes: results of a randomized controlled trial. Diabetes Care 2007;30(11):2804-2810

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Calcium d-Glucarate SAP PRODUCT MONOGRAPH

BIOCHEMISTRY

In the body, calcium d‑glucarate is converted through a series of reactions to the active molecule d‑glucaro‑1,4‑lactone, which inhibits beta‑glucuronidase.(1, 2) d‑Glucaro‑1,4‑lactone has been found to be formed from d‑glucarate salt in the stomach. It is absorbed from the intestinal tract and transported via the bloodstream to internal organs.(2, 3) It is mainly excreted via urine, but also to a smaller extent in bile. (2) Calcium d‑glucarate works to enhance detoxification by increasing glucuronidation, and therefore enhancing excretion of potentially toxic compounds. Glucuronidation occurs during the second phase of liver detoxification, and is the process of taking hormones, carcinogens or other lipid‑soluble toxins and conjugating them with glucuronic acid for them to be excreted via the biliary tract.(1) β‑Glucuronidase can deconjugate these toxins, making it possible for the toxins to be reabsorbed into the body.(1) d‑Glucaro‑1,4‑lactone is able to inhibit the functioning of β‑glucuronidase, which results in an increase in excretion of the conjugated compounds and decreases the potential harm they could cause in the body.(1) Calcium d‑glucarate has the ability to reduce the β‑glucuronidase activity of intestinal bacteria, which enhances enterohepatic circulation; this results in a reduction of cholesterol synthesis, and decreased serum cholesterol levels.(1)

CALCIUM d‑GLUCARATE AND CANCER

Elevated activity of β‑glucuronidase is associated with an increase in risk for several different cancer lines, but in particular hormone‑dependent cancers like breast and prostate.(2, 3) Calcium d‑glucarate is a precursor for d‑glucaro‑1,4‑lactone, which increases the processing of carcinogens as well as other tumor promoters, by inhibiting β‑glucuronidase.(2, 4) d‑Glucaro‑1,4‑lactone and its precursors alter steroidogenesis, which changes the hormonal environment and proliferative status of the target organs, which is one of the mechanisms that they work to exert their anticancer action.(2) d‑Glucarate has the ability to suppress cell proliferation and inflammation, and can also induce apoptosis.(2, 4) In an animal model, researchers found that calcium d‑glucarate was able to inhibit carcinogenesis during the initiation and promotion phases, by inhibiting protein tyrosine kinase‑C activity and inducing transformation growth factor beta.(5) Supplementing the body with d‑glucarates improves the natural defense system of the body for eliminating tumor promoters and carcinogens.(2)

CALCIUM d‑GLUCARATE AND OXIDATIVE STRESS

A study examined the role of d‑glucaro‑1,4‑lactone, sodium d‑gluconate and calcium d‑glucarate on blood platelets that were under oxidative stress.(6) It is known that platelet activation is essential in tumor progression, inflammation, allergic reactions and haemostasis.(6) The study measured in vitro levels of specific oxidative stress markers including For more information visit: www.nfh.ca

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superoxide anion, carbonyl groups, 3‑nitrotyrosine protein, thiobarbituric acid reactive substances, and low molecular weight thiols.(6) Each of the substances tested significantly inhibited thrombin‑induced arachidonic peroxidation as well as platelet protein oxidation/nitration induced by peroxynitrite—a strong oxidant formed intravascularly in vivo.(6) In the presence of the glucose derivative, there was a significant decrease seen in nitrotyrosine formation, thiol oxidation and carbonyl group generation.(6) These results indicate that gluconate salts may be helpful, via antioxidant mechanisms, in preventing excessive platelet activation.(6)

CALCIUM d‑GLUCARATE AND FIBROCYSTIC BREAST DISEASE

Researchers examined fluid removed from cysts from women with fibrocystic breast disease (FBD) and compared the fluid with that of a control group of women who did not have benign breast disease. Results demonstrated that in selected cyst fluids, the level of β‑glucuronidase significantly influenced the ratio of unconjugated to glucuronidated estradiol.(7) Patients with fibrocystic breast disease fell into one of two distinct subpopulations, based on their level of β‑glucuronidase activity. One group had close to normal activity; however, the second group had an average serum β‑glucuronidase activity that was three times higher than the healthy controls.(7) This is an area that requires further research to determine what the cause of this variation is in the subgroups of women with FBD, but it does appear that elevated β‑glucuronidase activity may contribute to fibrocystic breast disease in some women.

SAFETY OF CALCIUM d‑GLUCARATE

No side effects have been reported with calcium d‑glucarate. Many pharmaceuticals, especially hormones, are metabolized in the liver by binding to glucuronic acid. It is therefore possible that taking calcium d‑glucarate may increase the elimination of certain pharmaceuticals and hormones from the body.

REFERENCES 1. 2. 3. 4. 5. 6. 7.

[No authors listed]. “Monograph: Calcium d‑glucarate”. Alternative Medicine Review 7, No. 4 (2002): 336–339. Zółtaszek, R., et al. “The biological role of d‑glucaric acid and its derivatives: potential use in medicine”. Postȩpy Higieny i Medycyny Doświadczalnej (online) 62 (2008): 451–462. Walaszek, Z., et al. “Metabolism, uptake, and excretion of a d‑glucaric acid salt and its potential use in cancer prevention”. Cancer Detection and Prevention 21, No. 2 (1997): 178–190. Heerdt, A.S., C.W. Young, and P.I. Borgen. “Calcium glucarate as a chemopreventive agent in breast cancer”. Israel Journal of Medical Sciences 31 (1995): 101–105. Webb, T.E., et al. “Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate: retinoid combination”. Anticancer Research 13 (1993): 2095–2100. Saluk-Juszczak, J. “A comparative study of antioxidative activity of calcium d‑glucarate, sodium d‑gluconate and d‑glucono‑1,4‑lactone in a human blood platelet model”. Platelets 21, No. 8 (2010): 632–640. Minton, J.P., et al. “β-Glucuronidase levels in patients with fibrocystic breast disease”. Breast Cancer Research and Treatment 8, No. 3 (1986): 217–222. © NFH Nutritional Fundamentals for Health 2012

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Calcium d-Glucarate SAP Science-based calcium d-glucarate for optimal detoxification

Calcium d-glucarate is a calcium salt of d-glucaric acid, which is a naturally occurring substance. Glucaric acid is found in several fruits and vegetables, with its highest concentration being found in cruciferous vegetables, apples, oranges and grapefruits, and it is also made in small amounts in the human body.(1) d-Glucarate is an important substance that assists the body in its quest to detoxify and eliminate various toxins, hormones and carcinogens from the system. Two of the mechanisms that the body uses to detoxify are conjugation and glucuronidation, by which the body binds water-soluble substances to hormones or carcinogens, making it easier for them to be excreted. The enzyme β-glucuronidase breaks the bonds formed during the detoxification process, which allows substances to recirculate in the body instead of being excreted. d-Glucarate inhibits β-glucuronidase, therefore encouraging the elimination of the potentially harmful toxins, carcinogens or hormones.

Each capsule contains:

ACTIVE INGREDIENTS

Calcium d-glucarate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 650 mg Contains no: Preservatives, artificial flavor or color, sugar, dairy, starch, wheat, gluten, corn, soy or yeast. Calcium d‑Glucarate SAP contains 60 capsules per bottle.

DOSAGE

Adults: Take 1–4 capsules daily or as directed by your health care practitioner.

INDICATIONS ɶ Calcium d‑Glucarate SAP can be used to enhance phase II detoxification by the liver. ɶ Calcium d‑Glucarate SAP may help prevent various types of cancers including breast, colon and liver cancers. ɶ Calcium d‑Glucarate SAP helps reduce serum cholesterol levels. ɶ Calcium d‑Glucarate SAP can help prevent platelet aggregation via its antioxidant mechanism. ɶ Calcium d‑Glucarate SAP may be a useful therapy for women with fibrocystic breast disease.

SAFETY

Calcium d‑Glucarate SAP may increase the excretion of some medications and hormones. If you are taking any medications regularly, speak with your health care practitioner before using this product.

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on finished product to ensure Calcium d‑Glucarate SAP is free of heavy metals, pesticides, volatile organics, PCBs and other impurities.

Scientific Advisory Panel (SAP): adding nutraceutical research to achieve optimum health

Nutritional Fundamentals for Health • 3405 F.-X.-Tessier, Vaudreuil, QC J7V 5V5 • Tel. 1 866 510 3123 • Fax. 1 866 510 3130 • www.nfh.ca

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Good news for fine print-reading, organic-loving, food-sensitive, vegan-friendly, wellness-seeking human beings. Introducing greens+O. From the makers of the original and best- selling Green Food in Canada, greens+O is for those who are both passionate and sensitive about the foods they eat. greens+O is dairy-free, gluten-free, soy-free and wheat-free. Itâ&#x20AC;&#x2122;s a vegan-friendly, nonGMO formulation made with 80%* certified organic ingredients. Available in Original or delicious açai & mango flavour. Welcome to the next evolution of greens+.

For greens+ clinical studies including energy, ORAC and PRAL go to http://bit.ly/J58rhb

genuinehealth.com *Original Flavour is 80% organic

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IHP October 2012