B2B Nutramedic&Cosmetics No.1

B2B

Nutramedic &Cosmetics No. 1 / NOVEMBER 2022

Lutein / Iron / Boswellia seratta Folat and folic acid / Natural hydroxytyrosol Probiotics in cosmetics / Probiotics lysates Natural texture modifiers

Nutramedic &Cosmetics

Editor's word

Contents 4

The role of food supplements in preserving eye health

Dear business partners, colleagues and friends, We are pleased to present the first issue of the free digital magazine B2B Nutramedic&Cosmetics, intended for ma­ nu­facturers of food supplements, medicines, cosmetics and medical products, manufacturers of active substan­ ces and other raw materials, packaging and machines, and all interested healthcare professionals.

We started the project with the desire to make the neces­ sary information and contacts available to companies and individuals in the region, and beyond, and thus contribute to B2B networking.

We are sending you the first issue of the new magazine, with the hope that it will start a whole series of new ac­ quaintances, collaborations, projects and new products.

It is up to you to choose the edition in Croatian or English.

We wish you lots of inspiration and creativity.

Concept for your new product

7

Global omega-3 market figures

8

FloraGLO® Lutein an important nutrient for mum and baby

Daria Šurić

M.Pharm.

B2B

Nutramedic &Cosmetics

Bimonthly digital magazine for industry professionals in health, nutrition and cosmetics sector Ingredients and raw materials / Contract manufacturing Equipment & Packaging / Services / Industry events www.nmc-magazine.com info@nmc-magazine.com Publisher: Darmell d.o.o.

Cvjetna cesta 11, 10000 Zagreb, Hrvatska Mob: + 385 91 68 12 444 darmell@protonmail.com www.dar-mell.com Supported by

www.inpharma.hr

The publisher does not assume responsibility for the opinions and data that the authors present in the magazine, as well as for the data and materials provided by companies for publication in texts and advertisements. It is not allowed to download any part of the content without the prior consent of the publisher.

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Folate Over Folic Acid for Healthy Pregnancies

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Unlimited possibilities of application of natural hydroxytyrosol

Nutramedic &Cosmetics

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New confirmation of Non-GMO status for BGG World

Boswellia serrata beneficial effects on health and potential challenges

Bioline - reliable partner for your projects

Curtis Health Caps contract development and manufacturing services for pharmaceutical projects

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His Majesty – Iron

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Impact of nutrients and dietary supplements on cognitive function

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Systematic review: Prebiotic effect evidenced for chicory root fibres

Medical plants photo herbarium: Chicory

Unique textures via natural-derived modifiers

Probiotics in cosmetics: probiotic skin care

Vita Nova - professional services offering raw materials and application Pycnogenol® and ADHD Confirmation of effectiveness without harmful side effects

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Probiotics lysates in skin care

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Let’s meet in Paris!

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Biofach Congress 2023 3

Nutramedic &Cosmetics

The role of food supplements in preserving eye health Addiction to digital devices, harmful solar radiation, long stays in enclosed and airconditioned spaces and degenerative changes caused by aging are contributing to the increasing consumption of dietary supplements aimed at eye health. In most of these supplements, lutein and zeaxanthin are most prevalent.

AUTHOR:

Daria Šurić, M.Pharm.

4

Age-related macular degeneration

Lutein and zeaxanthin are the only carotenoids that are deposited in the macula and in the eye lens.

In the scientific literature, it is confirmed that they have a positive effect on eye health, thanks to their antioxidant properties and the properties of filter­ ing harmful rays of the blue spectrum.

Human body cannot produce carotenoids on its own.

The Western diet on average provides 1.3-3 mg of lu­ tein and zeaxanthin per day. The reduced percentage of lutein and zeaxanthin in plasma has been proven to pose an increased risk of developing macular de­ generation and cataracts. Supplementation with 10 mg of lutein esters per day, showed an increase in the content of lutein in plasma and an increase in the density of macular pig­

ment, and therefore a decrease in the risk of develo­ ping macular degeneration and other eye diseases.

Nussbaum et al. In 1981, published an overview of historical facts on the topic of macular pigment and yellow spot, which was mentioned in literature as ear­ ly as 17821. Histological, biochemical and spectral stu­ dies have proven that the yellow color of the yellow spot comes precisely from lutein, a xantophilic pigment.

In 1994, Dr. Johanna Seddon and her collaborators from Harvard University, proved a link between lute­ in-rich food intake and a significant reduction in de­ generative changes in the eye of patients with ma­ cu­lar degeneration2. Accordingly, Seddon et al. con­ cluded that it is recommended to increase the inta­ ke of foods rich in lutein and zeaxanthin.

Furthermore, the results of a study involving 1,802

Nutramedic &Cosmetics female (Womens Health Initiative Study) showed that women with the highest concentrations of lutein and zeaxanthin in blood plasma showed a 32% lower chan­ ce of cataracts occurring3.

Richter and his collaborators conducted a doub­lemasked, placebo-controlled, randomized trial in which they investigated the impact of lutein supplementa­ tion on vision functions in people suffering from age­ related macular degeneration4. At the end of the stu­ dy, the density of macular pigment turned out to be higher in people who were given lutein or lutein with antioxidants. In 2010, Bernstein P. and collaborators published a review paper whose conclusion was that the density of macular pigment is an indicator of the amount of xantophiles in the eye, and that it may be a marker for predicting the risk for the formation of eye disease5.

In a study published in the Archives of Ophtalmo­ logy in 2011, Lintje Ho and collaborators showed that higher serum carotenoid levels, especially lycopene and zeaxanthin, were associated with a lower risk of macular degeneration.

Based on existing evidence, including from the well-­ known AREDS (Age Related Eye Disease Study) and AREDS2 studies, it can be concluded that the intro­ duction of antioxidants, especially lutein and zeaxa­n­ thin, is essential for patients diagnosed with macular degeneration to slow the progression of the disease.

At the end of the five-year AREDS2 study period, the researchers concluded that the new formulati­on could reduce the risk of progression of age-related macular degeneration by about 26%. After complet­ ing the five-year study period, the study partici­ pants were offered the final formulation of AREDS2, which included lutein and zeaxanthin instead of be­ ta-carotene (which was originally in the AREDS for­ mulation).

In a new June 2022 report from the AREDS2, 10 years of follow-up shows that the group of AMD pa­ tients who received the AREDS2 supplement with lu­ tein/zeaxanthin had no increased risk of lung cancer, with a 20% greater reduction in late AMD progre­s­si­ on in those assigned to the lutein/zeaxanthin supple­ ment compared those who received beta-carotene.

The results of this long-term epidemiological study, following the AREDS2 cohort, suggest that the com­ bination of lutein and zeaxanthin was an appropri­ ate substitute for beta-carotene, which in turn near­ ly doubled the risk of lung cancer. At the same time, there was no statistically significant increase in risk when taking lutein and zeaxanthin. Compared to be­ ta-carotene, lutein and zeaxanthin had a potentially beneficial association with late progression of age-­ related macular degeneration6.

It is important to mention that the status of caro­ tenoids in the mother during the gestation period can affect the development of macula in children, and pre­ natal supplementation may play a role in supporting the development of vision. It has been proven that the level of zeaxanthin in maternal serum correlates with the density of macular pigment in infants shortly af­ ter birth (Henriksen et al.)8. This indicates the key role of supplements for the nutritional status of mothers and the development of fetal macula in the womb.

Lutein and zeaxanthin can be ingested in food or dietary supplements. Lutein as an active substance first appeared on the market of food supplements in 1995, and today we can find it in hundreds of products.

One of the most famous manufacturers of lutein used as an active substance in dietary supplements is Kemin, whose lutein is known under the brand na­ me FloraGLO®. It is the most studied lutein on the mar­ket, with a scientifically proven effect in more than 100 clinical trials. It is of natural origin, with a re­putation for quality, safety and efficiency and it was the first lutein brand introduced to the global market. Over the past 25 years, it has sparked a "re­ volution" in the lutein market and provided the basis for the development and progress of the role of lu­ tein in preserving health. In studies it has been pro­ ven that FloraGLO® lutein increases the density of macular pigment and improves vision function7.

The increasing prevalence of glaucoma, macular degeneration, cataracts and other eye health prob­ lems is projected to drive the further growth of the global market of ingredients and dietary supple­ ments for eye health.

Glaucoma

Glaucoma is an optic neuropathy characterized by deterioration of the optic nerve and thinning of the retinal nerve fiber layer, most often associated with elevated intraocular pressure. This is one of the lead­ ing causes of irreversible blindness, if it is not detec­ ted and treated on time. The therapy that ophthal­ mologists use for primary open-angle glaucoma is to lower intraocular pressure using drugs, lasers or surgical therapy.

Neuroprotection represents a new chapter in the treatment of this disease, intended to preserve the structures and functions of the visual system. Seve­ ral molecules have neuroprotective properties, among which citicoline stands out. It's been tested in differ­ ent studies.

Citicoline is a nucleotide formed by ribose, cytosi­ ne, pyrophosphate and choline, which play a key role in the synthesis of phospholipids, especially gly­ce­ro­ ­phospholipid and phosphatidylcholine. Phospholipids are the main components of the cell membra­ne, which guarantee the structural integrity of cells and are a fundamental compound for several enzymes.

After oral administration, citicoline is hydrolyzed into choline and citidine in the intestinal wall, and then the latter is converted into uridine. After absorption, these compounds reach the central nervous system.

Citicoline has a neuroprotective effect through me­ chanisms relevant to glaucoma. The neuroprotecti­ ve effect of citicoline in open-angle glaucoma can be shown to be functional and morphological. The ef­ fects of oral citicoline are achieved at a dose of 5001,000 mg per day. Citicoline can be taken permanent­ How can we preserve healthy vision?

1

Healthy eating habits

2

Exercise regularly

3

Take regular breaks when looking at digital device screens (every 20 minutes)

4

Wear your sunglasses

5

Regular (once a year) examination of vision by a doctor

6

Avoid smoking

7

Dont forget to blink regularly

8

Get enough sleep

9

Adjust the brightness of digital device screens

5

Nutramedic &Cosmetics ly or in cycles. No side effects were reported during the study.

Citicoline can improve cognitive performance as well as the quality of life of patients with glaucoma.

The conclusion is that this relatively old nootropic drug, which is now on the market as a dietary sup­ plement, is a valuable addition to conventional treat­ ment and a rational option for open-angle glaucoma prophylaxis9,10.

Dry eye

According to the 1995 definition of the US Nation­ al Eye Institute, the dry eye is a disorder of the tear film due to lack of tears or excessive evaporation, which causes discomfort.

Dry eyes are one of the most common complaints of patients looking for eye care preparations. Dry eye problems are the result of a combination of featu­ res: prolonged use of digital devices, environmental conditions, and the use of contact lenses. More than 75% of consumers use artificial tears to treat dry eyes, and more than 60% agree that it is inconvenient to use eye drops, as the benefits are temporary.

Dietary supplements that help with dry eyes are just starting to develop, so far there are only a small number of them. However, the combination of some nutrients - lutein and zeaxanthin, vitamin D and ome­ ga-7 fatty acids - shows promising results in reliev­ ing the symptoms of a dry eye. Therefore, it is anti­ cipated that this segment of dietary supplements, together with the aforementioned segments of the market for food supplements for eye health, will al­ so grow more and more in the future.

References: 1

Nussbaum JJ, Pruett RC, Delori FC. Historic perspectives. Macular yellow pigment. The first 200 years. Retina. 1981;1(4):296-310.

PMID: 6758089.

2

Seddon JM, Ajani UA, Sperduto RD, et al., Dietary carotenoids, vitamins A, C, and E, and advanced age related macular degeneration. Eye Disease Case-Control Study Group, JAMA, 1994;272(18):1413–20.

3

Eye Disease Study (CAREDS): ancillary study of the Women’s Health Initiative, Arch Ophthalmol, 2006;124(8):1151–62.

4

Richer S, Stiles W, Statkute L, et al., Double-masked, placebo-con­ trolled, randomized trial of lutein and antioxidant supplementa­ tion in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial), Optometry, 2004;75(4):216–30.

5

Bernstein PS, Delori FC, Richer S, et al., The value of measurement of macular carotenoid pigment optical densities and distribu­ tions in age-related macular degeneration and other retinal disorders, Vision Res,2010;50:716–28.

6

Chew EY, Clemons TE, Agrón E, etal. Long-term Outcomes of Adding Lutein/Zeaxanthinand Ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. JAMA Ophthalmol. Published online June 02, 2022. doi:10.1001/jamaophthalmol.2022.1640

7

Roberts, Richard. “Methods of Treating Ocular Disorders.” Kemin Industries, Inc., assignee. Patent US9226940 B2. Jan. 2016. Kemin's patent covers three conditions for allages; presbyopia, hyperopia, andastigmatism

8

Henriksen BS, Chan GM. Importance of carotenoids in optimizing eye and brain development. Journal of pediatric gastroenterolo­ gy and nutrition. 2014;59:552.

9

Tian K., Shibata-Germanos S., Pahlitzsch M., Cordeiro M. F., (2015).

Current perspective of neuroprotection and glaucoma. Clin.

Ophthalmol. 9, 2109–2118. 10.2147/OPTH.S80445

10

Jünemann AGM, Grieb P, Rejdak R. Bedeutung von Citicolin bei der Glaukomerkrankung [The role of citicoline in glaucoma].

Ophthalmologe. 2021 May;118(5):439-448. German. doi: 10.1007/ s00347-021-01362-z. Epub 2021 Mar 17. PMID: 33730306; PMCID: PMC7967777.

6

Concept for your new product Products in the form of drops are usually used for dry eye disease. Offer a new concept to the market: a food supplement to alleviate the symptoms of dry eyes, with an ingredient whose effectiveness has been clinically confirmed.

Target group

Dry eyes disease is one of the most common superficial diseases of the eye. It has been noted that the prevalence of the dry eye occurs in the range of approxi­ mately 4.4% to as much as 50% among middle-aged and older people worldwide.

Today, it is estimated that almost 1.4 billion people worldwide suffer from dry eye syndrome.

Dry eyes are a growing consumer concern

Dry eyes is one of the most common complaints of patients seeking eye care.

Issues related to dry eyes are the result of a combination of features: prolonged digital device use, environmental conditions, genetics and use of contact lenses.

Why food supplement?

More than 75% of consumers use artificial tears to manage their dry eyes and more than 60% agree that it is inconvenient to use eye drops as the benefits are temporary.

Consumers seek a holistic solution to sooth their occasional dry eyes and more than 70% perceive supplements to be just as or more effective than their current therapy.

The concept of the new product

The ingredients of the product should have a proven effect - a clinical study.

The branded ingredient™ that we propose as an active substance has exactly that - clinically proven action on the regeneration of mucous membranes, and increases the eye mucos hydration by 18%.

If you want to learn more about the proposed branded ingredient, this concept or suggestions for another new products contact us.

Darmell d.o.o.

20+ years of experience in developing new concepts for food supplements

Mob: + 385 91 68 12 444 darmell@protonmail. com www.linkedin.com/ company/darmell/ www.dar-mell.com

Nutramedic &Cosmetics

Global omega-3 market figures GOED has released its annual report on the global market for EPA and DHA omega-3 fatty acids. The report includes data for 14 different omega-3 sources, 11 geographies, and 6 product types (dietary supplements, pharmaceuticals, infant formula, food and beverage, pet food and clinical nutrition).

T

he Global Organization for EPA and DHA Ome­ ga-3s (GOED) has published the 2022 edition of its annual Global EPA and DHA Omega-3 In­ gredient Market Report. The report details the en­ tire EPA and DHA omega-3 industry in the raw mate­ rials segment of the supply chain, which was a 115,031 metric ton (mT) market in 2021. Volume incre­ ased 2.1% last year, while the value of omega-3 in­ gredients increased 5.5%, to US$1.53 billion. As shown below, the industry is projected to reach 121,266 FIGURE 1

metric tons by 2024 to at an average annual growth rate of 1.8% globally. This year’s report includes mar­ ket figures for 14 omega-3 sources in 11 geographies and six end product applications (dietary supple­ ments, pharmaceuticals, infant formula, food and beverage, pet food and clinical nutrition). There are over 100 charts and tables detailing the volume and value of omega-3 sources, regions and end product applications in 2021, with forecasts through 2024.

New this year: To help companies navigate all the information provided, GOED has added “at a glance” charts to each section and created a set of Power­ Point slides with key market figures for companies to include in market presentations. The report also includes an Excel document with all the raw data as well as a forecast generator tool.

As a result of GOED’s intimate knowledge of the category and its access to proprietary sales data from member companies, the report is considered the most accurate and comprehensive report avail­ able on the global EPA and DHA industry.

A sample of the report, as well as purchase infor­ mation, is available at: www.goedomega3.com

GOED (Global Organization for EPA and DHA Omega-3s) represents the worldwide EPA and DHA omega-3 industry, with a mission to increase consumption of EPA and DHA omega-3s around the world. The membership is built on a quality standard unparalleled in the market and members must comply with quality and ethics guidelines that ensure members produce quality products that consumers can trust. Our 160+ members represent the entire supply chain of EPA and DHA omega-3s, from fisheries and crude oil suppliers to refiners, concentrators and fi­ nished product brands.

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Nutramedic &Cosmetics

FloraGLO Lutein ®

an important nutrient for mum and baby From its introduction to the market until today, FloraGLO Lutein has “revolutionized” the lutein supplementation market and provided the foundation for its development and application for human health. Its success is based on more than 100 peer-reviewed scientific articles published over the past 2 decades.

AUTHOR:

Samanta Maci, Kemin Human Nutrition and Health

F

loraGLO® Lutein is a free lutein ingredient sourced from tagetes erecta flowers and na­ tu­rally containing lutein, with an establi­shed reputation for quality, safety, and efficacy, and the first lutein brand introduced into the global market­ place. Since then, FloraGLO® Lutein revoluti­o­ni­zed the supplemental lutein market and provided the foundation for the development and advancement of lutein for human health. This advancement of lu­ tein science is evidenced by over 100 peer-reviewed scientific articles published over the past 2 decades, including the largest multi-center trial investigating the role of nutrition in supporting human vision, the second Age-Related Eye Disease Study (AREDS2)1. All this research establishes FloraGLO® Lutein as the most researched lutein brand worldwide.

Mechanism of action

Lutein (L) and its isomer zeaxanthin (Z) are non-­

8

provitamin A carotenoids commonly found in the hu­ man diet. Dietary rich sources of lutein and zeaxanthin are dark green leafy vegetables like spinach, brocco­ li and kale. Additionally, these carotenoids can also be found in egg yolk, corn and orange pepper.

Once in the body, lutein and zeaxanthin are found in all major organs as a result of their distribution via blood stream. Preferential deposition of dietary lu­ tein and zeaxanthin compared to other carotenoids has been found in the eye (where they compose the macular pigment), brain and breast milk2-4. The skin is also a good repository of lutein and zeaxanthin5.

The beneficial role of lutein and zeaxanthin for human health comes from one or more of the fol­ lowing established mechanisms of action: 1. absorption of short-wave blue light, 2. function as antioxidants, 3. reduction of inflammatory markers, 4. stabilization of membrane integrity6-9.

Nutramedic &Cosmetics These properties support the protective role of lu­ tein and zeaxanthin in light exposed organs such as eye and skin but also areas with high metabolic ac­ tivity, for example the brain.

FIGURE 1

Efficacy

Lutein has been shown important for visual and cog­ n­itive health at all stages of life. Emerging research has shown that these nutrients may be uniquely be­ neficial for developing infant eyes and brain. Concen­ trations of lutein and zeaxanthin have been report­ ed to increase during pregnancy while other carote­ noid levels remain fairly constant10. The same prefe­ rential increase in lutein and zeaxanthin levels over other carotenoids is also found in the cord blood11.

As lutein and zeaxanthin are transferred from mum to baby, they are deposited in specific areas to ad­ dress specific needs. As early as 17-22 weeks of de­ velopment, lutein and zeaxanthin are present in the developing fetus’ retina and lutein is the predominant carotenoid in the infant’s brain12,13. The presence of these nutrients in the eye and brain at early stages of life along with their higher concentration compa­ red to other carotenoids suggests that they may play a role in eye/brain development and/or protection.

Nature continues to provide lutein and zeaxanthin to the baby after birth. The colostrum, the first mum’s milk is rich in carotenoids which provide its charac­ teristic yellow color. Lutein and zeaxanthin are again preferentially secreted in breast milk and their lev­ els are proportional to their maternal intake4,14-16.

For what concerns eye development and health, lu­tein and zeaxanthin concentration in the macula of the eye increase during childhood and lutein is the dominant carotenoid in the infant retina. Prema­ ture babies have undetectable macular pigment. The changes in the lutein/zeaxanthin ratio in the macula appear to be closely related to steps in the anatomi­ cal and functional development12,17.

Observational studies indicate that serum lutein and zeaxanthin levels and macular pigment optical density (MPOD) are higher in infants fed with breast milk compared to infant formula and exposure to lu­ tein in infancy maybe related to higher MPOD in later life18,19. In the GUSTO study20 an observational study assessing the relationship between maternal lutein and zeaxanthin plasma concentrations during preg­ nancy and visual acuity (VA) in the offspring at 3 year of age in 471 mater-child pair, Liu et al. found that higher maternal lutein and zeaxanthin plasma con­ centrations during pregnancy were associated with lower likelihood of poor distance-VA in children. The authors concluded that maternal lutein and zeaxan­ thin status during pregnancy may influence the ba­ by early visual development.

The presence of lutein and zeaxanthin in the ma­ cu­la during the early stage of life is important consi­ dering that children are particularly susceptible to the potential damaging effects of excessive light ex­posure (solar light or artificial LED light) due to the immature eye development and the complete trans­ parency to light of the ocular lens (Figure 1)21.

Considering the possible beneficial role of lutein and zeaxanthin on brain development and overall health, lutein is the predominant carotenoid in the infant’s brain representing almost 60% of the brain carotenoids. Pre-term infants have significant lower

concentrations of lutein compared to term infants13.

The same lutein binding protein responsible for the accumulation of lutein in the retina is also present in the brain. and lutein concentration in the brain is hig­ hly correlated with the presence of this binding pro­ tein in the brain21.

A prospective study on 1580 mother-child pairs con­ cluded that higher gestational lutein intakes were associated with better child verbal intelligence and behavior regulation in mid-childhood23. High lutein and choline concentrations in breast milk have been found to be associated to better recognition memo­ ry in 6-month old infant. The author suggest that this cognitive advantage observed in infant ingesting mo­ re lutein could be associated with a more rapid de­ velopment of the visual system24.

Recently published papers from epidemiological stu­dies have indicated a positive association bet­we­ en MPOD, and cognitive performance including glo­ bal intelligence and executive processing, memory and academic achievement in school children25-27.

For what concerns intervention studies, FloraGLO® Lutein has 2 published studies on pregnancy and/or breastfeeding, 6 published studies on preterm in­ FIGURE 2

9

Nutramedic &Cosmetics 8

Kritchevsky SB, Bush AJ, Pahor M, Gross MD. Serum carotenoids and markers of inflammation in nonsmokers. Am J Epidemiol.

2000;152(11):1065–71.

9

Gruszecki WI, Strzałka K. Carotenoids as modulators of lipid membrane physical properties. Biochim Biophys Acta - Mol Basis Dis. 2005;1740(2):108–15.

10

Oostenbrug GS, Mensink RP, Al MDM, van Houwelingen AC, Hornstra G. Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation. Br J Nutr. 1998;80(1):67–73.

11

Thoene M, Anderson-Berry A, Van Ormer M, Furtado J, Soliman GA, Goldner W, et al. Quantification of lutein + zeaxanthin presence in human placenta and correlations with blood levels and maternal dietary intake. Nutrients. 2019;11(1):1–13.

12

Bone RA, Landrum JT, Fernandez L, Tarsis SL. Analysis of the macular pigment by HPLC: Retinal distribution and age study.

Investig Ophthalmol Vis Sci. 1988;29(6):843–9.

13

Vishwanathan R, Kuchan MJ, Sen S, Johnson EJ. Lutein is the predominant carotenoid in infant brain: Preterm infants have decreased concentrations of brain carotenoids. J Pediatr Gastroenterol Nutr. 2014;59(5):659–65.

14

Khachik F, Spangler CJ, Smith JC, Canfield LM, Steck A, Pfander H. Identification, Quantification, and Relative Concentrations of Carotenoids and Their Metabolites in Human Milk and Serum.

Anal Chem. 1997 May 15;69(10):1873–81.

15

Patton S, Canfield LM, Huston GE, Ferris AM, Jensen RG. Carotenoids of human colostrum. Lipids. 1990;25(3):159–65.

16

Cena H, Castellazzi AM, Pietri A, Roggi C, Turconi G. Lutein concentration in human milk during early lactation and its relationship with dietary lutein intake. Public Health Nutr.

2009;12(10):1878–84.

17

Bernstein PS, Sharifzadeh M, Liu A, Ermakov I, Nelson K, Sheng X, et al. Blue-light reflectance imaging of macular pigment in infants and children. Investig Ophthalmol Vis Sci. 2013;54(6):4034–40.

FloraGLO® Lutein established the benchmark of safety of supplemental lutein. The safety of FloraGLO was evaluated and confirmed by different authori­ ties around the globe including the Joint Food and Agricultural Organization (FAO) / World Health Orga­ nization (WHO) Expert Committee on Food Additives (JECFA), Food and Drug Administration with revision of various Generally Recognized As Safe (GRAS) dos­ siers and European Food Safety Authority (EFSA)39-41.

FloraGLO® Lutein can be successfully added to a wi­ de variety of dry and liquid galenic forms and to food and beverage applications. It is self-affirmed GRAS in and is the only lutein brand ingredient with a letter of non-objection from FDA for use in infant formulas41.

18

Neuringer M, Bone RA, Jeffrey B, Bettler J, Zimmer JP, Wallace P, et al. Lutein in Breastmilk and Infant Formula: Effects on Serum Lutein, Macular Pigment and Visual Function. Invest Ophthalmol Vis Sci [Internet]. 2009;50(13):1707. Available from: https://iovs. arvojournals.org/article.aspx?articleid=2364128

19

Liu Z, Meyers KJ, Johnson EJ, Snodderly M, Tinker L, Wallace R, et al. Exposure to Lutein in Infancy via Breast Milk and Later Life Macular Pigment Optical Density. Investig Ophthalmol Vis Sci [Internet]. 2015;56(7):192. Available from: http://iovs.arvojournals. org/article.aspx?articleid=2331661 http://ovidsp.ovid.com/ ovidweb.cgi?T=JS&PAGE=reference&D=emed16&NEWS=N& AN=615917349

20

Lai JS, Veetil VO, Lanca C, Lee BL, Godfrey KM, Gluckman PD, et al.

Maternal lutein and zeaxanthin concentrations in relation to offspring visual acuity at 3 years of age: The GUSTO study.

Nutrients. 2020;12(2):1–11.

21

Hammond BR. Possible role for dietary lutein and zeaxanthin in visual development. Nutr Rev. 2008;66(12):695–702.

References:

22

Tanprasertsuk J, Li B, Bernstein PS, Vishwanathan R, Johnson MA, Poon L, et al. Relationship between concentrations of lutein and stard3 among pediatric and geriatric human brain tissue. PLoS One. 2016;11(5):1–11.

23

Mahmassani H, Switkowski K, Scott T, Johnson E, RIfas-Shiman SL., Oken E, Jacques P. Maternal intake of lutein and zeaxanthin during pregnancy is positively associated with offspring verbal intelligence and behavior regulation in mid-childhood in the project Viva Cohort. J. Nutr. 2021 Mar11:151(3):615-627.

24

Cheatham CL, Sheppard KW. Synergistic effects of human milk nutrients in the support of infant recognition memory: An observational study. Nutrients. 2015;7(11):9079–95.

25

Barnett SM, Khan NA, Walk AM, Raine LB, Moulton C, Cohen NJ, et al. Macular pigment optical density is positively associated with academic performance among preadolescent children. Nutr Neurosci. 2018;21(9):632–40.

26

Walk AM, Khan NA, Barnett SM, Raine LB, Kramer AF, Cohen NJ, et al. From neuro-pigments to neural efficiency: The relationship between retinal carotenoids and behavioral and neuroelectric indices of cognitive control in childhood. Int J Psychophysiol.

2017;118(May):1–8.

27

Hassevoort KM, Khazoum SE, Walker JA, Barnett SM, Raine LB, Hammond BR, et al. Macular Carotenoids, Aerobic Fitness, and Central Adiposity Are Associated Differentially with Hippocam­ pal-Dependent Relational Memory in Preadolescent Children. J Pediatr. 2017;183(February):108-114.e1.

fants and 7 on term infants. In a intervention study conducted on lactating woman, daily supplementa­ tion for 6 weeks with FloraGLO® Lutein at 6 or 12 mg dose increased mother serum and breast milk levels of lutein which resulted in increasing lutein levels in the infant plasma (Figure 2). The study demonstra­ ted that lactating woman are highly responsive to lu­ tein supplementation which affects also the plasma concentrations in the newborn4. Studies conducted in healthy infants have shown that the administra­ tion of lutein (either through lutein fortified infant formula or separately added to the infant milk) was well tolerated, resulted in increase in plasma lutein levels and provided benefits in terms of reduction of oxidative stress28-32. The tolerability and absorp­ tion of FloraGLO® Lutein has been also confirmed in studies conducted in pre-term infants33-36. New rese­ arch has also addressed the benefit of FloraGLO® Lu­­tein supplementation on cognitive performance in children37.

Lutein and zeaxanthin cannot be synthesized de no­vo in the body and must be acquired through di­ etary sources, therefore it is very important to en­ sure an adequate intake of these carotenoids by the pregnant and breastfeeding mother and then during childhood. Data from USA indicate that the intake of L and Z is only 2 mg/day in women of childbearing potential38.

Safety and applications

1

Kemin. PubMed Search, summarized in KHTL-017-083.

2

Bernstein PS, Khachik F, Carvalho LS, Muir GJ, Zhao DY, Katz NB. Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye. Exp Eye Res. 2001;72(3):215–23.

3

10

Johnson EJ, Vishwanathan R, Johnson MA, Hausman DB, Davey A, Scott TM, et al. Relationship between serum and brain carotenoids, α -tocopherol, and retinol concentrations and cognitive performance in the oldest old from the georgia centenarian study. J Aging Res. 2013;2013(Mci).

4

Sherry CL, Oliver JS, Renzi LM, Marriage BJ. Lutein Supplementa­ tion Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids. J Nutr. 2014;144(8):1256–63.

5

Hata TR, Scholz TA, Ermakov I V., McClane RW, Khachik F, Gellermann W, et al. Non-invasive Raman spectroscopic detection of carotenoids in human skin. J Invest Dermatol.

2000;115(3):441–8.

6

Wooten BR, Hammond BR. Macular pigment: Influences on visual acuity and visibility. Prog Retin Eye Res. 2002;21(2):225–40.

7

Krinsky NI, Landrum JT, Bone RA. Biologic mechanism of the protective role of Lutein and Zeaxanthin in the Eye. Annu Rev Nutr. 2003;23:171–201.

Nutramedic &Cosmetics 28

Capeding R, Gepanayao CP, Calimon N, Lebumfacil J, Davis AM, Stouffer N, et al. Lutein-fortified infant formula fed to healthy term infants: Evaluation of growth effects and safety. Nutr J. 2010;9(1):1–9.

29

Mackey AD, Albrecht D, Oliver J, Williams T, Long AC, Price PT. Plasma carotenoid concentrations of infants are increased by feeding a milk-based infant formula supplemented with carotenoids. J Sci Food Agric. 2013;93(8):1945–52.

30

31

32

Bettler J, Zimmer JP, Neuringer M, Derusso PA. Serum lutein concentrations in healthy term infants fed human milk or infant formula with lutein. Eur J Nutr. 2010;49(1):45–51.

Perrone S, Longini M, Marzocchi B, Picardi A, Bellieni C V., Proietti F, et al. Effects of Lutein on Oxidative Stress in the Term Newborn: A Pilot Study. Neonatology [Internet]. 2010;97(1):36–40.

Available from: https://www.karger.com/Article/FullText/227291 Perrone S, Tei M, Longini M, Santacroce A, Turrisi G, Proietti F, et al. Lipid and protein oxidation in newborn infants after lutein administration. Oxid Med Cell Longev. 2014;2014.

33

Costa S, Giannantonio C, Romagnoli C, Vento G, Gervasoni J, Persichilli S, et al. Effects of lutein supplementation on biological antioxidant status in preterm infants: A randomized clinical trial.

J Matern Neonatal Med. 2013;26(13):1311–5.

34

Manzoni P, Guardione R, Bonetti P, Priolo C, Maestri A, Mansoldo C, et al. Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates in neonatal intensive care units: A multicenter randomized controlled trial. Am J Perinatol.

2013;30(1):25–32.

35

Rubin LP, Chan GM, Barrett-Reis BM, Fulton AB, Hansen RM, Ashmeade TL, et al. Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants. J Perinatol [Internet]. 2012;32(6):418–24.

Available from: http://dx.doi.org/10.1038/jp.2011.87

36

Romagnoli C, Tirone C, Persichilli S, Gervasoni J, Zuppi C, Barone G, et al. Lutein absorption in premature infants. Eur J Clin Nutr [Internet]. 2010;64(7):760–1. Available from: http://dx.doi. org/10.1038/ejcn.2010.62

37

Khan N. Brain Health and Kids: Lutein & Zeaxanthin’s Role in Cognitive Control and Academic Skills [Internet]. 2019. Available from: https://www.nutritionaloutlook.com/e-learning-tools/ brain-health-and-kids-lutein-zeaxanthins-role-cognitive-con­ trol-and-academic-skills

38

Johnson EJ, Maras JE, Rasmussen HM, Tucker KL. Intake of lutein and zeaxanthin differ with age, sex, and ethnicity. J Am Diet Assoc [Internet]. 2010;110(9):1357–62. Available from: http://dx.doi. org/10.1016/j.jada.2010.06.009

39

JECFA. Lutein from Tagetes erecta. Chemical and Technical Assessment [Internet]. 2004. Available from: http://www.fao.org/ fileadmin/templates/agns/pdf/jecfa/cta/63/Lutein.pdf%0A

40

Scientific Opinion of the Panel on Dietetic Products N and A. Safety, bioavailability and suitability of lutein for the particular nutritional use by infants and young children [Internet]. 2008.

Available from: https://www.efsa.europa.eu/fr/efsajournal/ pub/823

41

GRAS. U.S. Food & Drug Administration, 2004.GRAS Notice Inventory, GRN No. 140, 221 and 390.

Kemin Human Nutrition and Health samanta.maci@kemin.com www.kemin.com/health

11

Nutramedic &Cosmetics

Folate over folic acid for healthy pregnancies Folic acid supplementation is the standard of care for women seeking healthy pregnancies. However, new evidence identifies that active folate may be the more successful option for a wider population AUTHOR:

Lorena Carboni, Senior Scientific Communication Specialist, Product Manager at Gnosis by Lesaffre, Desio, Italy

F

olate is the generic term for vitamin B9. This water-soluble vitamin includes chemically si­mi­ lar compounds essential during rapid cell growth and division, critical for maintaining new cells and making DNA and RNA. Folate is recognized as one of the mandatory vitamin supplements during preg­ nancy and essential for many other conditions, like cardiovascular health, fertility, mood, and cognition.

Recent data suggest the need to distinguish bet­ ween naturally occurring folates and folic acid (FA), terms often mistaken and used interchangeably by practitioners and consumers, causing considerable confusion.1 In particular, 5-Methyltetrahydrofolate [methylfo­ late, 5-MTHF, or (6S)-5-MTHF], has been examined as a better alternative to folic acid supplementation2-5, especially for those expressing MTHFR polymorphism, which is approximately 40% of the global populati­on.6

Folate: sources and deficiency

People cannot synthesize folate, and due to its wa­ ter-soluble nature, the body stores folate to a limit­ ed extent. Therefore, folate must be obtained from the diet. Although naturally occurring folates are found in various foods, such as green leafy vege­tables, sprouts, fruits, brewer's yeast, and animal liver, it is exceedingly difficult for most people to get the daily recommended amount of folate through food alone.

Further, food folates are unstable and can be oxi­

dized (by heat, light, and/or metal ions), so cooking can reduce bioavailability.

While specific food processing procedures can mi­ nimize folate degradation, the absorption of folate is much more effective with fortified foods and sup­ plements (5-MTHF/folate and folic acid). In fact, in the last decades, the main form of folate supplementa­ tion has been represented by FA. Prescripti­ons of FA to women during the preconception period and preg­ nancy is a consolidated practice.8-11 The recommended dietary allowances (RDAs) for folate are 400 µg/day for adults and 600 µg/day for wo­men of childbearing age.12 Furthermore, many coun­ tries have initiated mandatory food fortification with FA to compensate for the losses and maintain ade­ quate dietary intakes.

Even still, folate deficiency is widespread and may occur when: dietary intake is inadequate; an incre­a­ sed need is not matched by increased intake (i.e., physiological conditions such as pregnancy, lacta­ tion, child growth, etc.); there is altered absorption/ excretion (or losses); or metabolism or drug use in­ terfere with the ability of the body to use folate.

Deficiency of folate may be asymptomatic or pre­ sent with symptoms of anemia, diarrhea, loss of ap­ petite, and weight loss. Additional signs are weak­ ness, sore tongue, headaches, heart palpitations, ir­ ritability, and behavioral disorders.7,13

Folate forms, metabolization, and polymorphisms

Folate includes a group of structurally related compounds: • Natural folates occur in foods, which also exist in many chemical forms, predominantly in the poly­ glutamate form; • Folic acid, the artificially synthesized form added in dietary supplements and fortified foods; • The biologically active form 5-methyltetrahydro­ folate (methylfolate) is also available in small amounts in foods and as a food ingredient.

While sometimes used interchangeably, folic acid and active folate are different. To become biologi­ cally active, folic acid must undergo several trans­ formation steps in the body.

This multi-step process converts biologically in­ active folic acid into the biologically active form of folate that our bodies use, called 5-methyltetrahy­ drofolate (5-MTHF). Specific enzymes control each

12

Nutramedic &Cosmetics step of this process. Some people, however, have a specific genetic trait (known as MTHFR polymor­ phism), which means they produce an unstable MTH­ FR enzyme with reduced activity, which is the final step in the conversion process. People with MTHFR polymorphism (approximately 40% of the global population6-7,14-15, therefore, have a lower ability to convert inactive forms of folate and folic acid into the biologically active 5-MTHF form.16,10,1 Because of this polymorphism, there is a signifi­ cant variation in how efficiently folic acid is convert­ ed to the bioactive form in different people, mean­ ing that even people who take folic acid can be defi­ cient in folate.

While it is ideal that we obtain our nutrients from food, the population cannot universally assume they can rely on the diet for food folates.

The limited conversion of FA may jeopardize fo­ late availability and increase the risk of adverse health outcomes. Cutting-edge scientific research sheds light on how much the MTHFR polymorphism is implicated in chronic disease states and how fo­ late nutrition may contribute to replacing adequate methylation and overall health. Supplementation with active folate 5-MTHF bypasses the entire folate metabolization, which is potentially impaired by MTHFR polymorphism. 5-MTHF is directly absorbed to exert biological activity. Therefore, using 5-MTHF as a food supplement instead of FA may be recom­ mended for external supplementation.10 While folic acid must be first converted into 5-MTHF, Quatrefolic®, (6S)-5-methyltetrahydrofola­ te glucosamine salt, is the biologically active form of folate that completely bypasses the potentially im­ paired MTHFR conversion step, negating the prob­ lem of people with polymorphisms in the folate-re­ lated enzyme and can better guarantee health bene­ fits. It passes the gastric barrier and is absorbed mainly in the small intestine by a carrier-mediated me­chanism. The carrier is not saturated, enabling (6S)-5-methyltetrahydrofolate glucosamine salt to ensure a higher folate uptake.17-18

Active folate and homocysteine in one-carbon metabolism

Regardless of how the active form of folate 5-MTHF has been obtained, the methylfolate, in con­ cert with vitamin B12, enters the one-carbon meta­ bolism, a network of interrelated biochemical reac­ tions that occurs in all cells of the body and is vital for various functions, including detoxification, ener­ gy production, immune function, maintaining and regulating genes, mood balancing, and controlling inflammation. It is essential for sustaining life and inhibiting or slowing the development of age-asso­ ciated diseases.

Perturbations of one-carbon metabolism, owing to low levels of 5-MTHF, critically contribute to in­ creasing circulating homocysteine levels and a toxic accumulation in the bloodstream.19 Prolonged exposure to high homocysteine (hy­ perhomocysteinemia – Hhcy) can damage the blood vessels, contribute to blood clots, and lead to the on­set of cardiovascular disease, including athero­ sclerosis, stroke, inflammatory syndromes, as well as neuronal pathologies. Because healthy blood ves­ sels and folate levels are essential for fertility and

FIGURE 1 Folate Intakes

pregnancy, high homocysteine can make it difficult to conceive and maintain a pregnancy. 20 Mazza et al. demonstrate the capacity of Quatre­ folic® at 400 µg (plus B6 and B12) to lower homocys­ teine serum levels better than conventional vitamin supplementation with highly dosed folic acid (5 mg/ day). Quatrefolic® was tested on hypertensive sub­ jects at low cardiovascular risk (104 patients with HCys ≥15 µmol/L). 21 The result shows significant HCys reduction com­ pared to the baseline from 21.5 µmol/L to 10.0 µmol/L. Moreover, the treatment was significantly effective, and the ideal HCys level was reached in 55.8% of ca­ ses in the Quatrefolic® group, and it was substantial­ ly higher than in the control. Polymorphisms in fo­ late pathway genes could be one reason for fertility complications in some women with unexplained in­ fertility. 21

Efficacy of 5-MTHF in pregnancy for averting birth defects

Adequate folate intake is particularly important for pregnant women, with a 5–10-fold higher requi­ rement than non-pregnant women. Folate supple­ mentation is required before and during pregnancy, with the indication to take folate 3 months before FIGURE 2 Folic Acid vs Folate metabolism

13

Nutramedic &Cosmetics conception and continue at least for the first 3 months of pregnancy. This is for protection from the risk of having a baby with Neural Tube Defects NTD, a malformation that develops in the first 28 days of pregnancy – before many women even know that they are pregnant.

Many studies have reported that Hhcy was associ­ ated with numerous pregnancy complications, inclu­ ding recurrent pregnancy loss22, neural tube defects23, preeclampsia24, preterm delivery25, placental abrup­ tion26,27, fetal growth restriction28, and gestational dia­ betes mellitus29. It was also observed that neonatal birth weight and maternal homocysteine levels were negatively correlated. 30 While the beneficial effects of folate supplementation in neural tube defect risk reduction have been clearly demonstrated31-33, more robust meta-analyses are needed to assess its effi­ cacy in preventing other congenital disabilities. 26,34-35 Interestingly, many studies have observed folate and homocysteine metabolism anomalies in children affected by Autism spectrum disorder (ASD). 36,37 Mo­ re importantly, folate supplementation during preg­ nancy may reduce the risk of delivering newborns affected by ASD38,19 and may improve children's lan­ guage competency. 39 But there is a clinically validated option: it has been shown that supplementing hypertensive subjects with 400 µg of Quatrefolic® (plus B6 and B12) for two months was more effective in reducing homocyste­ ine blood levels compared to folic acid. 21 Additional­ ly, supplementing pregnant women with Quatrefo­ lic® until the 24th week of pregnancy was more effi­ cient in increasing 5-MTHF blood levels than the sa­ me dose of folic acid.40 This study also confirms the importance of folate supplementation to avoid de­ veloping NTDs. In a recent retrospective study of 269 subjects, Ci­ rillo et al., investigated the role of vitamin B complex (Quatrefolic®, vitamin B12, vitamin B6 – Normocis® In­pha Duemila) supplement compared to only FA su­p­ plementation, in relation to clinical pregnancy and li­ ve birth in infertile women undergoing homologous ART (assisted reproductive technology). A higher per­ centage of women in the vitamin B complex supple­ mented group had a clinical pregnancy and live birth compared to the FA group. The authors concluded that women supplemented with Quatrefolic® and vi­ tamin B12 have a higher chance of clinical pregnan­ cy and live birth. Supplementation with vitamin B complex might be considered in clinical practice in women undergoing ART.41

Conclusion

While the standard of care for healthy pregnan­ cies has been the prescription of folic acid, recent data suggests this might not be an effective strate­ gy for all. Research dictates that the active form of folate provides a safe, effective solution for a broad­ er population, particularly those exhibiting MTHFR polymorphism, and should be a consideration for practitioners.

References:

14

1

Ulrich CM, Potter JD. Folate supplementation: too much of a good thing? Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):189-93.

2

Henderson AM, Aleliunas RE, Loh SP, Khor GL, Harvey-Leeson S, Gli­ er MB, et al. L-5-methyltetrahydrofolate supplementation incre­a­

ses blood folate concentrations to a greater extent than folic acid supplementation in Malaysian women. J Nutr. 2018;148:855–90.

3

Lamers Y, Prinz-langenohl R, Bramswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006;84:156–61.

4

Venn BJ, Green T, Moser R, Mann JI. Comparison of low-dose supplementation with L-5-methylterahydrofolate or folic acid on plasma homocysteine: a randomized placebo controlled study.

Am J Clin Nutr. 2003;77:658–62.

5

Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K. Supplementa­ tion with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr. 2004;79:473–8.

6

Wilcken B, Bamforth F, Li Z, et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): Findings from over 7000 newborns from 16 areas world wide. J Med Genet 2003;40(8): 619–25.

7

Ferrazzi, Enrico & Tiso, Giulia & Di Martino, Daniela. (2020). Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology. 253. 10.1016/j.ejogrb.2020.06.012.

8

Stover PJ. Folic acid. Folic acid. Modern Nutrition in Health and Disease. Lippincott Williams & Wilkins: Baltimore MD, 2012.

9

Singh J. Vitamin B9 in Dark Green Vegetables: Deficiency Disorders, Bio-Availability, and Fortification Issues. In: Guy LeBlanc J, ed. B-Complex Vitamins - Sources, Intakes and Novel Applications: IntechOpen, 2022.

10

Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahy­ drofolate are not the same thing. Xenobiotica 2014; 44:480–8.

11

Bailey LB, Gregory JF. Folate metabolism and requirements. J Nutr 1999; 129:779–82. L. B. Bailey and J. F. Gregory, “Folate metabolism and requirements,” The Journal of nutrition, vol. 129, no. 4, pp. 779– 782, 1999.

12

EFSA Scientific Opinion. Scientific Opinion on Dietary Reference Values for folate. EFSA Journal. 2014

13

Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, Molloy AM, Caudill MA, Shane B, Berry RJ, Bailey RL, Hausman DB, Raghavan R, Raiten DJ. Biomarkers of Nutrition for Development-Folate Review. J Nutr. 2015 Jul;145(7):1636S-1680S.

14

Maulik D, van Haandel L, Allsworth J, Chaisanguanthum KS, Yeast JD, Leeder JS. The effect of race and supplementation on maternal and umbilical cord plasma folates. J Matern Fetal Neonatal Med 2019:1–9.

15

Levin BL, Varga E. MTHFR: Addressing Genetic Counseling Dilem­ mas Using Evidence-Based Literature. J Genet Couns 2016; 25:901–11.

16

Patanwala I et al. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr. 2014 Aug;100(2):593-9.

17

Patanwala I et al. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr. 2014 Aug;100(2):593-9.

18

Pietrzik K et al. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodyna­mics.

Clin Pharmacokinet. 2010 Aug;49(8):535-48.

19

Tinelli C, Di Pino A, Ficulle E, et al., “Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathol­ ogies,” Frontiers in Nutrition, vol. 6, p. 49, 2019.

20

Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis 2011; 34:75–81.

21

Mazza A, Cicero AF, Ramazzina E, et al., “Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial,” Journal of biological regulators and homeostatic agents, vol. 30, no. 3, pp. 921–927, 2016.

22

Zhao X, Zhao Y, Ping Y et al., “Association between gene polymor­ phism of folate metabolism and recurrent spontaneous abortion in Asia,” Medicine, vol. 99, no. 40, e21962, 2020.

23

Yadav U, Kumar P, and Rai V. “Maternal biomarkers for early prediction of the neural tube defects pregnancies,” Birth Defects Research, vol. 113, no. 7, pp. 589–600, 2021.

24

Serrano NC, Quintero-Lesmes DC, Becerra-Bayona S, et al., “Association of pre-eclampsia risk with maternal levels of folate, homocysteine and vitamin B12 in Colombia: A case-control study,” PloS one, vol. 13, no. 12, e0208137, 2018.

25

Qiu X, F. Gao, Y. Qiu et al., “Association of maternal serum homocys­ teine concentration levels in late stage of pregnancy with pre­

Nutramedic &Cosmetics term births: a nested case–control study,” The Journal of Mater­ nal-Fetal & Neonatal Medicine, vol. 31, no. 20, pp. 2673–2677, 2018.

26

27

28

Dai C, Fei Y, Li J, et al., “A Novel Review of Homocysteine and Pregnancy Complications,” BioMed research international, vol.

2021, pp. 1–14, 2021.

Goddijn-Wessel TA, Wouters MG, Molen EFvd, et al. “Hyperhomo­ cysteinemia: a risk factor for placental abruption or infarction,” European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 66, no. 1, pp. 23–29, 1996.

Jiang HL, Cao LQ, and Chen HY, “Blood folic acid, vitamin B12, and homocysteine levels in pregnant women with fetal growth restriction,” Genetics and Molecular Research, vol. 15, no. 4, 2016.

36

Paşca SP, Nemeş B, Vlase L, et al., “High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism,” Life sciences, vol. 78, no. 19, pp. 2244–2248, 2006.

37

DeVilbiss EA, Gardner RM, Newschaffer CJ, et al., “Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence,” British Journal of Nutrition, vol. 114, no. 5, pp.

663–672, 2015.

38

Roth C, Magnus P, Schjølberg S, et al., “Folic Acid Supplements in Pregnancy and Severe Language Delay in Children,” JAMA, vol.

306, no. 14, p. 1566, 2011.

39

Li B, Zhang X, Peng X, et al., “Folic Acid and Risk of Preterm Birth: A Meta-Analysis,” Frontiers in Neuroscience, vol. 13, 2019.

29

Guven MA, Kilinc M, Batukan C, et al., “Elevated second trimester serum homocysteine levels in women with gestational diabetes mellitus,” Archives of Gynecology and Obstetrics, vol. 274, no. 6, pp. 333–337, 2006.

40

Dell'Edera D, Sarlo F, Allegretti A, et al., “Prevention of neural tube defects and maternal gestational diabetes through the inositol supplementation: preliminary results,” European Review for Medi­ cal and Pharmacological Sciences, vol. 21, no. 14, pp. 3305–3311, 2017.

30

Cawley S, O’Malley EG, Kennedy RAK, et al., “The relationship between maternal plasma homocysteine in early pregnancy and birth weight,” The Journal of Maternal-Fetal & Neonatal Medicine, vol. 33, no. 18, pp. 3045–3049, 2020.

41

Cirillo M, Fucci R, Rubini S, Coccia ME, Fatini C. 5-Methyltetrahydro­ folate and Vitamin B12 Supplementation Is Associated with Clini­ cal Pregnancy and Live Birth in Women Undergoing Assisted Re­ productive Technology. Int J Environ Res Public Health 2021; 18.

31

De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, et al., “Effects and safety of periconceptional oral folate supplementation for preventing birth defects,” The Cochrane database of systematic reviews, no. 12, CD007950, 2015.

32

Blom HJ, “Folic acid, methylation and neural tube closure in humans,” Birth defects research. Part A, Clinical and molecular teratology, vol. 85, no. 4, pp. 295–302, 2009.

33

Blencowe H, Cousens S, Modell B, et al., “Folic acid to reduce neonatal mortality from neural tube disorders,” International journal of epidemiology, 39 Suppl 1, i110-21, 2010.

34

Liu C, Liu C, Wang Q, et al., “Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis,” Archives of gynecology and obstetrics, vol. 298, no. 4, pp. 697–704, 2018.

35

Ali A, Waly MI, Al-Farsi YM, et al., “Hyperhomocysteinemia among Omani autistic children: a case-control study,” Acta Biochimica Polonica, vol. 58, no. 4, 2011.

Distributed by: Hermes Consilium Ltd. Cesta v Mestni log 88a 1000 Ljubljana, Slovenia T. +386 1 434 56 78 info@hermes-consilium.com www.hermes-consilium.com

Author bio With a Master's in Pharmaceutical Chemis­ try and Technology and 20+ years of experi­ ence in the nutraceutical and pharmaceuti­ cal industries, Lorena Carboni is specialized in clinical aspects of natural ingredients, with a particular focus on the One Carbon metabolites. A Scientific Communication Spe­cialist with Gnosis by Lesaffre, she has executed educational projects and publica­ tions, working closely with several universi­ ties and academic panels of experts.

15

Nutramedic &Cosmetics

Unlimited possibilities of application of natural hydroxytyrosol Hytolive® Infinity is an unique olive fruit extract rich in natural hydroxytyrosol that can be incorporated into any source of edible oils, including omega-3 (fish, krill, algae) and seeds oils (high oleic sunflower, grape seed, canola, soy, etc.).

AUTHOR:

Carlos Peña, CEO, GENOSA ID SL

16

O

live fruit extracts standardized in natural hy­ droxytyrosol are experiencing significant growth and more and more consumers are aware of the healthy advantages of this ingredient. In fact last 2011, the EFSA Panel of Experts issued a sci­ entific opinion concluding that a cause and effect re­ lationship could be established between the consum­p­ ­­tion of olive oil polyphenols (standardised by the con­ tent of hydroxytyrosol and its derivatives) and pro­ tection of LDL particles from oxidative damage. This led to their inclusion in the list of approved health claims (432/2012).

Genosa is the leading company in offering olive fruit extracts standardized in natural hydroxytyrosol.

Its extracts are being incorporated into dietary sup­ plements and functional foods worldwide.

So far these extracts could be added into water sol­ uble products. However, Genosa has given a step fur­ ther and made the possibility of incorporating them into vegetable oils.

Fats are necessary for our body, since they provide

not only essential fatty acids but also other nutrients or molecules that our body could not manufacture. In addition, they exert various vital functions, such as storing energy, serving as a structure to produce hor­ mones and other substances, and facilitating the tran­sport of various vitamins. Lipids form part of our cells.

The relationship between health and fat intake does not depend so much on its quantity, but on its quality, that is, the type of fatty acid predominant in the diet.

They are necessary for proper cell function, and they are an important source of energy together with glycogen, which is the fastest way for the body to ob­ tain the necessary strength to face activity and also a vehicle of other ingredients or biocomponents with biological effects, such as sterols, vitamins and phe­ nolic compounds.

In the last years the so called “functional oils” are being formulated in order to offer a global solution for the maintenance of an optimal health and the mi­ ti­gation of many risk factors.

Depending on the target, to reach the optimal

Nutramedic &Cosmetics combination of monounstaurated and polyunsatu­ rated fatty acids, proper omega-6/omega-3 ratio, the ideal amount of daily EPA and DHA, etc. is very rele­ vant and offer consumers a real solution for their dai­ ly specific needs.

Vitamin D, Vitamin E, Vitamin K2 MK-7, CoQ10 and many other actives are being included into such daily functional oils.

Genosa is the leading natural hydroxytyrosol actor (Hytolive®). Hydroxytyrosol is the main ortodiphenol in olives. Hytolive® is obtained from the water phase of olives. The ortodiphenol chemical structure and its low molecular weight makes it a molecule with a promising present and future.

Extra virgin olive oil contains olive polyphenols, mainly hydroxytyrosol and tyrosol derivatives (fat so­ luble) and in lower concentration, hydroxytyrosol and tyrosol (water soluble). According to a wide number of clinical studies, the presence of these polyphenols to­gether with a high percentage of oleic acid, make this oil one of the most promising combinations for heart health, among others.

Very recently clinical studies have shown the bene­ fits of high polyphenols extra virgin olive oil against low polyphenols virgin olive oil, proving the key role of olive polyphenols (hydroxytyrosol and tyrosol).

Genosa has developed a new technology to trans­ fer natural hydroxytyrosol and tyrosol (water soluble molecules) into oils. This technology does not include any additive, emulsifier or encapsulation.

“We have opened a new opportunity for all kinds of oils to incorporate natural hydroxytyrosol and tyrosol with no impact in visual aspect”. Any consumer world­ wide could ingest natural hydroxytyrosol and tyrosol through any fat source. This opens the possibility for many consumers worldwide to have access to these interesting compounds (the antioxidant essence of olives) through their daily diet”, Carlos Peña, Genosa CEO. Genosa has recently launched Hytolive® Infinity, a line of diverse oily extracts formulated with different kinds of oils (omegas, high oleic sunflower oil, canola, soya, …) including natural olive polyphenols.

Genosa was founded in 2001 and it is the worldwide innovator and pioneer company in the production and commercialization of natural hydroxytyrosol derived from the olive fruit. Its technology consists of a process using just physical and mechanical means and has been patented internationally. No solvents are used to extract the hydroxytyrosol.

GENOSA ID SL Parque Tecnológico de Andalucía C/ Iván Pavlov, 8, bajo G 29590 Campanillas MÁLAGA, Spain Phone: +34 952 02 85 80 info@genosa.com www.genosa.com www.youtube.com/watch?v=iZ3sEtYymlQ

New confirmation of Non-GMO status for BGG World ApplePhenon® and TheraPrimE® - two brands from the BGG World portfolio - have passed the rigorous procedure of the company Non-GMO Project and received a label confirming that they do not contain GMO ingredients.

N

on-GMO Project is a mission-driven nonprofit organization offering a third-party Non-GMO verification program to the standard consu­ mers expect. Non-GMO Project pioneered the market and established itself as leader for GMO avoidance.

BGG already was part of the Non-GMO Project with several offerings in their AstaZine® Natural Astaxan­ thin product line, but has now added ApplePhenon® and its full range of Tocotrienols (TheraPrimE®) to the NGPV certification as this designation has become sought after by many progressive brands in several key markets.

ApplePhenon® is a unique extract from mother ap­ples from the region of the earth where the apple spe­ cies originated. It possesses a unique and fully-­cha­ racterized phytochemical profile rich in absorbable and non-absorbable proanthocyanins. The non-­ab­sor­ bable proanthocyanins’ fraction of ApplePhenon® has been shown to improve the bioavailability of the ab­ sorbable fraction and, in addition, to work in the mo­ dulation of the gut microbiota by boosting the pro­ portion of Akkermansia. ApplePhenon® has pro­prie­tary clinical literature spanning 17 human cli­ni­cal stu­dies, and is supported by more than 50 publicati­ons that show potential for seven different health be­ne­fits.

Theraprime® is a premium line of Tocotrienol mix­ tures. Extracted from 3 distinctive sources (Annatto, Palm or Rice Bran Oil), each product possesses a uni­ que phytochemical profile and specific activity. Whi­ le the activity of α-tocopherol is well known, the bi­ ological role of Tocotrienols has been largely under­ estimated despite studies showing their unique phy­ siological functions. Recent research has suggested that Tocotrienols, the lesser-known congener of Vi­ tamin E, show antioxidant activities that are 40–60 times greater than those of tocopherols, and pos­ sess unique biological functions unrelated to anti­ oxidant activity, not sha­red by tocopherol and sup­ porting many potential health benefits demonstrat­ ed in over 600 medical research studies.

“We’re extremely pleased to have attained this re­ spected designation for more of our most important ingredients,” said Yanmei Li, PhD, BGG’s Global Chief Scientific Officer. “The need of transparency thro­ug­ hout the entire food chain is increasing, so we took this step to assure our customers that BGG’s products are completely natural and free from any genetic ma­ nipulation.”

More information: www.bggworld.com

17

Nutramedic &Cosmetics

Boswellia serrata beneficial effects on health and potential challenges

Indian frankincense tree offers various options in the creation of finished products.

Attention should be paid to the challenges of bioavailability and to more modern technological designs of the extract.

T AUTHOR:

Ana Gjergja Sekulić, Mag.Pharm, univ.mag. phytotherapy with dietotherapy

he Indian frankincense tree is an evergreen tree with a peeling bark. For therapeutic pur­ poses, oil re­sin is used, which is collected from the cut bark of the trunk or thicker branches. The resin comes out in the place of the incision and is so­ lidified by exposure to air. It can be collected fresh or dried all year round.1,2 The main ingredients of frankincense resin are monoterpenes (α-thujene) and diterpenes (macrocy­ clic diterpenoids such as incensole, incensole oxide, iso-incensole oxide, a diterpene alcohol [serratol]); tri­ terpenes (such as α- and β-amyrins); pentacyclic tri­ terpenic acids (boswellic acids) that are considered a carrier of action. 3 The representation of boswellic acid in oil resin is about 30%, and can be in α and β configuration. Various pharmacological studies ha­ ve shown that β configured derivatives have better activity than α isomers.4 Boswellia resin has been used for centuries in folk medicine for the treatment of various topical and sy­stemic inflammatory diseases. Recent experimen­ tal studies in animals and humans support folk medi­ cine indications and demonstrate the potential of frankincense resin in the treatment of inflammatory disorders such as inflammatory bowel disease, rheu­ matoid arthritis, osteoarthritis and asthma4, and even some types of cancer.5

Mechanism of action and pharmacokinetics

The pharmacological effects of frankincense, as already noted, are attributed to the boswellic acid, namely its two derivatives, 11-keto-β-boswellic acid

and acetyl-11-keto-β-boswellic acid, which were thought to express their action by selective inhibi­ tion of 5 LOX (5-lipooxygenase) inhibiting the pres­ ence of inflammatory leukotriene molecules. But this is not the only mechanism. Boswellic acid has been found to act on various molecular targets, in­ cluding enzymes, growth factors, kinases, transcrip­ tion factors and receptors.6,7 An overview of molecu­ lar targets can be seen in Figure 1.

Potential problems with the supplementation of bos­wellic acid are in its bioavailability. Given that 11-­­ke­to-β-boswellic acid (KBA) and acetyl-11-keto-­βboswellic acid (AKBA) are extremely lipophilic mole­ cules, they show reduced absorption through the gastrointestinal tract, and high retention time. Pre­ liminary pharmacokinetic studies have shown low concentrations of AKBA and KBA in plasma after ad­ ministration of boswellic acid. According to some re­ ports, it is the deacetylation of KBA8-11, while accor­ ding to others it is an extensive phase and metabo­ lism in liver microsomes and hepatocytes.12 Another important pharmacokinetic parameter is the elimi­ nation of molecules from the body. The study proved a half-time of boswellic acid elimination of about six hours, so it is concluded that oral administration is required every six hours. The study also reported that a stable state of the active substance would be achieved in plasma after about thirty hours.11 Given the potential of boswellic acid, work is being done to find new technological methods to increase the bio­ availability of the compounds. One of the promising methods is the preparation of extracts in solid lipid particles. The extract prepared in this way shows significantly better bioavailability.13 Some of the ot­ her methods are connecting to lecithin, binding it to liposomes, tying it to nanostructured lipid carriers, micelles, and poly nanoparticles.14-16

Possibilities of application of Indian frankincense in chronic diseases

Chronic inflammatory diseases around the world threaten the health and quality of life of many peo­ ple. They lead to functional limitations and signifi­ cantly affect the physical and psychological condi­ tion of the patient. They require continuous control and treatment over a long period of time, and in so­ me even throughout the lifetime. Although we have a number of medicines, they sometimes do not give

18

Nutramedic &Cosmetics satisfactory results or cause side effects that redu­ ce patients compliance. Also, the high cost of treat­ ment using certain drugs opens the possibility for the use of complementary therapies, for example, phytotherapy. That is why Indian frankincense has found its place in the therapy of chronic diseases.

Inflammatory bowel disease

Inflammatory bowel disease is a term that inclu­ des two diseases, Crohn's disease and ulcerative co­ litis. Both diseases are of unknown origin with a pro­ nounced genetic as well as environmental factor. They are characterized by bowel pain, diarrhea or consti­ pation, loss of appetite and weight loss, fatigue and generally reduced quality of life. They are marked by the alternation of the remission and relapse phases.17 A study on the effects of Indian fran­kincense extract in patients with ulcerative colitis, showed that apply­ ing the extract at a dose of 350 mg three times a day, for six weeks, improved stool properties, histopatho­ logy and blood parameters, in­cluding Hb, serum iron, calcium, phosphorus, prote­ins, total leukocytes and eosinophils. The effect was measurable with the ef­ fect of applying sulfasalazin at a dose of 1 g three ti­ mes a day. The percentage of remission was 82% in the Indian frankincense treatment group, while in the sulfasalazine group remission was 75%.18 The next six-week study by the same authors included a group that received Indian frankincense therapy at a dose of 900 mg three times a day, and a group treated with sulfasalazine at a dose of 3 grams three times a day.

70% of patients on incense therapy entered remis­ sion, while in the sulfa­salazine group, remission was observed in 40% of pa­tients.19 In a study that tracked the effect of Indian frank­ incense and mesalazine in Crohn's disease, Indian frankincense extract showed the same efficacy as the drug mesalazine. 20 Although both studies show very good results, it should be noted that these are nevertheless studies of an older date. In a more re­ cent review study by Abdel-Tawab and Wertz in 2011, a more detailed insight can be obtained on the ef­ fect of Indian frankincense extract on cytokines, li­ pooxygenase, and other molecular targets in inflam­ matory bowel diseases. 21

Rheumatoid arthritis and osteoarthritis

Rheumatoid arthritis is a chronic disease characte­ rized by swelling, soreness and stiffness of the jo­ints and loss of their function. The constant inflammato­ ry process affects the synovial fluid and gradually destroys collagen, reducing the space in the jo­ints, which ultimately destroys the bone itself. 22 Osteoarthritis is a chronic, progressive degenera­ tive disease of the joints that occurs with the decay of articular cartilage and the second most common ca­u­se of chronic incapacitation. 23 The effect of Indian frankincense extract and bos­wellic acid on the mediators of inflammation and symptoms of the disease has been studied by nu­ merous in vitro studies and animal studies. Boswell­ ic acid in vitro has shown an inhibiting effect on cy­ tokines such as TNF-α, IL-1β and pro-inflammatory enzymes (catG, 5-LO, p12LO, COX-1) in the range of concentrations between 0.6 and 55 mmol/L. The re­ sult of the use of Indian frankincense and boswellic

acid extract in animals with arthritis symptoms showed an effect on inhibition of edema, paw volume, de­ crease in the number of leukocytes in synovial fluid and generally inflammatory parameters. 21 Several clinical studies have also been conducted.

A randomized double-blind study over 8 weeks asses­ sed the effectiveness, safety and tolerability of Bos­ wellia serrata extract (BSE) in 30 patients with knee osteoarthritis. All patients in the group receiving in­ cense extract reported a decrease in knee pain, incre­ ased knee flexion and increased walking distan­ce. The frequency of the swelling in the knee joint is also re­ duced. Subjects tolerated well the use of extract. 24 Branded ingredient Boswellin® in dietary supple­ ments, an extract of Indian frankincense containing 3-acetyl-11-keto-β-boswellic acid and β-boswellic acid was tested by a double-blind study in 48 patients with osteoarthritis during 4 months. The results showed significantly improved patients physical function by reducing pain intensity and stiffness compared to placebo. The distance of the knee joint was im­ proved, osteophytes formation decreased as well as serum levels of the C-reactive protein. 25 The action of 5-Loxin, an extract of Indian frankin­ cense enriched with 30% 3-O-acetyl-11-keto-β-bos­ wellic acid, was also investigated. A double-blind ran­ domized study lasting three months assessed the effectiveness and safety of using 5-Loxin in the tre­at­ ment of knee osteoarthritis. 70 patients received therapy of 100 and 250 mg per day. Both doses of 5-Loxin yielded clinically and statistically significant improvements in pain intensity scores and physical function results. A significant improvement in the re­ sult of pain and functional ability was observed in the group receiving 250 mg of 5-Loxin already 7 days af­ ter the start of treatment. A significant decrease in metalloproteinase-3 matrix of synovial fluid was also observed. The extract showed a good safety profi­le.26 A pilot study was also carried out with a combined gastroresistent preparation of Indian frankincense and bromelain extract, which examined whether such a preparation could improve the quality of life of pa­ tients with osteoarthritis. Study included 49 pati­ents taking an Indian frankincense and bromelain-based FIGURE 1 The action of boswellic acid

Taken from: Int. J. Mol. Sci. 2019, 20(17), 4101; https://doi. org/10.3390/ijms20174101

19

Nutramedic &Cosmetics supplement over a period of one to six months. At the beginning and end of the study, patients completed a questionnaire for self-assessment of quality of life related to their independence in the performance of daily activities. In the follow-up period, after three months, a significant improvement was observed for seven out of ten questions from the initial quali­ ty of life questionnaire. The most significant impro­ vements were observed in the joints that were more severely affected at the beginning. No side effects or drug interactions were reported. 27

Other application options

Asthma - Although the Indian frankincense in folk me­ dicine was used for the purpose of treating asthma, there is not much research data on the action. Only one clinical trial has been conducted. With a six-week double-blind study, the effect of incense extract at a dose of 300 mg three times a day was examined. In the extract group, 70% of patients saw improve­ ments in lung function and immune function. 28 Cancer - High incidence and mortality due to cancer requires constant new research and finding new in­ gredients that would be effective in prevention and treatment. Various studies have shown the effecti­ve­ ness of boswellic acid in the prevention and treat­ ment of breast, bladder, cervical, prostate, colon, head and neck, liver, lungs and pancreatic cancers. It is im­ portant to point out that most of the studies carried out were done in vitro, and only a few on animal mod­ els. The examined effects of Indian frankincense ex­ tract and boswellic acid have shown action at differ­ ent molecular levels such as regulation of program­ med cell death, oncogene expression, expression of suppressor gene tumors, inducement of malignant cell apoptosis. 29 The potential for application cer­ tainly exists, but further research will show the real effectiveness of application in humans.

Given the available research, Indian frankincense is certainly an ingredient worth paying attention to.

As it shows a certain amount of challenges in bio­ availability, more attention needs to be paid in choosing the right type of extract, giving priority to modern technological designs.

References: Bown D. The Herb Society of America New Encyclopedia of Herbs and Their Uses. London, UK: Dorling Kindersley Limited; 2001.

2 Wichtl M (ed.), Brinckmann JA. Lindenmaier MP (trans.). Olibanum.

In: Herbal Drugs and Phytopharmaceuticals. A Handbook for Practice on a Scientific Basis. Stuttgart, Germany: Medpharm Scientific Publishers; 2004:418-420.

3 Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP. Boswellic acids: Novel, specific, non-redox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 1992;261:1143-6.

4 Poeckel D, Werz O. Boswellic acids: biological actions and molecular targets. Curr Med Chem 2006; 13: 3359-69 5 Takahashi M, Sung B, Shen Y, Hur K, Link A, Boland CR, Aggarwal BB, Goel A. Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family. Carcinogenesis 2012, 33, 2441–2449 6 Int. J. Mol. Sci. 2019, 20(17), 4101; https://doi.org/10.3390/ ijms20174101 pristupljeno 16.9.2022.

7 Roy N K, Deka A, Bordoloi D, Mishra S, Kumar AP, Sethi G, Kunnumakkara A B. The potential role of boswellic acids in cancer prevention and treatment. Cancer Lett. 2016, 377, 74–86.

8 Sterk V, Buchele B, Simmet T. Effect of food intake on the bioavailability of boswellic acids from a herbal preparation in healthy volunteers. Planta Med. 2004, 70, 1155–1160.

1

20

Tawab MA, Kaunzinger A, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M. Development of a high-performance liquid chromatographic method for the determination of 11-keto-beta-boswellic acid in human plasma. J. Chromatogr.

BBiomed. Sci. Appl. 2001, 761, 221–227.

10 Buchele B, Simmet T. Analysis of 12 different pentacyclic triterpe­ nic acids from frankincense in human plasma by high-perfor­ mance liquid chromatography and photodiode array detection. J. Chromatogr. B Anal.Technol. Biomed. Life Sci. 2003, 795, 355–362.

11 Sharma S,Thawani V, Hingorani L, Shrivastava M, Bhate V R, Khiyani R. Pharmacokinetic study of 11-Keto beta-Boswellic acid.

Phytomedicine 2004, 11, 255–260 12 Kruger P, Daneshfar R, Eckert G P, Klein J, Volmer D A, Bahr U, Mulle W E, Karas M, Schubert-Zsilavecz M, Abdel-Tawab M. Metabolism of boswellic acids in vitro and in vivo. Drug Metab.

Dispos. 2008, 36, 1135–1142.

13 Kulkarni PD, Damle ND, Hingorani L, Bhaskar VH, Ghante MR, Patil A, Gurjar M, Gota V. Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects. Drug Metab Pers Ther. 2021 Apr 5;36(3):215-221. doi: 10.1515/dmpt-2020-0176. PMID: 34412175.

14 Husch J, Bohnet J, Fricker G, Skarke C, Artaria C, Appendino G, Schubert-Zsilavecz M, Abdel-Tawab M. Enhanced absorption of boswellic acids by a lecithin delivery form Phytosome R of Boswellia extract. Fitoterapia 2013, 84, 89–98 15 Aqil F, Munagala R, Jeyabalan J, Vadhanam M V. Bioavailability of phytochemicals and its enhancement by drug delivery systems.

Cancer Lett. 2013, 334, 133–141.

16 Wang S, Su R, Nie S, Sun M, Zhang J, Wu D,Moustaid-Moussa N. Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. J. Nutr. Biochem. 2014, 25, 363–376 17 https://www.plivazdravlje.hr/bolest-clanak/bolest/60/ Upalna-bolest-crijeva.html, pristupljeno 19.9.2022.

18 Gupta I,Parihar A, Malhotra P, Singh G B, Ludtke R, Safayhi H, Ammon H P. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur. J. Med Res. 1997, 2, 37–43.

19 Gupta I, Parihar A, Malhotra P, Singh G B. Effects of Gum Resin of Boswellia serrata in Patients with Chronic Colitis. Planta Med 2001; 67(5): 391-395 20 Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R. Therapie des aktiven Morbus Crohn mit dem Boswellia-serrata-Extrakt H 15 [Therapy of active Crohn disease with Boswellia serrata extract H 15]. Z Gastroenterol. 2001 Jan;39(1):11-7. German. doi: 10.1055/s-2001-10708. PMID: 11215357.

21 Abdel-Tawab M, Wertz, O. Boswellia serrata An Overall Assessment of In Vitro, Preclinical, Pharmacokinetic and Clinical Data. Clinical Pharmacokinetics 50(6):349-69.June 2011.

22 https://www.plivazdravlje.hr/bolest-clanak/bolest/54/ Reumatoidni-artritis.html, pristupljeno 19.9.2022.

23 https://www.plivazdravlje.hr/aktualno/clanak/30657/Osteoartri­ tis-degenerativna-bolest-zglobova.html#40124 Pristupljeno 19.9.2022.

24 Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine. 2003 Jan;10(1):3-7. doi: 10.1078/094471103321648593. PMID: 12622457.

25 Majeed M, Majeed S, Narayanan NK, Nagabhushanam K. A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. Phytother Res. 2019 May;33(5):1457-1468. doi: 10.1002/ptr.6338. Epub 2019 Mar 6. PMID: 30838706; PMCID: PMC6681146.

26 Sengupta K, Alluri KV, Satish AR, Mishra S, Golakoti T, Sarma KV, Dey D, Raychaudhuri SP. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther.

2008;10(4):R85. doi: 10.1186/ar2461. Epub 2008 Jul 30. PMID: 18667054; PMCID: PMC2575633.

27 Italiano G, Raimondo M, Giannetti G, Gargiulo A. Benefits of a Food Supplement Containing Boswellia serrata and Bromelain for Improving the Quality of Life in Patients with Osteoarthritis: A Pilot Study. J Altern Complement Med. 2020 Feb;26(2):123-129. doi: 10.1089/acm.2019.0258. Epub 2019 Nov 1. PMID: 31674795.

28 Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res 1998; 3 (11): 511-4 29 Roy NK, Parama D, Banik K, Bordoloi D, Devi AK, Thakur KK, Padmavathi G, Shakibaei M, Fan L, Sethi G, Kunnumakkara AB. An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases. Int J Mol Sci. 2019 Aug 22;20(17):4101. doi: 10.3390/ijms20174101. PMID: 31443458; PMCID: PMC6747466.

9

Bioline

Nutramedic &Cosmetics

Reliable partner for your projects Bioline is an independent company specializing in providing a variety of pharmaceutical services.

T

hrough its representative office, it provides the opportunity to cooperate with a number of selected internationally renowned phar­ maceutical companies and manufacturers of medi­ cines, medicinal products, food supplements, cos­ metics and food.

As part of our offer, we offer a variety of potential projects and a variety of pharmaceutical forms tablets, capsules, sticks, orosolubile granules in stick, soft gelatin capsules, water-soluble powder sachets.

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We have been present on the market for 23 years, with always constant quality of service, which has been recognized by many satisfied customers. The companies that are service providers have been se­ lected with care and emphasis on quality, innovation, flexibility and speed of delivery of the desired pro­ ducts. These are refurbished companies from Portu­ gal, Italy, Poland, Spain.

Bioline participates in all projects, giving them ad­ ditional value in the form of proposals for new pro­ duct concepts, thanks to many years of experience in the international market. We regularly visit all major trade fairs in the industry (CphI, Vitafoods, Health In­ gredients, Food ingredients) to keep up with the news and maintain contacts with customers and service providers.

So far, we have participated in the successful im­ plementation of more than 50 projects.

The services we offer to our partners provide the opportunity to always find the most suitable solu­ tion.

In the category of food supplements we can offer: • Granule-based products: effervescent tablets, wa­ ter-soluble granules, water-free dissolving granules • chewable tablets, fast-dissolving tablets, sublin­ gual tablets, effervescent tablets, coated tablets, tablets • Capsules • Powder • Spray • Drops

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21

Nutramedic &Cosmetics

Curtis Health Caps

contract development and manufacturing services for pharmaceutical projects Curtis Health Caps provides soft gelatin capsules, non-sterile liquid products, and research and development (R&D) services for the pharmaceutical sector.

C

urtis Health Caps is a multinational contract development and manufacturing organisa­ tion (CDMO) specialising in soft gelatin cap­ sules, non-sterile liquid products, and research and development (R&D) services.

We offer a comprehensive range of solutions, from R&D services and regulatory audits to quality consultancy, production, storage and transport, all carefully tailored to the ever-changing needs of the market. Our services are in high demand from phar­ maceutical contract manufacturing companies.

We operate a modern and innovative machinery park in Poland that features a well-equipped R&D department, employing experts across a range of fields.

With over 30 years of presence in international markets, CHC has been recognized as a trusted part­ ner providing services to Clients from the pharma­ ceutical, food and cosmetics industries as producers of food supplements, medicinal products, medical devices, cosmetics and veterinary products.

22

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As a CDMO, Curtis Health Caps provides clients with high-quality service throughout the whole product development process, from initial concept to final product.

Our experienced team can offer professional sup­ port with formulation and choosing the most suit­ able packaging. This allows you to easily add to your portfolio and find new pharmaceutical products for in-licensing.

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Soft gelatin capsule development to client specifications

As part of the contractual production of medicinal products and food supplements, Curtis Health Caps allows clients to individually select the colour and shape of soft capsules to suit their specific require­

Nutramedic &Cosmetics ments and preferences.

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The encapsulation process’ specificity ensures the product keeps its microbiological safety without the use of preservatives, which is particularly im­ portant in products intended for children. In addi­ tion, the capsule shell is made from biodegradable and environmentally friendly components.

Development of pharmaceutical products in non-sterile liquid forms

Curtis Health Caps specialises in contract manu­ facturing medicinal products, food supplements and medical devices, as well as liquid forms of syr­ ups, suspensions, drops and sprays. We can manu­ facture non-sterile liquid syrups, suspensions, drops or sprays according to clients’ preferences and cus­ tomer needs.

Liquid-form products offer a wide dosage spec­ trum and have high absorption rates. They do not pose a risk of choking and are easier to swallow, making them more suitable to administer to children and elderly patients.

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Research and development services for pharmaceutical projects

Curtis Health Caps provides R&D services at all stages of development for capsules and non-sterile liquid products, from initial concept to finished product.

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Curtis Health Caps offers a wide range of services for manufacturing soft gelatin capsules and non-­ sterile liquid forms. These include developing for­ mulations for new products based on the latest market trends and literature, modifying existing product formulations, selecting raw materials of ade­ quate quality from certified suppliers, and develo­ ping technology for trial and pilot batches.

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Curtis Health Caps provides regulatory audits for a range of medicinal products and medical devices.

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According to our MIA (146/0129/15), Curtis Health Caps S.A. is currently entitled for: • manufacturing of non-sterile human medicinal pro­ ducts in the form of capsules with soft shell and liquids for internal use, including herbal products • batch certification • packaging of capsules (soft shell and hard shell), liquids for internal use and tablets • quality control testing • manufacturing operations, primary packaging and quality control testing of Investigational Medici­ nal Products in the form of liquids for internal use.

If you are interested in cooperating with us in the field of production activities, also in the develop­ ment of a medicinal product or its transfer, we are at your disposal.

Our manufacturing facility in Przeźmierowo, Po­ land, is certified as complying with the EU’s GMP standards and the eighth edition of the UK’s Brand Reputation Compliance (BRC) Global Standards. We also hold ISO 9001:2015, 14001:2015 and 13485:2016 certifications.

Distinguishing features

• Clear B2B model - the absence of our own brands is part of CHC's long-term strategy • Personal assistance at every step • Efficient and effective communication • Efficient determination of the terms of cooperation • High flexibility regarding the size of the produc­ tion batch • Manufacturing facility and modern laboratory • Customers’ production orders are always our pri­ ority • Ready to market products • Professional partner from idea to final product • Diversity of manufacturing/development in terms of product categories: medicinal products, medi­ cal devices, food supplements, cosmetics, veteri­ nary products • Short & flexible lead Times

Curtis Health Caps Wysogotowo ul. Batorowska 52 62-081 Przeźmierowo, Poland www.chc.com.pl www.linkedin.com/company/curtis-health-caps www.facebook.com/curtishealthcaps bd@chc.com.pl rd@chc.com.pl office@chc.com.pl

23

Nutramedic &Cosmetics

His Majesty

Iron

Standard iron preparations are accompanied by frequent gastrointestinal side effects.

For that reason, a new generation of oral iron preparations was developed for better tolerability and reduced side effects. These are preparations with heme iron in which the micronized form of iron is incorporated into liposomes, i.e., size of the iron particle is reduced to increase solubility and better absorption (sucrosomial iron).1 AUTHOR:

Natalija Kanački, MD, New Product Development Manager, Proximum d.o.o.

24

I

ron is an essential component of hundreds of pro­ teins and enzymes that support essential biologi­ cal functions, such as oxygen transport, energy pro­ duction, and DNA synthesis. Hemoglobin, myoglobin, cytochromes, and peroxidases require iron-contain­ ing heme as a prosthetic group for their biological ac­tivities.

Iron deficiency caused by insufficient iron level in the body is called sideropenic anemia. (Greek: sí­dē­ ros, iron). When the body's iron reserves are deplet­ ed, the symptoms of iron deficiency appear: fatigue, lethargy, weakened appetite, reduced physical strength, and resistance.

The amount of iron (in food or supplements) ab­ sorbed and used by the body is influenced by iron's nutritional status of the individual

and whether or not the iron is in the form of heme.

Heme iron is more readily absorbed and is less affe­c­­ ted by other dietary factors because it is absorbed by a different mechanism than non-heme iron. 2 Heme-iron is the form of iron most easily absor­ bed by the body. Heme-iron is highly bioavailable (15%-35%), and dietary factors have little effect on its absorption. In contrast, non-heme iron absorp­ tion is much lower (2%-20%) and strongly influenced by the presence of other food components. On the contrary, the quantity of non-heme iron in the diet is greater than that of heme-iron in most meals. Thus, despite its lower bioavailability, non-heme iron gen­ erally contributes more to iron nutrition than hemeiron.4,5

Nutramedic &Cosmetics Heme-iron comes mainly from hemoglobin and myoglobin in meat, poultry, and fish. Although heme iron accounts for only 10%-15% of the iron found in the diet, it may provide up to one-third of total ab­ sorbed dietary iron.6 Heme iron absorption is less in­ fluenced by other dietary factors than non-heme iron.

Plants, dairy products, meat, and iron salts added to food and supplements are all sources of non-he­ me iron. The absorption of non-heme iron is strong­ ly influenced by enhancers (Figure 1) and inhibitors (Figure 2) present in the same meal.7 Calcium inhibits the absorption of both heme and non-heme iron.8 In an attempt to improve body iron status, iron ab­ sorption is enhanced in individuals who are anemic or iron deficient compared to iron-replete individu­ als.

FIGURE 1 Non-heme iron absorption enhancers

Non-heme iron absorption enhancers

Vitamin C

Organic acids (malic, citric, tartaric...)

Meat, poultry and fish

Causes of iron deficiency anemia (IDA)

Multiple physiologic, environmental, pathological, and genetic causes of iron deficiency (ID) lead to IDA (Fig. 3).9

Iron homeostasis

Iron homeostasis is tightly controlled to avoid the toxic effects of excess iron in the form of harmful reactive oxygen species. Iron loss (cell shedding) is around 1 mg daily, with daily absorption limited to 1–2 mg to compensate for daily iron losses. However, the body requires about 25 mg of iron daily, mainly used to produce erythrocyte hemoglobin. The body recycles most of the needed iron from the break­ down of senescent erythrocytes by macrophages in the spleen to make it available to plasma transferrin.

This tight control of iron absorption and recycling is mediated through the hepatic hormone hepcidin.

and drops, coated and extended-release tablets and capsules. Iron formulations often contain vitamins such as ascorbic acid, cyanocobalamin, folic acid, and others for better utilization.

Oral iron preparations are available in both fer­ rous and ferric states. The most commonly available oral supplements include ferrous sulfate, ferrous glu­ conate, and ferrous fumarate gluconate. All forms are well absorbed but differ in elemental iron con­ tent. Ferrous sulfate is the least expensive and most commonly used oral iron supplement.5 There are preparations with iron originating from hemoglobin containing heme iron and others with chelated iron.

Chelated iron is a supplemental form of iron that has been chemically bound to amino acid to allow it to pass through the digestive system without breaking apart. It gets carried into the cell along with the ami­ no acid it is bound to for more efficient absorption.

The clinical research data is mixed as to whether che­ lated iron supplements are more effective for pre­ venting low hemoglobin levels.10,11 Studies have shown that iron bisglycinate and iron protein succinylate are associated with less gastro­ intestinal intolerance than ferrous sulfate, gluco­ nate, and fumarate for a comparable dose of ele­ mental iron but are more expensive.12 Heme-iron or heme-iron polypeptide (HIP) is a new generation oral iron which uses the heme porphyrin ring to supply iron to sites of absorption in the intes­ tinal lumen.13 Heme-iron is an organic form of iron with high bioavailability in the body and good gastroin­ testinal tolerance. The results of the study in which 77 women of reproductive age participated showed more efficient and better absorption of heme iron, compared to the non-heme form (iron fumarate), without unpleasant side effects.14 Also, the study on patients with chronic kidney disease not on dialysis (ND-CKD) found that heme-iron is similar in efficacy to IV (intravenous) iron sucrose in maintaining he­ moglobin with no differences in adverse events over six months.12 Heme-iron is on the food supple­ ments market as a combination of heme and nonheme iron (Globifer®). Heme-iron is very efficient, especially for pregnant women and women of re­ productive age – it is a form of iron with excellent gastrointestinal tolerance and almost no gastroin­ testinal side effects (nausea, cramps, obstipation).

In recent years, iron preparations obtained by new production technologies have entered the market.

Standard iron preparations are accompanied by frequent gastrointestinal side effects, sometimes FIGURE 2 Inhibitors of non-heme iron absorption

Prevention of iron deficiency

The four strategies for correcting micronutrient deficiencies in populations who need correcting iron deficiency, either alone or in combination, are food diversification, supplementation, food fortifi­ cation, and biofortification.

Iron supplementation

Many iron preparations are available with various amounts of iron, including iron salts, complexes, combinations, and different dosing regimens. They are available in regular tablets and capsules, liquid

Inhibitors of Non-heme iron absorption

Phytic acid (phytates)

Phytic acid Polyphenols (phytates)

Soy proteins

Calcium

25

Nutramedic &Cosmetics FIGURE 3

Multiple aetiologies for iron deficiency anemia

References: 1

Wessling-Resnick M. Iron. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed: Lippincott Williams & Wilkins; 2014:176-188.

2

Food and Nutrition Board, Institute of Medicine. Copper. Dietary Reference Intakes for Vitamin A, Vitamin K, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press; 2001:224-257. (National Academy Press)

3

Global Burden of Disease Pediatrics Collaboration, Kyu, H. H., Pinho, C., Wagner, J. A., Brown, J. C., Bertozzi-Villa, A., Charlson, F. J., Coffeng, L. E., Dandona, L., Erskine, H. E., Ferrari, A. J., Fitzmaurice, C., Fleming, T. D., Forouzanfar, M. H., Graetz, N., Guinovart, C., Haagsma, J., Higashi, H., Kassebaum, N. J., Larson, H. J., … Vos, T. (2016). Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013: Findings From the Global Burden of Disease 2013 Study. JAMA pediatrics, 170(3), 267–287. https://doi.org/10.1001/jamapediat­ rics.2015.4276

4

Abbaspour, N., Hurrell, R., & Kelishadi, R. (2014). Review on iron and its importance for human health. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 19(2), 164–174.

5

Saunders, A. V., Craig, W. J., Baines, S. K., & Posen, J. S. (2013). Iron and vegetarian diets. The Medical journal of Australia, 199(S4), S11–S16. https://doi.org/10.5694/mja11.11494

6

Hurrell, R., & Egli, I. (2010). Iron bioavailability and dietary reference values. The American journal of clinical nutrition, 91(5), 1461S–1467S. https://doi.org/10.3945/ajcn.2010.28674F

7

Hallberg, L., Brune, M., Erlandsson, M., Sandberg, A. S., & Rossander-Hultén, L. (1991). Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. The American journal of clinical nutrition, 53(1), 112–119. https://doi. org/10.1093/ajcn/53.1.112

8

Cappellini, M. D., Musallam, K. M., & Taher, A. T. (2020). Iron deficiency anaemia revisited. Journal of internal medicine, 287(2), 153–170. https://doi.org/10.1111/joim.13004

9

Duque X, Martinez H, Vilchis-Gil J, et al. Effect of supplementa­ tion with ferrous sulfate or iron bis-glycinate chelate on ferritin concentration in Mexican schoolchildren: A randomized controlled trial. Nutr J. 2014;13:71. doi:10.1186/1475-2891-13-71

10

Abdel Moety GAF, Ali AM, Fouad R, et al. Amino acid chelated iron versus an iron salt in the treatment of iron deficiency anemia with pregnancy: A randomized controlled study. Eur J Obstet Gynecol Reprod Biol. 2017;210:242-246. doi:10.1016/j. ejogrb.2017.01.003

11

A Physician’s Guide to Oral Iron Supplements, https://www.iron. sabm.org Accessed 30.9.2022.

12

Nagaraju SP, Cohn A, Akbari A, Davis JL, Zimmerman DL. Heme iron polypeptide for the treatment of iron deficiency anemia in non-dialysis chronic kidney disease patients: a randomized controlled trial. BMC Nephrol. 2013 Mar 20;14:64. doi: 10.1186/14712369-14-64. PMID: 23514036; PMCID: PMC3606612.

13

Hoppe, M., Brün, B., Larsson, M. P., Moraeus, L., & Hulthén, L. (2013).

Heme iron-based dietary intervention for improvement of iron status in young women. Nutrition (Burbank, Los Angeles County, Calif.), 29(1), 89–95. https://doi.org/10.1016/j.nut.2012.04.013

14

Gómez-Ramírez, S., Brilli, E., Tarantino, G., & Muñoz, M. (2018).

Sucrosomial® Iron: A New Generation Iron for Improving Oral Supplementation. Pharmaceuticals (Basel, Switzerland), 11(4), 97. https://doi.org/10.3390/ph11040097

Children in developing countries: • Decreased intake (malnutrition) • Chronic gastrointestinal blood loss (parasitic infections) • Decreased absorption (parasitic infections) • Inflammation (from chronic infections) Endurance athletes: • Blood loss from hemolysis • Chronic inflammation Elderly: • Decreased intake (malnutrition) • Gastrointestinal blood loss (benign or malignant conditions, druginduced) • Decreased absorption (atrophic gastritis, proton-pump inhibitors) • Chronic inflammatory conditions (including cancer) Chronic kidney disease: • Chronic blood loss (dialysis, use of anticoagulants) • Decreased intake (malnutrition) • Decreased absorption (proton-pump inhibitors) • Chronic inflammation • Decreased hepcidin clearance • ESA therapy Chronic heart failure: • Decreased intake (malnutrition) • Decreased absorption (edema) • Gastrointestinal blood loss (antiplatelet or anticoagulant) • Chronic inflammation (in early more than late stages) Obesity: • Decreased absorption (bariatric surgery, before positive effects on weight loss) • Chronic inflammation Inflammatory bowel disease: • Decreased intake (malnutrition) • Chronic gastrointestinal blood loss • Decreased absorption (surgical resection in Crohn's disease) • Chronic inflammation Major surgery: • Blood loss • Postoperative inflammation leading the patient to stop taking iron supplements and fail the prescribed therapy. For that reason, a new generation of oral iron preparations was develo­ ped for better tolerability and reduced side effects.

These are preparations in which the micronized form of iron is incorporated into liposomes, i.e., size of the iron particle is reduced to increase solubility and better absorption (sucrosomial iron).15

26

Nutramedic &Cosmetics

27

Nutramedic &Cosmetics

Impact of nutrients and dietary supplements on cognitive function Nowadays, dietary supplements aimed at improving cognitive abilities have more than ever broader target group – students who want to concentrate better, e-gamers who want better performance, stressed parents, people with post-covid…

AUTHOR:

Daria Šurić, M.Pharm.

T

he brain is a fascinating and complex organ that controls all functions in the body, pro­ cesses information from the outside world and embodies the essence of the mind and soul. In­ telligence, creativity, emotions and memory are just some of the many functions that the brain performs.

The brain gets information through five senses: vision, smell, touch, taste and hearing - often from multiple of them at the same time. It interprets the messages in such a way that they become under­ standable and meaningful, and saves information in the form of memory. In addition, it controls thoughts, speech, hand and leg movements and the functions of many organs in the body.

Healthy brain function implies the absence of dis­

ease and the maintenance of optimal cognitive fun­ c­tion. Under the concept of cognitive ability, a set of skills or mental abilities is considered that allow us to process all the information from the environment and to give the environment an adequate response.

Cognitive abilities include memory, attention, under­ standing and processing of information, and the abi­ lity to solve tasks. It is those mental abilities that help to understand the world around us and to pro­ cess stimuli that collect the senses of vision, smell, touch, taste and hearing. According to many experts, the set of all cognitive abilities makes up intelligen­ ce or intellectual capacity.

Memory and learning

Memory and learning are closely related, and the­ refore we often mix these concepts. However, ex­ perts dealing with this field consider them two sep­ arate phenomena. Learning is defined as a process that forms the consequential behavior, and memo­ ry, on the other hand, is the ability to remem­ ber past events.

For example, we master a foreign lan­ guage by learning it, but when we speak it, we use memory to remember the words we have learned.

Memory is important for any lear­ ning, as it allows you to store and re­ trieve the information we learn. Me­ mory is basically nothing more than a record that was created during the lea­r­­n­ing process. Thus, memory de­ pe­n­ds on what is learned. But learning also depends on memory, because the knowledge stored in your memory provi­ des a database with which you link new know­ ledge, by association. The more extensive the frame­ work of existing knowledge, the easier it is to con­ nect new knowledge with it.

Memory

Memory is a complex process that involves three stages: defining (deciding which information is im­ portant), storing and remembering. Different parts of the brain are involved in different forms of memory.

28

Nutramedic &Cosmetics The human brain coordinates and monitors a pro­ cess, called coding, to make an individual memorable event go from short-term to long-term memory.

Sensory memory collects the information pro­ vided by the senses and stores it in its original form, but very shortly (from several hundred milliseconds to one or two seconds). It lasts so shortly that it is of­ ten considered part of the process of perception.

Nevertheless, it represents an essential step for storing information in short-term memory.

Short-term memory, also called working memo­ ry, occurs in the prefrontal cortex. It stores informa­ tion for about one minute, and its capacity is limited to about 7 entries. For example, it allows you to dial a phone number that someone just specified. It also intervenes during reading to remember the sen­ tence just read, so the next sentence makes sense.

Short-term memory is an important step towards long-term memory.

Long-term memory is processed in the hippo­ campus of the temporal lobe and activated when so­ mething wants to be remembered for a long time.

This memory has unlimited content and duration ca­ pacity. It contains personal memories as well as facts and figures.

Skill memory is processed in the cerebellum, which transmits information to basal ganglia. It sto­res au­ tomatically learned memories such as tying shoes, playing an instrument, or riding a bike.

Healthy brain function implies the absence of dis­ eases and neurodegenerative disorders such as Alz­ heimer's disease, epilepsy, Parkinson's disease, mig­ raines, dementia, congenital neurological disorders, neuroinfective and neuroimunological disorders, neu­ romuscular disorders and nervous system cancers.

In addition, for brain health it is important to main­ tain optimal cognitive function. Proper nutrition is key to maintaining healthy brain function, and certain supplements can help to support cognitive abilities.

Ingredients and nutrients which are most effective for maintaining cognitive function

Extracts and substances that can improve cogni­ tive function include Bacopa monnieri plant extract, blueberry, caffeine, Ginkgo biloba, ginseng, omega-3 fatty acids, L-carnitine. It is also important and opti­ mal to take nutrients that are essential to maintain brain health - iodine, zinc, copper, vitamins B1, B3, B12 and folic acid.

Bacopa

Bacopa monnieri is a plant that has been used since ancient times in traditional Indian medicine to improve memory and reduce anxiety. Preclinical studies have shown promising results.

The 2021 systematic review included 32 studies that looked at the impact of bacopa on aspects of the cognitive function of healthy people, then peo­ ple with Alzheimer's disease and those with depres­ sion. Among them, 11 randomized controlled studies were included in the meta-analysis, all of which in­ volved examining memory and attention functions in a total of 645 healthy participants6.

A double-blind, placebo-controlled study, in which 125 mg of standardized Bacopa monnieri extract was

used 2 times a day, showed that this extract during the 12-week therapeutic period has a significant ef­ fect on mental control, improving memory associated with logical reasoning and related associative learn­ ing. Participants were selected based on criteria for the presence of age-related memory disorders, but without evidence of dementia or psychiatric disorders.

The plant Bacopa monnieri is on the list of permit­ ted substances according to the current legislation in Croatia, but there are warnings that must be writ­ ten on the declaration of the dietary supplement containing it: people taking the drugs should consult a doctor before taking it; it is not recommended for thyroid, asthma, emphysema, disorders of the diges­ tive and urinary systems and heart disorders, preg­ nant, lactating women or children.

Ginkgo

A 2020 meta-analysis, involving 7 randomized tri­ als with a total of 939 alzheimer's patients, receiving Ginkgo bilobae EGb-761 extract, showed an improve­ ment in cognitive function, while the impact on daily life was not observed.

A 2016 systematic review and meta-analysis, invol­ ving 21 randomized controlled trials with 2.608 par­ ticipants, concluded that in people with mild cogni­ tive impairment or Alzheimer's disease, ginkgo is po­ tentially beneficial for improving cognitive function, quality of life, activity, and overall clinical assess­ ment. However, due to the small sample, inconsis­ tent findings and methodological quality of the stud­ ies included in the review, more research is ne­eded to confirm the effectiveness and safety of ginkgo for the treatment of cognitive impairment and Alzhei­ mer's disease.

The dose of ginkgo extract is different in dietary supplements and in herbal remedies in Croatian and other markets, so it is best to consult with a pharma­ cist before taking it, since there is an impact of gink­ go extract on the parameters of blood coagulation.

According to the current legislation in Croatia, the maximum daily dose of ginkgo extract in dietary supplements is 80 mg. The above studies mainly used higher doses found in herbal remedies.

Blueberry

Blueberry contains a large amount of anthocyan­ in molecules that have a strong antioxidant action.

Blueberries can be consumed in the form of an ex­ tract or as fresh or frozen fruits. The dose required to achieve a health effect on the brain and blood vessels is approximately 5.5 g of dry powder or 500 mg of anthocyanin. This would correspond to the amount of approximately 20-60 g of dried blueberries.

29

Nutramedic &Cosmetics Blueberries have proven effective in people expe­ riencing impairment in cognitive function, but there are also indications that they could improve the cognitive abilities of younger people as well.

In the study, a group of elderly people, over the course of 12 weeks, consumed blueberry juice daily, which contained 428-598 mg of anthocyanin. There was an improvement in memory and learning abili­ ties, while at the same time the parameters of glu­ cose in the blood showed a downward trend. This initial study laid the groundwork for future clinical trials related to blueberry supplementation as a pre­ ventive measure in cognitive aging.

Caffeine

Numerous studies have shown that it reduces the symptoms of mental fatigue, both alone or in combi­ nation with glucose. Caffeine is a powerful stimu­ lant, as it sensitizes neurons and enhances mental stimulation. Its effectiveness on improving cogni­ tive function has been proven in many studies. Dos­ age of 46 mg of caffeine in combination with glu­ cose has shown an effect.

A randomized controlled study that addressed subjective, behavioral and psychological effects on acute caffeine intake in participants who are not ad­ dicted to caffeine, showed that in a single dose, in the amount contained in one cup of coffee, it pro­ duces a stimulating effect and improves efficiency.

Omega-3

Omega-3 unsaturated fatty acids have been prov­ en effective in attention deficit hyperactivity disor­ der (ADHD). Improvements were observed in the wor­ king memory function segment and attention was improved. The dose that has proven effective in chil­ dren with ADHD is from 300 mg of DHA and higher.

Saffron extract, L-teanin, L-carnitine and zinc their effectiveness in the field of brain health have de­mon­ strated mostly in studies focused on ADHD in children.

Among other substances interesting to add to die­ tary supplements aimed at maintaining brain health and cognitive abilities we can also mention phos­ phatidyl serine, then green oat extract, citicoline and resveratrol.

Probiotics are also gaining increasing importance, because the knowledge that the microbiota in the intestines plays a big role in mental health, stimu­ lates interest in probiotics in this segment of appli­ cation as well.

Conclusion

Nowadays, dietary supplements aimed at improv­ ing cognitive abilities have an ever-expanding tar­ get group. Unlike before, the younger population also becomes aware of the importance of this seg­ ment - from students who want to concentrate bet­ ter, the so-called "1990s". E-gaming populations that want better performance, parents who "navigate" through everyday stress and tasks, to older popula­ tions or people with post-covid syndrome.

With the expansion of the target group, there is also a need for new ways of application, so increas­ ingly on the meaning they acquire practical on-thego forms, or gummy bears.

30

Prebiotic effect evidenced for chicory root fibres Intake of chicory root fibres increases Bifidobacteria and supports bowel function

A

new systematic literature review with meta-analyses, conducted by Dávid U. Nagy et al.1, demonstrates that chicory root fibre intake (starting at 3g/ day) promotes significant growth of Bifidobacteria in the gut microbiome in all age groups and improves bowel function parameters. It is the first study of this kind, based on randomised control trials, that has investigated the effect of inulin-type fructans derived from chicory root on Bifidobacteria abundance in gut microbiota and health-related outcomes.

Included in the systematic review with meta-analyses, considered the stron­ gest methodology in the hierarchy of scientific evidence, were 50 human inter­ vention studies, with a total of 2,495 participants. These were selected based on an extensive literature search and review process that followed the guidelines of the Cochrane Handbook for Systematic Reviews and Interventions2. This research evidenced that inulin, oligofructose and combinations thereof, derived from the chicory root as the source of origin, act as a bifidogenic factor, promoting the selec­ tive growth of Bifidobacteria. The systematic review with meta-analyses also de­ monstrates that chicory root fibre is a prebiotic that complies with the ISAPP (Inter­ national Scientific Association for Probiotics and Prebiotics) definition of prebiotics.

The researchers further reported that the bifidogenic effects of the chicory root fibres were accompanied by improved bowel regularity. This was validated by increased stool frequency in healthy adults, and by softer stools in healthy in­ fants and children.

Commenting on the findings, Anke Sentko, Vice President Regulatory Affairs and Nutrition Communication at BENEO said: “I am extremely pleased that this detailed critical systematic review with meta-analyses has been conducted. Fol­ lowing the highest quality scientific evidence methodology, the prebiotic effect of inulin-type fructans sourced from the chicory root is confirmed. It yet again shows that integrating chicory root fibres into a person’s daily diet supports Bi­ fidobacteria and thus their gut microbiome, while also improving the bowel func­ tions of the very young to the very old.”

BENEO’s prebiotic fibres, Orafti® Inulin and Oligofructose, are inulin-type fruc­ tans. They are natural, non-GMO, clean label prebiotic fibres that are derived from chicory root via a gentle hot water extraction method, unlike some other fi­ bres that are artificially or chemically made. They can be used in a wide range of food and beverage applications including baby food, according to national legis­ lations. As proven prebiotics, chicory root fibres (inulin, oligofructose) support a healthy gut microbiota and selectively promote the growth of beneficial micro­ organisms, such as Bifidobacteria, in the gut. Chicory root fibres are the pre­ ferred food for those good microorganisms and thus help them to grow and mul­ tiply. Due to the increased bacterial metabolism in the large intestine, regularity is improved.

References: 1

Nagy DU, Sándor-Bajusz KA, Bódy B, Decsi T, Van Harsselaar J, Theis S &Lohner S (2022) Effect of chico­ ry derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta analyses. Critical Reviews in Food Science and Nutrition. Published 14 July 2022, DOI: 10.1080/10408398.2022.2098246

2

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from https://www.training.cochrane.org/handbook

Source: www.beneo.com/beneo_news/prebiotic-effect-eviden­ced-forchicory-root-fibres-by-the-first-systematic-review-with-meta-analyses

Nutramedic &Cosmetics

MEDICINAL PLANTS PHOTO HERBARIUM

Chicory

Chicory (Cichorium intybus L), a perennial herbaceous plant, is widespread throughout Europe. It is rich in inulin, which acts as a prebiotic and stimulates the growth of beneficial bacteria in the intestinal microflora.

C

hicory (Cichorium intybus L.) is a perennial herbaceous plant from the family of Astera­ ceae. The stem is erect, pubescent, woody and angular, branched in the upper part. It grows up to one meter in height. The root is spindle-shaped, well branched, very tough, yellowish white in color.

The ground leaves are collected in a rosette, they are oblong, they are deeply carved and have a short pe­ tiole, the upper leaves are alternating, sedentary and cover the stem, the leaves themselves are bare or on the reverse are pubescent. The flower heads have a diameter of 2-3 cm and occur from June to October, grow individually from the armpits of the leaves and on the tips of the stems. The flowers are bisexual, light-blue, tongue-shaped. Ovula grows with one seed embryo. It blooms from June to October. The flowers are only open during the morning hours and they close when cloudy weather arrives. The whole plant contains milky juice with a bitter taste, espe­ cially when it is young.

Use for medicinal purposes

Leaves, flowers and roots of cichory are used. As a bitter plant, it is used to improve the work of bile and stimulate appetite. The medicinal part is the root that is extracted in autumn or spring but since the plant is solid and durable, it is very difficult to get it out of the ground. It contains 15-20 (-40)% inulin, 20% fruc­ tose, bitter substances and pectin. It has a bitter taste, stimulates the secretion of bile and acts as a mild choleretic.

It is dried, fried and ground and used as a prepara­ tion for making substitute for coffee. There is a deli­ cious mixture as an alternative to coffee that can be made by grinding the chicory root and mixed with acorns, barley and rye.

The leaves are harvested young in the spring be­ fore flowering, when they are bitter but they are co­ oked they have a good taste. They contain 40-50 mg % of vitamin C and 6-14 mg% carotene. Young buds can be pickled and open flowers are added to salads.

Cichorii radix is dried chicory root: Cichorium in­ tybus L., Cichoriaceae

• fructose monomer connected by β-1.2 - connec­ tion, terminally bound glucose in α-configuration • bitter glycoside intubin • lactupicrin, 8-deoxylactupicrin (in milky secret) • phenolcarboxylic acids: chicoric acid.

Usage

Inulin acts as a prebiotic and as such stimulates the growth of desirable bacteria in the intestinal mi­ croflora. Prebiotics stabilize the intestinal mucosa, normalize intestinal permeability and prevent the growth of pathogenic microorganisms. In the body, only a small part of the inulin is enzymatically de­ composed and reabsorbed, most of it comes into the colon undeveloped. Intake of inulin as indigestible ingredients have a beneficial effect on constipation.

Inulin as a dietary fiber affects the absorption of nutrients, especially carbohydrates. It leads to a de­ crease in gluconeogenesis and a favorable effect on diabetes mellitus. It stimulates the secretion of bile and acts as a mild choleretic (bitter substance), and is used for dyspeptic difficulties.

Literatura:

Flora Croatica database, hirc.botanic.hr Cikorija https://www.plantea.com.hr/cikorija Prof.dr.sc.Zdenka Kalođera, Sveučilište u Zagrebu, Farmaceutskobiokemijski fakultet, Farmakognozija II, Zagreb, 2006/2007.

TAXONOMY kingdom: Plantae order: Asterales

family: Asteraceae

genus: Cichorium

species: Cichorium

intybus

common name

Cichory, common chicory, wild chicory, coffee chicory, coffee weed, succory, wild succory, blue saisy, blue sailors, achicoria (Spanish), Wegwarte (German), chicorée (French) flowering time

VI, VII, VIII, IX, X month

Ingredients

• inulin (15-40%, in culture up to 70%) - polyfructo­ side, consists of fructose units (β-D-fructofura­ nosis);

31

Nutramedic &Cosmetics

Unique textures via natural-derived modifiers Although creating cosmetic products with unique textures looks like a lot of fun, it requires a balanced combination of science, art, imagination and persistence. There are many ingredients that can be used to aid in creating natural textures. Recent discovery of using xanthan gum and alginates as natural alternatives bridges the gap to the challenges of formulating natural textures.

AUTHORS:

Michał Stepulak, Senior Technical Manager Personal Care, Head of Warsaw Formulation Center, BASF and Aleksandra Pienczykowska, Operational Marketing Manager CEE, BASF

32

Y

ou have had a long day at work, your eyes are tired, and you have just put the kids to bed.

Your evening routine is your 'me time'. The creamy foam of your cleanser feels both nourishing and refreshing. Your serum has a pleasantly smooth feel, blends in quickly and does not feel sticky at all.

Your jar of moisturiser always looks inviting, beca­ use you know the texture is pillowy soft and light yet feels so comforting on your skin. You feel like you ha­ ve taken care of yourself, even for just a little while.

The texture of each of these products plays a cri­ tical role in building an emotional connection with your customer that can lead to long-term brand lo­ yalty. These unique textures add a layer to the pro­ duct experience, in addition to delivering basic func­ tionality.

The most experimental formats could be consid­ ered 'transformational', such as gel to oil, balm to powder. or serum to oil, where the application be­ gins as one form and transforms into an obviously different form for skin feel. Even more engaging are food-inspired products and unique formats like ice cream, jelly, smoothie, pudding, caviar, pearls, or spon­ ges that invite consumers to have fun with their rou­ tines.

When formulators are tasked to develop these uni­ que textures, a robust toolbox is required. Preferab­ ly this toolbox should be comprehensive and con­ tain a plethora of natural ingredients such as thick­ eners, emollients, emulsifiers, waxes, and more. As the demand for unique textures is mostly dependent on the use of polymeric thickeners. They provide form

Nutramedic &Cosmetics and structure to the formula and usually use syn­ thetic derivatives of acrylic acid, such as carbomer.

There are natural products available in the market that could be considered when choosing natural thickeners, such as polysaccharides; however, there are challenges and limitations when using these in­ gredients. They are usually stringy, difficult to pro­ cess, and do not yield a rigid structure and smooth consistency that can normally be achieved using acrylic acid- derived polymers.

BASF has identified a naturally derived system to replace carbomer hydrogels that can be used in de­ veloping these textures, by combining xanthan gum and alginates.

combinations show similarity in texture and rheo­ logical behavior between a carbomer-based hydro­ gel and the natural system using xanthan gum and alginates.

FIGURE 1 Flow (stress) sweep experiment

Natural alternative to carbomer

So, you want to create personal care formulas with different textures? You really like that gel lo­ tion that transforms to oil when applied, and that smoothie lotion that really looks creamy and invit­ ing. Now you are tasked to make one with all-natural ingredients preferably certified by COSMOS or the Natural Products Association (NPA) or has a high naturality index based on IS0-16128. Great, but the benchmarks use carbomer as thickener! This task will not be easy.

Fortunately BASF identified two key ingredients that can be used to increase the chance of success­ fully meeting your target. We combined two natural­ ly occurring anionic polysaccharides, Verdessence Xantan (INCi: Xanthan Gum) and Verdessence Algi­ nate (INCi: Algin) to achieve a hydrogel that is similar in structure to carbomer Xanthan gum is an excel­ lent natural polymer that could aid in the thickening of water as well as a stabiliser. When processing xan­ than gum, sufficient agitation is necessary to allow proper hydration in water. Although a decent alter­ native, xanthan gum alone usually gives a slimy and gelatinous texture which is far from the rigid and smooth texture that is desired when creating a hy­ drogel.

To improve this texture, BASF combined xanthan gum with algin reacted with calcium ions. Alginic ac­ ids (alginates) are polysaccharides isolated from ma­ rine brown algae and from bacterial fermentation. It is composed of two different monosaccharides, D-mannuronic acid and L-guluronic acid, both of which have carboxylic acid groups. These carboxylic acid groups, when reacted with polyvalent cations such as calcium ions, cause inter-polysaccharide binding called 'junction zones', facilitating viscosity increase until a gel is formed.

So, what is the sweet spot? We evaluated different ratios and concentrations and identified that to cre­ ate a hydrogel similar to one containing close to 0.5%w/w of carbomer neutralised with aminometh­ ylpropanol, we need somewhere between 2-3% of combined xanthan gum and alginates activated with calcium salts, Preferably with the ratio of two parts xanthan gum to one part alginates reacted with ei­ ther calcium sulfate or calcium citrate. This texture comparison or similarity can be evaluated visibly with the naked eye as well as using rheological equipment.

We used the DHR-1hybrid rheometer and stable mi­ cro system texture analyser to understand the rheo­ logical behaviour as well as the rigidity of the hydro­ gel formed. As seen in Figure 2 and 3, the suggested

Measured on DHR1 Hybrid Rheometer using 400 mm sandblast parallel plate, shear rate conditions; 1.0e3, temperature 250C

FIGURE 2 Firmness of Gels

Measured using micro system textures analyser will ball probe.

Five replicate measurement run for each

Handling alginates with a little TLC

Like xanthan gum, algin requires special handling, such as using adequate agitation with sufficient vor­ tex while slowly adding into water to allow proper hy­ dration. Ensuring that the water solution is at a high­ er pH also helps with the dispersion. When not react­ ed with calcium ions, alginates are inefficient thick­ eners that usually give serum-like structure with a slippery feel.

When in contact with calcium ions, it forms a rigid hydrogel which, when combined with xanthan gum, forms a texture similar to carbomer as previously mentioned.

However, careful handling is necessary to create a successful gel since alginates are very sensitive to cal­ cium ions. Over-addition of calcium ions could lead to precipitation of the gel from the aqueous solution.

Realising that this can be a challenge particularly

33

Nutramedic &Cosmetics FIGURE 3 Gel firmness of carbomer vs. 1% algin

with 0.4% calcium citrate

Using stable microsystem texture analyser with ball probe to measure firmness of the gel; five replicate measurements were run for each gel’ peak force is reported in N. carbomer peak force: 0.6949n algin + calcium citrate: 0.7177N

in production scale, BASF investigated the impact of using different calcium salts in processing time.

Using the same combination of xanthan gum and alginates, we investigated calcium chloride, calcium sulfate and calcium citrate, respectively. As expect­ ed, the reaction of alginate with calcium chloride was instant and led to either precipitation or over gela­ tion of the hydrogel.

Therefore, using calcium chloride as the reactant TABLE 1

Formulation

5 hrs curl retention at 250C/90%RH

Bending stiffness at 210C/40%RH

0.5% Carbomer + 2% PVP

38 +/- 7%

309 +/- 34

2% Xanthan Gum + 1% Algin

100 +/- 8%

378 +/- 76

34

poses a challenge if you want to achieve a homoge­ nous gel with alginates. The reaction when using cal­ cium sulfate and calcium citrate is not as rapid and allows better processing when making the aqueous hydrogel. Calcium sulfate, however, is not readily soluble in water, so it needs to be pre-solubilised in a solubiliser and homogenized in a separate water solution. Nevertheless, once in solution, calcium sul­ fate still allows better handling of alginate gels com­ pared to calcium chloride.

Calcium citrate offers the best performance when processing to make the gel. It is easily dispersible in water, does not require additional steps, and allows better control for gel formation. Calcium citrate with algin forms a translucent to opaque gel depending on concentration. Addition of glycerin or other solu­ bilisers can help reduce opacity of the gel (Figure 3).

Understanding that calcium citrate enables ease of processing, we looked at the possibility of using algin as the single thickener in gel systems. Further analysis of algin combined with calcium citrate shows that it is the ideal combination to achieve rigid gels and an effective alternative to carbomer. We postu­ late that the size of the calcium salt and the counte­ rion helps delay the reaction of calcium ions with the carboxylic group of alginates, thereby allowing the smooth formation of the hydrogel.

More than just a thickener...

Although xanthan gum and alginates are known to be rheology modifiers, studies have proven that they offer more than just thickening properties. For ex­ ample, recent work on styling gels has shown that they are both are ideal candidates to provide both naturality and performance. They offer excellent styl­ ing properties such as high bending stiffness and long-lasting resistance to high humidity. These pro­ perties were proven using the bending stiffness and curl retention methods established within BASF.

Nutramedic &Cosmetics FIGURE 4 Consumer test

80 60 40

74% 59%

74% 56%

65%

71%

20 0

Glycerin 3% Algin 1% 15 minutes: "My skin feels intensly hydrated"

15 minutes: "My skin looks and feels more supple"

It is worth mentioning that when used in styling these 'thickeners' can keep pace with the standard carbomer and PVP combination (Table 1). In fact, im­ provement in humidity resistance as well as reduced flaking was observed.

Alginates have proven to be a versatile, multifunc­ tional ingredient that offers additional benefits. In skin­ care application, as consumer panel reported that al­ gin offered perceivable enhanced feel on the skin, lea­ ving the skin feeling hydrated and looking more sup­ ple and radiant (Figure 4).

Building up your toolbox

Although creating cosmetic products with unique textures looks like a lot of fun, it requires a balanced combination of science, art, imagination and persi­ stence. As mentioned previously, there are many in­ gredients that can be used to aid in creating natural textures. Our recent discovery of using xanthan gum and alginates as natural alternatives bridges the gap to the challenges of formulating natural textures.

What are transformational textures? Simply de­ fined, they are products that start as one form and transform into another when applied to the skin.

These are usually in gel, cream, balm, and powder forms and the transformations vary depending on the formulation which is often influenced by multi­ ple factors such as tactile properties salt tolerance, melting point, or pressure.

The combination of xanthan gum and alginates provides an easy to create gel-to-oil lotion. The hy­ drogel is formed using the natural polymers that give the rigid gel structure with a smooth consisten­ cy when applied on the skin. The 'transformation' during application is provided by the carefully se­ lected oils and emollients.

We prefer to use our natural, silicone alternative Coco-Caprylate and Coco glycerides for non-greasy and caring after-feel. For a powdery after-feel, the fast-drying Tridecane/ Undecane excellent natural alternative to cyclomethicone. When creating food-in­ spired formulations there are many possibilities. The combined balance of using a hydrogel system and the choice of waxes and butters help develop food-in­ spired textures such as pudding, souffle and butter.

The use of these specialty ingredients, including Shea Butter and Shorea Stenoptera Seed Butter, pro­ vides additional structure to the hydrogel, thereby

15 minutes: "My skin looks noticebly radiant"

giving it the food-like consistency while allowing ex­ cellent absorption on the skin for a nice pampering experience.

Conclusion

As consumers look for more from their products than just functionality, there is a clear need for ef­ fective natural alternatives to popular synthetic systems. A combination of Verdessence Alginate, Verdessence Xantan and calcium salts can be used to achieve carbomer-like structure and texture in hydrogels. After researching three different calcium salts, calcium chloride, calcium sulfate, and calcium citrate, it was determined that calcium citrate is preferable due to ease of processing. Not only that, but 1.00% Verdessence Alginate can be used as the sole thickener when reacted with 0.40% calcium ci­ trate. This combination results in a gel with stiffness comparable to 0.50% carbomer.

In addition to being excellent thickeners, xanthan gum and alginates can be used in styling products, providing high bending stiffness and long-lasting resistance to high humidity. Alginates, specifically, are also great for use in skin care applications for enhanced hydration feeling on the skin, as well as more supple and radiant looking skin as reported by a consumer panel.

Now that you know it is possible to create engag­ ing fun, transformative textures with natural ingre­ dients, these materials are in your toolbox and you have a menu of naturally derived ingredients to choose from for your formulations.

distributed by: Cos Chem d.o.o., Podgaj 2, 10000 Zagreb, Croatia

www.basf.com

www.coschem.hr

www.carecreations.basf.com

tea.visek@coschem.hr

35

Nutramedic &Cosmetics

Probiotics in cosmetics: probiotic skin care It is considered that topical application of probiotic based products selectively increase the number and activity of „good bacteria“ and thereby improve the functioning of the microbiome. „Microbiom friendly“ products become a new market focus.

AUTHOR:

Lana Brkić, M.Eng.

Introduction

The skin is the covering organ of the human body.

Its main function is to protect body from external harm, forms a barrier to physical and chemical influ­ ences. It also represents a barrier to factors that af­ fect immunity, and radiation as well. The skin also regulates the body temperature and prevents water and lipid loss.

Microorganisms reside on human skin with the main function of supporting its healthy barrier function.

Probiotics are well known as “good bacteria“ that support good health and positively effect immune system. They improve the imbalance of the host bacteria by helping eliminating pathogen bacteria or complement the reduction of necessary non-patho­ genic bacteria.

Lately, probiotics are increasingly recognized for topical application with beneficial effects, at the site of application, for the treatment of different skin disorders. Therefore, the human skin microbiome gains interest in the field of the development of new

Figure 1

Factors influencing the composition and function of the human skin microbiota and its function

Challenges in exploring and manipulating the human skin microbiome, Boxberger et al., Microbiome (2021) 9:125 https://doi.org/10.1186/s40168-021-01062-5

36

cosmetic products.

The skin microbiota

The skin hosts the commensal microbiota, com­ posed of diversity of microorganisms including bac­ teria, yeast, fungi, viruses and they live in close rela­ tionship with the host, in a specific part of the body.

Microbiota complements the skin barrier to give a support in protecting the body from environmental influences. In a healthy microbiota, commensal mi­ croorganisms live together in an equilibrium. Com­ mensal strains are those microbes residing on the skin or mucosa without any harmful impact and thus prevent invasion of pathogens. Disruption of the composition of the skin microbiome is connected to the immune system and it leads to skin disorders.

Disruption causing factors, the environmental stres­ ses are climate, humidity, temperature, pH. Nutrition, lifestyle, infection, medication intake and hormonal imbalance are also influencing the balance. Disbal­ ance of the microbiota equilibrium may lead com­ mensal microflora to shift to pathogenic microflora and is known as „dysbiosis“. The skin barrier be­ comes weaker, skin pH raises and water loss increas­ es. Skin changes occur, the appearance of the skin, it loses its glow, it becomes sensitive, wrinkles begin to form. Dysbiosis, furthermore, can lead to pathologi­ cal skin conditions, such as eczema, acne, atopic der­ matitis, rosacea and dandruffs, with even serious signs of inflammation, like itching and scaling.

The microbiome is in science defined as a collec­ tion of microorganisms that reside on the skin, con­ sidered as genomes present on the skin.

Diversity of microorganisms and their distribu­ tion across the human skin is influenced by charac­ teristics of the host such as age, gender, genetic pre­ disposition, site of the skin, skin pH, sebum secre­ tion, intensity of sweating, body hair growth, daily hygiene habits and cosmetic products usage. Thus, every person has its unique microbiome.

The microbial community of the skin differs in three groups of microorganisms colonizing the skin.

The resident group is a base one and permanent. The transient group appears regularly and occasionally depending on the environment. The temporal group of microbes exist on the skin for a short time, for a few hours or days. When all these parts of microbi­ ome, the resident, transient and temporal, are in bal­ ance, the skin microbiome support properly skin's barrier and immunity function.

The residing phyla commonly consists of Actino­

Nutramedic &Cosmetics bacteria, Firmicutes, Proteobacteria and Bacteroides.

Gram-positive bacteria, such as Staphylococcus, Cu­ tibacterium and Coryneabacterium are dominant ge­ nera, while gram-negative bacteria, including Ente­ ro­bacteriaceae, are considered transient micro­bes.

At forehead, a sebaceous skin site, mainly Propibac­ tericum species are present. Armpits, navel, as more moisture areas, are colonized with a variety of diver­ se species, predominated Staphillococcus and Cory­ nebacterium species. Dry area, like volar forearm, is colonized by the widest diversity of species, includ­ ing β-Proteobacteria and Flavobacteriales. Malasse­ zia fungi are prevailing genus of fungi in skin and their distribution also depends on skin site, mainly on the sebum rich area of the skin and scalp. Malas­ sezia spp. are linked to the appearance of scalp dis­ order dandruff. Dandruff can cause complications on the skin, as seborrheic dermatitis. It is considered that, in this situation, there was an imbalance in Cu­ tibacterium and Staphylococcus species.

The individual microbial diversity is specific for each individual and, as such, it remains stable for some time. Therefore, it is considered that a balance has been established between the skin and the microor­ ganisms that live on it, over a long period of time, and that external and other influences cause the change of microorganisms from commensal to pathogenic form, resulting in various clinical pictures of changed skin conditions.

Importance of probiotics

Probiotics are generally considered as “bo­ dyfriendly” as they can confer health benefits. Probiot­ ics, when applied topically, effect the skin microbiot­ ic balance by influencing the composition of skin mi­ croflora. Positive influence on skin dysbiosis, in the literature, is discussed in two directions. Defending a skin’s barrier by influencing directly at the site of the application and by producing antimicrobial peptides that have implications on skin immune system and thus inhibit the growth of pathogenic microorgan­ isms and prevent their colonization.

Probiotics have the ability to restore the micobi­ ome and thus renew and strengthen the skin’s barri­ er, and consequently, they play a vital role in enhanc­ ing the overall skin appearance, improving skin con­ ditions and the function of the skin.

Bringing microbiome in balance and restoring the skin’s equilibrium, the following implications can be recognized: • reinforce the skin’s natural defenses against envi­ ronmental invaders • strengthen the immune skin system • maintain a healthy pH balance • stimulates the metabolic activity of skin cells • retain moisture and lipids level • reduce the factors that trigger sensitivity of skin • improve the appearance of dryness and dull skin

TABLE 1 Market available personal care probiotic-based products

Probiotic bacteria / lysate

Claim

Type of cosmetic product

Bifida ferment lysate, Lactobacillus

Anti-aging, regeneration, nourishing, smoothing, resto­ ration of density

Face serum for all skin types

Bifida ferment lysate

Strengthens the resistance of the skin's protective layer

Face serum for acne prone skin

Bifida ferment lysate

Better barrier function and decreased skin sensitivity.

Face cream and mask

Lactobacillus

Balancing the skin's natural microbiome, protection from external influences, strengthening

Regenerating eye cream

Lactobacillus

Hydration, brightening, against dark circles

Repairing eye mask

Lactobacillus ferment

Deodorant protection while allowing skin’s physiological perspiration process, Respecting skin microbiome

Deodorant

Kluyveromyces/ Lactobacillus/ Lactococcus/ Leuconostoc/ Saccharomyces filk ferment filtrate

Scalp restoration, hair nourishing

Restorative hair shampoo

Lactobacillus ferment

Preserves scalp sweating and greasy

Hair shampoo

Lactobacillus ferment

Preserves scalp sweating and dandruff

Hair shampoo

Lactobacillus

Strengthen the skin’s delicate microbiome protective barrier

Cleansing milk

Lactobacillus ferment lysate, Lactobacillus ferment lysate filtrate

Hydrating hands skin, softening skin, maintaining a well balanced microbiome

Hand cream

Lactococcus ferment lysate

Stimulate skin-cell renewal, reinforce skin barrier

Facial pads

Lactococcus ferment lysate

Enhance skin's immune function

Face serum for sensitive skin

Bifida ferment lysate

Moisturizes and restores the skin

Face serum

37

Nutramedic &Cosmetics • reduce the appearance of wrinkles • help soothing irritations and calm the skin

Probiotics in skin care

In recent years, the number of studies and re­ searches on topical application of probiotics on the skin has increased significantly. The findings have produced an increasing body of evidence that probi­ otics have implications for skin microorganism im­ balance and help to enhance the skin conditions.

Although these are still preliminary results, while effects on the microbiom and its functionality should be explored in more details, they gave a personal care industry a push to incorporate probiotic actives in new cosmetics products. It is considered that topical ap­ plication of probiotic based products selectively in­ crease the number and activity of „good bacteria“ and thereby improve the functioning of the microbiome. „Microbiom friendly“ products become a new market focus.

Types of cosmetic products already marketed to contain probiotics are, in face care category: cream, serum, mask, gel, cleanser, exfoliant, foundation; in body care category: balm, deodorant; in oral care ca­ tegory: toothpaste, mouthwash; in hair care catego­ ry: shampoo, hair mask.

The most common ingredients listed are: Lacto­ bacillus ferment, Bifida ferment lysate, Lacococcus ferment lysate, Lactobacillus.

Most of the marketed products are targeting skin appearance, mainly associated with ageing, moistu­ rization and lipid level, but also disorders like dan­ druff and acne.

In table 1 are shown market available types of cos­ metics products, with probiotic ingredients incorpo­ rated and benefits claimed. Products are found on the internet.

The claims on the products are mainly associated with healthy and balanced microbiome, reinforcement of skin barrier and improvement of skin complexion.

A cosmetic product, defined as per EU Regulation 1223/2009. is any substance or mixture intended to be placed in contact with the various external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance and/or correcting body odours and/or protecting them or keeping them in good condition. In line with this definition, no health claims are allowed on cosmetic products. Thus, manufacturers of personal care products contain­ ing probiotics should not declare any health claims on the packaging. In addition, in case of any efficacy claims, the EU regulation require the claim to be supported by “adequate and verifiable evidence.” The manufacturer also must ensure the safety of the pro­ ducts that will be marketed.

The personal care industry is facing challenges in developing topical formulations to maintain probi­ otic viability and keep probiotic effect.

Conventional cosmetic products contain preser­ vatives with the function of inhibiting the growth of microorganisms, as cosmetic products are not pro­ duced in sterile conditions and the preservation is required during the usage of product. If probiotic microorganisms are added to the cosmetic product

38

in form of living microorganism, then the preserva­ tive would inactivate them in a very short time. For this reason, live probiotics are only added to preser­ vative-free formulations or when products are pac­ ked in an airless type of packaging.

To overcome these obstacles with living bacteria, manufacturers use non-living ingredients, probiotic lysates or ferments. They are obtained from probi­ otic bacteria, contain fragments of bacteria cell or its metabolites, also providing skin beneficial activi­ ty like living ones, referred to as a postbiotics. As they are directly derived from probiotic bacteria, easier incorporated in cosmetic product, keeping their structure, postbiotics are considered as a good way to deliver probiotic benefits.

When live bacteria, as probiotics, are incorporated in skin products, prebiotics are recommended to be added also. Prebiotics are ingredients that promote the growth of probiotics and support living bacteria of probiotics to work as efficiently as possible. Pre­ biotics are the “food” for probiotics, and they help them to thrive. Prebiotics are added to cosmetic formula as xylitol, rhamnose, glucomannan or oligosaccharides.

In such a way, scientists who work on the develop­ ment of cosmetic product formulations have both options and challenges to create products that will give the best effects of probiotics to the skin. Nev­ ertheless, even though the investigations on the ef­ fects of probiotics have increased recently, there is still a lack of studies to determine their efficacy and mechanism of action. The clinical studies should al­so assess side effects and adverse reactions.

In terms of regulatory aspects, there are major shortcomings. Safety of probiotic-based products should be first concern, but also labelling of such products and acceptable claims should be defined.

Personal care industry will further focus their in­ novations on marketing skin care products on probi­ otics basis. Their development will grow as their ef­ fectiveness will be further proven by clinical studies and supported by scientific evidence. It is likely that topical application of probiotics will strengthen its role of enhancing the skin’s natural barrier, have positive implications on skin disorders and help en­ hance the beauty.

References:

Tavaria, F. K. (2017). Topical use of probiotics: The natural balance.

Porto Biomedical Journal, 2(3), 69–70. https://doi.org/10.1016/j.pbj.2017.02.003 Huang, M.-C. J., & Tang, J. (2015). Probiotics in personal care products. Microbiology Discovery, 3(1), 5. https://doi.org/10.7243/2052-6180-3-5 Habeebuddin, M., Karnati, R. K., Shiroorkar, P. N., Nagaraja, S., Asdaq, S. M. B., Anwer, M. K., & Fattepur, S. (2022). Topical Probiotics: More Than a Skin Deep. In Pharmaceutics (Vol. 14, Issue 3). MDPI. https://doi.org/10.3390/pharmaceutics14030557 Boxberger, M., Cenizo, V., Cassir, N., & la Scola, B. (2021). Challenges in exploring and manipulating the human skin microbiome. In Microbiome (Vol. 9, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s40168-021-01062-5 Sivamaruthi, B. S., Kesika, P., & Chaiyasut, C. (2018). A review on anti-aging properties of probiotics. In International Journal of Applied Pharmaceutics (Vol. 10, Issue 5, pp. 23–27). Innovare Academics Sciences Pvt. Ltd. https://doi.org/10.22159/ijap.2018v10i5.28249 Sfriso, R., Egert, M., Gempeler, M., Voegeli, R., & Campiche, R. (2020).

Revealing the secret life of skin - with the microbiome you never walk alone. In International Journal of Cosmetic Science (Vol. 42, Issue 2, pp. 116–126). Blackwell Publishing Ltd. https://doi.org/10.1111/ics.12594

Nutramedic &Cosmetics

Vita Nova professional services offering raw materials and application

T

he beginnings of the company Vita Nova date back to 2006, when the first office and official representation of respectable foreign pro­ ducers of the highest quality raw materials intended for the pharmaceutical, cosmetic, food and other in­ dustries was opened in Skopje. Driven by the desire to offer quality raw materials to producers from the region, Vita Nova expanded its operations in 2008 by opening another office based in Belgrade, enabling companies from the region to deliver raw materials quickly and on time.

We offer: minerals and mineral salts, vitamins and vitamin premixes, emulsifiers, aromas, stabilizers, en­ zymes, hydrocolloids, lanolin, sweeteners and plant extracts. The Vita Nova team consists of responsible and ambitious food technologists, engineers, nutri­ tionists and pharmacists who, together with col­ leagues from logistics and finance, provide our cli­ ents with top-notch and professional service in the offer and application of raw materials, from the idea to the realization of the final product.

Through successful cooperation with foreign par­t­­ ners, Vita Nova provides its clients with continuous support and additional education through seminars and training. Each client enjoys an individual appro­ach, with the aim of recognizing their specific needs and expectations, so that we implement our knowledge and ideas in the form of a quality final product.

After 16 years of doing business with the countri­ es of the central Balkans, we can be proud of a large number of realized projects in the food, pharmaceu­ tical and cosmetic industries.

We look forward to new challenges and the reali­ zation of new ideas from our clients. For all your ideas and projects, contact us via the contact form on our website. Because we would like to grow together with you...

www.vitanova.com.mk/ www.linkedin.com/company/2966991/

Pycnogenol® and ADHD

confirmation of effectiveness without harmful side effects

A

new study delivers promising findings for parents and caregivers seeking a natural alternative to manage pediatric Attention-Deficit Hyperactivity Disorder (ADHD) behavior. Researchers found the super-antioxidant Pyc­ nogenol® French maritime pine bark extract may be effective in managing hyper­ activity and impulsivity in children aged six to twelve, without many of the ad­ verse side effects experienced with the common therapy of methylphenidate, a prescription stimulant.

“ADHD is a perplexing condition and treatment can be frustrating for many parents and children. Parents often feel reluctant to continue with prescription pharmaceuticals due to common side effects.” says author and renowned natural physician, Dr. Fred Pescatore. “Management of ADHD behavior is pivotal to im­ proved school performance and self-esteem, especially during a child’s forma­ tive years. This study suggests a promising natural path option.”

The study, published in the Journal of Functional Foods, tested 88 children for ten weeks. Participants were split into three groups: placebo, methylphenidate and Pycnogenol®. The children supplemented at breakfast with either one or two capsules, depending on their weight. Those under 66 pounds supplemented with 20 mg/day of Medikinet® (methylphenidate) or 20 mg/day of Pycnogenol®. Those 66 pounds or heavier supplemented with 30 mg/day of Medikinet® or 40 mg/day of Pycnogenol®.

Teachers and parents filled out various questionnaires at baseline and after five and ten weeks, including the ADHD Rating Scale (ADHD-RS), which assesses nine inattention and nine hyperactivity/impulsivity items. Some of the criteria as­ sessed included difficulty following instructions, difficulty organizing tasks and activities, fidgeting with hands or feet or squirming in seat and interrupting or in­ truding others.

After ten weeks, teachers reported the Pycnogenol® group showed: • 29% decrease in overall ADHD rating scale (vs. 45% decrease with methylphe­ nidate vs. 5% decrease with placebo) • 34% decrease in hyperactivity/impulsivity (vs. 36% decrease with methylpheni­ date vs. 1% increase with placebo) • 25% decrease in inattention (vs. 52% decrease with methylphenidate vs. 9% decrease with placebo)

After ten weeks, parents reported the Pycnogenol® group showed: • 11% decrease in overall ADHD rating scale (vs. 28% decrease with methylpheni­ date vs. 1% increase with placebo) • 12% decrease in hyperactivity/impulsivity (vs. 28% decrease with methylpheni­ date vs. 2% increase with placebo) • 0% decrease in inattention (vs. 29% decrease with methylphenidate vs. 1% in­ crease with placebo) Children in the study who supplemented with the pharmaceutical showed im­ provement in ADHD behavior yet experienced up to five times more adverse ef­ fects than those who supplemented with Pycnogenol®. Specifically, loss of appe­ tite and unwanted weight loss was observed with the pharmaceutical, but not with Pycnogenol®. The researchers conclude, “In pediatric ADHD and especially in the primary school environment, Pycnogenol® was proven to be a good alterna­ tive for methylphenidate for those willing to wait a few weeks for effects, a for­ tiori when considering its almost complete lack of adverse effects as opposed to methylphenidate.”

This research expands Pycnogenol®’s deep catalog of clinical research for cog­ nitive support, solidifying the natural ingredient’s ability to manage ADHD behav­ ior without disruptive side effects. A 2006 study conducted in the Department of Child Psychiatry at the University Hospital in Bratislava found that Pycnogenol® relieved hyperactivity and improved attention of children with ADHD compared to placebo. Another study, conducted in 2006, found Pycnogenol® normalizes to­ tal antioxidant status of ADHD children.

To review clinical research and additional information on Pycnogenol®, visit www.pycnogenol.com.

39

Nutramedic &Cosmetics

Probiotics lysates in skin care

Current European regulation limits the number of microorganisms that a cosmetic formulation can contain, and therefore they are replaced by lysates. We are introducing three innovative and high-performance active cosmetic components based on Lactococcus lactis lysate and bifidobacteria lysate whose effect is identical to that of a healthy microbiome on general skin health.

AUTHOR:

Maja Pavlić, Industry Sales Manager, Fagron Hrvatska d.o.o.

40

1. INTRODUCTION

T

he application of probiotics in cosmetics is a re­ lative novelty and unique way of skin care by sti­ mulating skins natural ability to regenerate, more pre­ cisely by helping to maintain the balance of the mi­ crobiome. The skin microbiome consists mainly of bac­ teria, viruses, fungi, archaea and microeucariotes. The exact composition and amount of microbes on the skin depends on individuals and their health and age status, and gender. The stability and function of skins microbiome, in addition to the host factor, is also in­ fluenced by the interactions between the microor­ ganisms themselves. They can act “synergistically” and favorably, or "competitively" to exclude each other. The microbiological imbalance of the skin, just like the one inside the organism, can lead to the development and progression of certain skin diseases. Equ­al­ly re­ sident microbes, that is, permanent "inhabitants" of the skin, can help activate the body's immune res­po­n­ se and thus prevent infection.

Probiotic bacteria live on epithelial cells and are identical to the microflora of the skin. Epithelial cells and probiotic bacteria live in mutual symbiosis.

The result of a collaboration between epithelial cells and probiotic bacteria on the skin is remarkably

similar to that of the intestinal microflora. The pres­ ence of probiotic bacteria on the skin prevents colo­ nization of pathogenic bacteria, enhances the func­ tion of the epithelial barrier, increases the produc­ tion of antimicrobial peptides and strengthens the immune system. Successful epidermal differentia­ tion leads to a healthy skin flora, when the skin and its microbiome are in perfect harmony.

FIGURE 1 Collaboration between epithelial cells and probiotic bacteria

Nutramedic &Cosmetics FIGURE 2 The relationship between the skin

and the microbiome

An unhealthy microbiome always contributes to the incomplete functioning of the skin, while a heal­thy microbiome makes an essential contribution to the dif­­ferentiation of the epidermis as well as the processes of renewal. Ultimately, we get a positive feed­ back loop: the skin microbiome benefits from the functi­o­­nal processes of epidermal skin renewal, but also the­se processes, for their part, benefit from the microbio­me of healthy skin. It is a positive vici­ ous circle - sym­biosis.

Antimicrobial peptides collaborate with the "good" bacteria that live on our skin, to ensure that the skin does not become colonized by "bad" bacteria. "Good" bacteria have a positive effect on skin renewal pro­ cesses by boosting its ability to manage its microbio­ me even better. "Good" bacteria cooperate with AMP (adenosine monophosphate) produced by keratino­ cytes in the fight against pathogens.

FIGURE 3 Probiotics and keratinocytes in the

fight against pathogenic bacteria

FIGURE 4 Skin Microbiome in fight with UV radiation

is essentially an immune process. The skin under nor­ mal circumstances, immune-wise, is extremely acti­ ve. Immunosuppression caused by UV radiation is an extremely important topic in the context of skin ag­ ing. The accumulation of cellular damage is one of the key factors in the aging process of the skin. There­ fore, a fully functioning immune system is of para­ mount importance. Because of its immunosuppres­ sive effect, the anti-aging effect on the skin was at­ tributed to one of the active ingredients that will be introduced in more detail below.

CLR – Chemisches Laboratorium Dr. Kurt Richter GmbH - is a company that has been engaged in the development and production of innovative and high-­quality active cosmetic components for skin and hair care for 70 years. Due to its specialization in the production of biologically active products, skin care probiotics is a topic that CLR has been dealing with for more than 35 years.

The question that arises is how and which probio­ tic bacteria to use for treatment in the care of sick or troubled skin when the microbiome is in the imba­ lance. Probiotics are often called "good" microorgan­ isms, but they are still microorganisms. Current Eu­ ropean regulation limits the number of microorgan­ isms that the formulation can have, and therefore in cosmetics they are being replaced with lysates. Pro­ biotics lyzates are dead and lysed probiotic bacteria that contain molecules of probiotic bacteria and can interact with the same receptors on keratinocytes as they do on epithelial cells, for example in the gut. Be­ low we present three innovative and high-perfor­ mance active cosmetic components based on Lacto­ coccus ferment lysate (Prorenew Complex CLR) and Bifida ferment lysate (Repair Complex CLR and Pro­ BioBalance CLR) whose action in cosmetic formula­ tions is identical to the effect of a healthy skin mi­ crobiome on general skin health.

2. PRORENEW COMPLEX CLR™

The interaction between good skin bacteria and differentiating keratinocytes has many positive ef­ fects: the processes of skin renewal improve, which leads to a better functioning of the skin barrier, but also to increased production of AMP, that is, an im­ proved ability to manage its own microbiome. This provides a more favorable environment for the growth of good bacteria which can then interact with skin cells. In this context, a scientific publication pub­ lished in 2016 described that Staphylococcus epi­ dermidis (generally accepted as a good skin bacte­ ria) has effects on the skin "similar to probiotics".

Another interesting observation that was pub­ lished in the first half of 2017 is that the microbiome of healthy skin protects the skin from uv-induced immunosuppression.

UV radiation not only damages skin cells, but also prevents them from the regeneration process, which

P

roRenew Complex CLR™ acts on essential fea­ tures in the aging process of the skin, its ability to successfully adapt to a constantly changing envi­ ronment and to effectively renew itself.

INCI: Lactococcus ferment lysate Dosage: 3.0 % pH: 4.0 - 7.0 Solubility: Miscible with water and water-alcohol mixtures containing a maximum alcohol concentration of 50 % w/w.

Preservative: sodium benzoate* Also available as ProRenew Complex CLR™ NP, stabilized phenylpropanol and levulic acid/sodium levulinates

*

ProRenew Complex CLR™ positively influences the speed and quality of epidermal growth. It has shown to effectively promote desquamation, the shedding

41

Nutramedic &Cosmetics of dead cells. ProRenew Complex CLR™ is beneficial for both the health of skin and the skin microbiota. It balances and protects the skin microbiota and sup­ ports it in dealing with day-to-day stress. ProRenew Complex CLR™ also improves the condition of the scalp and makes it less oily. It additionally leads to perceiv­ able reduction of the sensitivity of the scalp, makes scalp tangibly healthier and reduces attributes rela­ ted to dryness of the scalp. ProRenew Complex CLR™ provides important support for the skin and the scalp, even from rinse-off formulations.

2.1 Activity

CLR has developed ProRenew Complex CLR™ (INCI: Lactococcus ferment lysate), based on a lysate of Lac­ tococcus lactis, to stimulate the skin’s self-renewal effectively. This probiotic lactic acid–producing bac­ terium is grown under specific conditions, after which the obtained cells are lyzed, a process involving the killing and destruction of the bacterial cells. Probiot­ ic bacteria are well-established in the food industry, and their benefits for the human body are described in many scientific, peer-reviewed papers. In the gut they beneficially influence the composition and me­ tabolic activity of the endogenous bacteria, and so­ me probiotic strains are even able to inhibit the growth of pathogenic bacteria. Probiotic bacteria are also reported to be able to modulate the immune system, essentially improving immunocompetence and, the­ re­fore, our body’s ability to adapt to negative influ­ ences. Interestingly, it is not the whole living probi­ otic bacterial cell which is needed for the latter ac­ tivity, it is the constituents and metabolites of these bacteria which are essential. A product obtained from a lysate of Lactococcus lactis, as ProRenew Complex CLR™, which essentially contains the cell debris of this bacterium – such as cell fragments, like DNA, me­ tabolites, cytoplasmic compounds, and cell wall ma­ terials – should show and, in the studies performed, has shown that it is able to improve both the skin re­ newal processes and the processes involved in the skin’s adaptation to negative influences.

2.2 Efficiency studies In vitro tests (cell culture tests) 2.2.1 Caspase-14

Caspase-14 is essential for the maintenance of

FIGURE 2.2.1 Caspase-14 expression with ProRenew Complex CLR™ is clearly

higher than control

42

normal and healthy keratinocyte differentiation, cornification, the architecture of the SC, and the for­ mation of the cornified envelope. Treatment of the growing epidermal skin model with ProRenew Com­ plex CLR™ (growth followed for 14 days, 3% ProRe­ new Complex CLR™ applied in medium) led to an acti­ vation in the production of caspase-14. Histological pictures were made (magnification 400x, Fig. 2.2.1).

2.2.2 The recovery of the skin barrier

The skin treated with ProRenew Complex CLR™ clearly showed an increased rate in the recovery of a healthy barrier function of the skin after tape strip­ ping (Fig. 2.2.2) FIGURE 2.2.2 Impact of ProRenew Complex CLR™

on skin barrier recovery

In vivo tests (on volunteers) 2.2.3 The impact on desquamation (peeling of the skin)

Eighteen volunteers applied a formulation conta­i­ ning 3% of Pro-Renew Complex CLR™ and correspon­ ding placebo on designated areas on the outer fore­ arms, twice daily for 42 days. On day 43 of the study, the gradient in cell cohesion in the stratum corneum was determined by tape stripping and quantifying pro­ tein mass on the strips obtained. Treatment with FIGURE 2.2.3 Impact on protein mass on strips

Nutramedic &Cosmetics ProRenew Complex CLR™ clearly leads to a more pro­ nounced gradient in protein mass, hence cell cohesi­ on, as compared to the skin treated with placebo, (Fig. 2.2.3). ProRenew Complex CLR™ promotes healthy de­squamation.

2.2.4 The acceleration of skin renewal

Test products were applied on designated skin ar­ eas on the inner forearm of 5 female volunteers (47– 63 years old) for 2 weeks, twice daily. After that, tape stripping was performed to remove stratum corne­ um and induce skin damage. By measuring the thick­ ness of the stratum corneum 1 hour, 2 and 4 days af­ ter tape stripping it was shown that the skin treated with ProRenew Complex CLR™ had a clearly acceler­ ated rate of skin renewal (Fig. 2.2.4).

FIGURE 2.2.4 Acceleration of skin renewal

3. REPAIR COMPLEX CLR™ PF

R

epair Complex CLR™ PF is a biotechnological an­ ti-aging active, obtained from a lysate of probi­ otic bifidobacteria, which potently protects against UV-induced damage in the skin. UV radiation leads to skin cell damage and immunosuppression, a deacti­ vation of the local immune system in the skin.

INCI: Bifida ferment lysate Dosage: 5.0 – 10.0% pH: 3.8 – 7.0 Solubility: Soluble in water.

Preservative: phenoxyethanol i sodium benzoate

By effectively activating anti-immunosuppressi­ ve processes on the cellular level, Repair Complex CLR™ PF increases cellular repair and potently sup­ ports the skin’s endogenous protection mecha­ nisms. Repair Complex CLR™ PF thus counteracts pre­mature skin aging, i.e. photoaging.

3.1 Efficiency studies In vitro tests (cell culture tests) 3.1.1 Protection from UV-induced immunosuppression

Depending on the dose, Repair Complex CLR™ PF reduces IL-10 release by more than 30% compared with control (Fig. 3.1.1).

2.3 ProRenew Complex CLR™ in cosmetic formulations

FIGURE 3.1.1 Reduction of IL-10 expression after

UV irradiation

ProRenew Complex CLR™ is a yellowish-beige, opa­ lescent suspension with characteristic weak odor.

ProRenew Complex CLR™ can be used in formulation concepts to accelerate the recovery of the skin's ba­ r­rier function, regardless of type of impairment (en­ vironmental stress, aging). It is miscible with water and water-alcohol mixtures containing a maximum alcohol concentration of 50% w/w, but yields no clear solutions. During the production process ProRenew Complex CLR™ should not be exposed to temperatu­ res exceeding 40 °C. The pH of final formulations co­n­ t­aining ProRenew Complex CLR™ should range bet­ ween 4 and 7. If stored at room temperature (15-25 °C), in well closed containers, protected from light, Pro­ Renew Complex CLR™ is stable for at least 1 year. Pro­ duct packs should be fully used once opened.

43

Nutramedic &Cosmetics 3.1.2 Protection against DNA damage

Severe UV exposure leads to the formation of non-repairable cells with DNA double-strand breaks, which initiates apoptotic processes. Cells going into apoptosis show the formation of micronuclei. Repair Complex CLR™ PF significantly reduces the amount of cells going into apoptosis, clearly illustrating its ability to induce DNA repair (Fig. 3.1.2).

FIGURE 3.1.2 Formation of micronucleus [%] after

UV irradiation in normal fibroblast cells

In vivo tests (on volunteers) 3.1.3 The proof of DNA repair stimulation

The intact dorsal skin of 7 volunteers was treated on 5 test areas in the following manner:

The area treated with Repair Complex CLR™ PF (A) showed an increase in DNA repair effectiveness in comparison with areas B and C. Without UV irradiati­ on, no repair process was induced (D and E) (Fig. 3.1.3).

FIGURE 3.1.3 Increasing DNA repair activity in vivo

4. PROBIOBALANCE CLR™ NP

P

roBioBalance CLR™ NP activates cellular proces­ ses involved in cellular nutrition and helps acti­ vate detoxification processes. The metabolic activi­ ty of skin cells is increased, and the skin’s immune system strengthened and protected against envi­ ronmental stress. The application of ProBioBalance CLR™ NP leads to reduction of skin inflammation and also actively prepares skin for external stresses.

INCI: Water, Lactose, Milk protein, Bifida ferment lysate Dosage: 2.0 – 5.0% pH: 5.8 – 7.0 Solubility: Soluble in water.

Konzervans: phenethyl alcohol

ProBioBalance CLR™ NP activates cellular process­ es involved in cellular nutrition and helps activate de­toxification processes. The metabolic activity of skin cells is increased, and the skin’s immune system strengthened and protected against environmental stress. The application of ProBioBalance CLR™ NP leads to reduction of skin inflammation and also ac­ tively prepares skin for external stresses.

ProBioBalance CLR™ NP consists of probiotic bifi­ dobacteria disintegrated in a bioactive milk-based nu­­­trient. It constitutes a complete approach toward probiotic nutrition for the skin. Nutritional cosmet­ ics are a large and strongly growing segment of the personal care market. Consumers understand the need of “feeding” the skin with beneficial ingredients from cosmetic skincare formulations. ProBioBalan­ ce CLR™ NP has a multiple approach to skin nutrition.

It provides the skin and the skin cells with essential nutrients from milk, enabling the digestion of the nutrients (Fig. 4.1.1). Yet it also contains another, revo­ lutionary approach toward skin nutrition. In essen­ce, especially in aged skin, the skin cells accumulate high amounts of defective and damaged cellular com­ ponents. The accumulation of this cellular “waste” is considered one of the hallmarks of aging. Interest­ ingly, ProBioBalance CLR™ NP is able to activate in­ tracellular systems, allowing for the disposal and re­ cycling of cellular waste, which essentially means that it can activate cellular detoxification systems and en­ ­­able the reuse of the waste. The endpoint of the ac­ tivation of these so called autophagy processes, du­ ring which cellular waste is “engulfed” by autophago­ somes, is similar to that of providing the cells with essential nutrients from milk – the cells become he­ althier and more vital (Fig. 4.1.1).

FIGURE 4.1.1 Inside the cellular processes of digestion

of nutrients and autophagy of cellular waste

44

Nutramedic &Cosmetics This dual approach to cellular nutrition with Pro­ BioBalance CLR™ NP illustrates its potency as a cos­ metic active ingredient for skincare formulations, but not just for nutritional cosmetics. It additionally strengthens the immune system, for instance, as would be expected from a product based on probio­ tic bacteria. This activity spectrum of ProBioBalance CLR™ NP was proven in vitro on skin cells and in vivo on human skin.

FIGURE 4.2.2 Negative influence of UV light on the immune system IL-10 immunosuppressor

4.2 Efficiency studies In vitro tests (cell culture tests) 4.2.1 Maintaining a balanced immune system

Interleukins are cytokines that act as signal mole­ cules of the immune system. These mediators are essential for the induction and complete process of immune reactions. Immunosuppression signifies the suppression of immune responses. Imunosup­ pressive action can be triggered by stress of any kind, especially excessive UV irradiation of the skin.

An immunological imbalance in the skin after UV ex­ posure has important implications not only for the exacerbation of infectious diseases but also for the generation of skin cancer. UV-induced modulation of immunoregulatory cytokines with upregulation of interleukin 10 (IL-10) and IL-12 downregulation are the critical events responsible for immunosuppres­ sion. Consequently, it is necessary to have a bal­ anced proportion between IL-12 and IL-10 in order to avoid a down-regulated immune system due to IL-10.

Keratinocytes and immunocompetent cells release Interleukin 10 (IL-10), the mediator responsible for immunosuppression. Keratinocytes pretreated with ProBioBalance CLR™ NP show reduced IL-10 expres­ sion after UV irradiation (Fig. 4.2.1 and Fig. 4.2.2). The active thus counteracts imbalances of the immune system.

4.2.2 Protection of extracellular matrix (ECM) - Impact on cathepsin B

Cathepsins are intracellular proteolytic enzymes involved in the final catabolism of predigested pro­ teins (for example, by matrix-metalloproteases, or MMPs). Cathepsin B represents a marker of cell dam­ age after UV exposure (Fig. 4). UV-irradiated kerati­ nocytes, pretreated with ProBioBalance CLR™ NP, showed reduced Cathepsin B activity (Fig. 5). ProBio­ Balance CLR™ NP counteracts the UV-induced de­ generation of collagen and elastin, thus maintaining homeostasis of the extracellular matrix composi­ tion.

FIGURE 4.2.3 Extracellular Matrix Protection (ECM)

FIGURE 4.2.1 Influence of IL-10 immunosuppressor

FIGURE 4.2.4 Release of Cathepsin B by keratinocytes after UV irradiation

45

Nutramedic &Cosmetics 4.2.3 Supply of nutrients - activity of lysosomes after cells malnutrition

Lysosomes are the digestive system of our cells. A battery of lysosomal enzymes digest food ingredi­ ents, macromolecules, and cellular debris. The more lysosomes are active, the better the cell is nurtured.

Keratinocytes were grown in a complete medium providing optimum nutrition with and without Pro­ BioBalance CLR™ NP. After 72 hours the complete medium as well as ProBioBalance CLR™ NP were re­ moved, and the concentration of nutritive substan­ ces was reduced to undernourish the cells. Under the conditions produced by the incomplete medium, the cells pretreated with ProBioBalance CLR™ NP re­ mained on a higher vitality level and could cope with stress situations without difficulties (Fig. 4.2.5 and Fig. 4.2.6).

FIGURE 4.2.7 Increase in autophagosome production and cellular waste disposal and reuse

FIGURE 4.2.5 increase in lysosome activity after cells malnutrition

4.2.5 The increase in metabolic activity of cells

A seemingly logical consequence of cellular nutri­ tion – whether by supplying nutritive elements or activating cellular waste disposal and reuse – is that the skin cells become more vital and show higher levels of activity. This is indeed the case with ProBio­ Balance CLR™ NP. In an MTT assay, a colorimetric as­ say where the activity of NAD(P)H-dependent oxi­ doreductase enzymes is quantified, the metabolic activity of cells, which allows them to grow and re­ produce, was determined. The metabolic activity of cells was increased depending on the concentration of ProBioBalance CLR™ NP (Fig. 4.2.8).

FIGURE 4.2.8 Povećanje stanične metaboličke

aktivnosti FIGURE 4.2.6 supply of nutrient elements

4.2.4 Activating the disposal and recycling of cellular waste

Cellular waste can be disposed of and made avail­ able for reuse by autophagy. During this process, cellular waste is captured in autophagosomes. The autophagosomes then fuse with lysosomes, allow­ ing for the digestion of the cellular waste. The outer cell membrane of autophagosomes contains a uni­ que protein called LC3B, which serves as a general marker for autophagic membranes and for monitor­ ing autophagosome production as they develop.

Cells were grown in the presence of ProBioBalance CLR™ NP. At different concentrations, ProBioBalance CLR™ NP shows an increase in LC3B (Fig. 4.2.7), lead­ ing to the conclusion that it induces autophago­ some production and, therefore, cellular waste dis­ posal and reuse.

46

Nutramedic &Cosmetics 4.2.6 In vivo tests (on volunteers)

Day after day, our whole body is exposed to both environmental stress and the strains of everyday life. Under stress conditions, we are more short-tem­ pered, our immune system deteriorates, and our skin becomes more sensitive, easily irritated, and thus vulnerable. ProBioBalance CLR™ NP acts as a protec­ tive shield for the skin. It helps reduce irritability of the skin and at the same time protects it from addi­ tional stress. The less the skin is irritated, the more balanced it is. ProBioBalance CLR™ NP leads to a more balanced skin, as could be demonstrated in vivo in 20 volunteers: Defined skin areas were treat­ ed with SDS to induce redness (irritation). Decrease in redness was then recorded for skin areas treated twice daily with a formulation containing 5% ProBio­ Balance CLR™ NP and compared with placebo and untreated controls. On Day 9 the SDS treatment was repeated and the development of skin redness re­ corded. An O/W cream with 5% ProBioBalance CLR™ NP was shown to reduce the visible signs of skin irri­ tation, and the skin was much better protected against skin damage compared to untreated and placebo (Fig. 4.2.9).

References: Internet sources: 1

Books: 1

Zsuzsanna Bösze (editor): Springer Science and Business Media, LLC (2008): Advances in Experimental Medicine and Biology, Volume 606, Bioactive components of milk.

2

J. Krutmann: J. Dermatol Sci, 54 (2009), 1–5. Pre- and probiotics for human skin.

3

T. Volz, T. Biedermann: Hautarzt, 60 (2009), 795–801. Outside-in, Probiotische Externa.

4

A.M. Cuervo, E. Bergamini, U.T. Brunk, W. Dröge, M. Ffrench, A. Terman: Autophagy, 1:3 (2005), 131–140.: Autophagy and aging The importance of maintaining “clean” cells.

5

T. Nakatsuji, R.L. Gallo: J. Invest Dermatol, 134 (2014), 11–14.: Dermato­ logical therapy by topical application of non-pathogenic bacteria.

6

I.H. Kuo, A. Carpenter-Mendini, T. Yoshida, L.Y. McGirt, A.I. Ivanov, K.C. Barnes, R.L. Gallo, A.W. Borkowski, K. Yamasaki, D.Y. Leung, S.N. Georas, A. De Benedetto, L.A. Beck: Journal of Investigative Dermatology 133 (2013), 988–998.: Activation of Epidermal Toll-Like Receptor 2 Enhances Tight Junction Function: Implications for Atopic Dermatitis and Skin Barrier Repair.

7

M.A. Lefebvre, D.M. Pham, B. Boussouira, D. Bernard, C. Camus, Q.L. Nguyen: Int. J. Cosmetic Sci., 37 (2015), 329–338.: Evaluation of the impact of urban pollution on the quality of skin: a multicentre study in Mexico.

8

M. Rinnerthaler, J. Duschl, P. Steinbacher, M. Salzmann, J. Bischof, M. Schuller, H. Wimmer, T. Peer, J.W. Bauer, K. Richter: Exp. Dermatol., 22 (2013), 329–335.: Age-related changes in the composition of the cornified envelope in human skin.

9

S.J. Brown, W.H. Irwin McLean: J. Invest. Dermatol., 132 (2012), 751–762.: One remarkable molecule: filaggrin.

10

E. Hoste, P. Kemperman, M. Devos, G. Denecker, S. Kezic, N. Yau, B. Gilbert, S. Lippens, P. De Groote, R. Roelandt, P. Van Damme, K. Gevaert, R.B. Presland, H. Takahara, G. Puppels, P. Caspers, P. Vandenabeele, W. Declercq: J. Invest. Dermatol., 131 (2011), 2233–2241.: Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin.

11

A. Alikhan, H.I. Maibach: Textbook of aging skin, Edited by MA Farage et al., Springer Verlag, Berlin, Heidelberg, Germany (2010), Chapter 40. Biology of Stratum Corneum: Tape Stripping and Protein Quantification.

12

K.M. Aberg, M.Q. Man, R.L. Gallo, T. Ganz, D. Crumrine, B.E. Brown, E.H. Choi, D.K. Kim, J.M. Schröder, K.R. Feingold, P.M. Elias: J. Invest.

Dermatol., 128 (2008), 917–925.: Co-regulation and interdepen­ dence of the mammalian epidermal permeability and antimicro­ bial barriers.

13

R. Ghadially, B.E. Brown, S.M. Sequeira-Martin, K.R. Feingold, P.M. Elias: J. Clin. Invest., 95 (1995), 2281–2290.: The aged epidermal permeability barrier.

FIGURE 4.2.9 Reducing skin irritation and

protection

Križanović M. (2021): Primjena probiotika u očuvanju zdravlja kože, Sveučilište u Zagrebu, Farmaceutsko-biokemijski fakultet, Zavod za kemiju prehrane. Preuzeto s: https://urn.nsk.hr/ urn:nbn:hr:163:570217

4.3 ProBioBalance CLR™ NP in cosmetic formulations

ProBioBalance CLR™ NP as a cosmetic active will mainly be used in leave-on formulations such as creams, lotions, milks and different gel forms. The recommended use level is between 2–5%. No incom­ patibilities with the different emulsifier families, such as anionic or silicone emulsifiers, are known.

Clear gels can be formulated without any difficul­ ties. The use of alcohol in water-based formulations should not exceed 20% w/w. The pH range of the for­ mulations with ProBioBalanceCLR™ NP should be ad­ justed to 5.8–7.0. ProBioBalance CLR™ NP should be added during the cooling process, when the tem­ perature is below 40°C. Homogenization does not influence the activity of the cosmetic active.

CLR Chemisches Laboratorium Dr. Kurt Richter GmbH

Fagron Hrvatska d.o.o.

Donjozelinska 114 10382 Donja Zelina, Hrvatska info@fagron.hr T +385 1 2043 322

47

Nutramedic &Cosmetics

Let’s meet in Paris!

Leading ingredients trade show Fi & Hi Europe all set to welcome more than 20,000 visitors from around the world Fi & Hi Europe returns to France this year.

F

rom December 6 to 8, the leading ingredients fair will be held for the first time at the Paris Expo Porte de Versailles exhibition centre.

More than 1,200 exhibitors – from leading ingredi­ ents manufacturers to highly specialized startups – will present themselves in four halls. The face-toface exhibition will be complemented by a compre­ hensive online offering. A broad conference pro­ gramme, as well as the renowned Innovation Awards and Startup Innovation Challenge, will complete the trade show experience.

In the heart of Paris, Fi & Hi Europe is set to attract exhibitors and attendees from more than 135 coun­ tries around the world. The new Paris Expo Porte de Versailles location is within walking distance of many hotels, restaurants and bars, making logistics easier and the event more visitor-friendly than ever before.

Digitally enabled event concept

This year, Informa Markets is focusing on a tech­ nologically enhanced hybrid show concept. The combination of online and face-to-face events of­ fers participants the best of both worlds, including a wide variety of live and on-demand content as well as data-driven networking options. All exhibiting com­panies have their own online profile, allowing them to find relevant contacts, network and set up virtual or face-toface meetings before the event. A smartphone app also facilitates on-site lead genera­ tion.

Multifaceted conference programme

The online event will begin on 28 November, the week before doors open at Paris Expo Porte de Ver­ sailles. It offers an extensive conference programme covering the hottest topics in the industry, with a fo­ cus on plant-based nutrition, health & wellness, and reformulation. In addition, interested participants will find a wealth of information on application ar­ eas that are currently trending – such as baked goods, snacks, dairy products and dairy alternatives.

Overall, the conference programme includes more than 55 expert sessions on-site and online, giving global audiences access to invaluable knowledge.

Market products in the spotlight

On-site, the New Product Zone in cooperation with Innova Market Insights offers an extensive se­ lection of the most innovative products, showcased alongside insightful information. It features product innovations from leading industry players and pro­ vides the perfect opportunity to give new ingredi­ ents the introduction to the market that they de­ serve. A popular area for visitors and the press, this feature has become a trendsetting spot for the nu­ trition industry.

48

Fi Europe Innovation Awards

The renowned Fi Europe Innovation Awards will once again be adding extra value to the trade show.

With one exception, the awards will only be present­ ed among Fi Europe exhibitors.

Award for innovative startups

The Fi Global Startup Innovation Challenge also enables young companies to present their innova­ tive concepts, products and ideas to an internatio­nal audience of experts, major companies and sponsors.

All companies founded no more than five years ago are eligible to participate.

In addition to the Innovation Hub, visitors will find the new Sustainability Hub at the exhibition, which focuses on sustainable food solutions along the en­ tire value chain. Here visitors will find information on food waste, circular economy, regenerative agri­ culture and many other topics. Finally, the Women’s Networking Breakfast, sponsored by DSM, Lunch & Learn and other events are perfect for building a professional network.

More information about the show can be found at: www.figlobal.com/fieurope/en/home.html

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Nutramedic &Cosmetics

Biofach Congress 2023 During the next edition of the world's leading organic food fair, from 14-17 February 2023, a congress focusing on organic production, food sovereign and true prices will be held.

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or the next edition of the World’s Leading Tra­ de Fair for Organic Food, from 14 to 17 Febru­ ary 2023, the BIOFACH Congress will be focus­ sing on “Organic. Food Sovereignty. True Prices.” Fol­ lowing the one-off Summer Edition of BIOFACH and VIVANESS in July 2022, in February 2023 the interna­ tional organic foods and natural and organic cosme­ tics community will be gathering again in person to kick off the year at the Nuremberg Exhibition Cen­ tre. The BIOFACH Congress will be concentrating on two key questions: How do organic products con­ tribute to food security and sovereignty, and how do “true prices” – prices that include ecological after­costs – pave the path for the necessary transforma­ tion of the food and grocery industry?

“To expand organics’ contribution to sustainability further, and thus for the transformation of the food industry as a whole to succeed, the market’s failure at using environmental resources must be put to an end at last. Only ‘true prices’ will make it possible to do business within the bounds our planet can sup­ port, leading to the success of a food and agriculture industry that is truly fit to serve our grandchildren.

International organisations and government must ma­ ke the most of organics’ potential”, said Tina Andres, Chairwoman of the Federation of the Organic Food Industry (BÖLW).

“Current food pricing takes the ‘polluter pays’ prin­ ciple and turns it upside down, making environmen­ tally harmful products look ‘cheaper’ than they really are. So organic foods that present more honest cos­ ting are at a disadvantage. Which means that thus far, you can make a profit by doing business convention­

ally – even though it undermines the foundations of life for coming generations. The great market failure in food must be remedied with new systems for acco­ unting, taxation and support. At the congress we want to discuss just how that might be done”, Andres added.

Marco Schlüter, Executive Director, IFOAM – Orga­ nics International: “Organic practices have demons­ trated a clear ability to provide solutions and ensure a secure, sovereign food supply, because this sustai­ nable way of doing business reinforces farmers’ auto­ nomy and generates added value on a regional basis.

The organic system’s contributions towards strengt­h­ ening a secure, sovereign food supply in every regi­ on of the world will also be discussed at the 2023 BIOFACH Congress in light of the current crises.”

Food: Sovereign and secure

The rising prices of energy and food show how fa­ tal it is to depend on fossil fuel-based fertilisers.

Meat production in the global north is not tailored to available grazing area, and also contributes to the rise of hunger in the south – which is why we must begin raising livestock on the basis of the space that’s available. Planting coffee or cacao in agrofor­ estry systems demonstrates how much potential or­ ganic techniques have to offer in actively protecting the climate. What’s more, supply chains that are overlong, and thus especially vulnerable to disruption in times of crisis, prove how important it is to have sta­ ble, regional value chains.

True prices can remedy market failures and facilitate transformation

Ninety billion euros a year* – agriculture in Germa­ ny causes that much damage to the general good that is not reflected in the price of food. That was the re­ sult of a study by the Boston Consulting Group (BCG) and the concluding report of the Commission on the Future of Agriculture (ZKL) of Germany’s Federal Mi­ nistry of Food and Agriculture (BMEL). The cost is ma­ ny times the sector’s value added. The organic food industry can avoid doing most of this damage beca­ u­se it does business in a way that protects resources.

The disruptions caused by the COVID-19 crisis, the impact of the war on Ukraine, the energy crisis, the consequences of the climate crisis and species ex­ tinction – these are ratchetting up social and econo­ mic tensions around the globe. But organic products make the food supply more secure, thanks to their closed-loop economy, lower dependence on exter­ nal inputs, and strong regional value chains. By ope­ rating in a way that conserves resources, organic practices reinforce biodiversity, enhance soil fertili­ ty, and protect the climate, yielding resilient crop­ ping systems and food sovereignty.

Find out more about the Congress at: www.biofach.de/en/biofach-congress

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