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The Future of Personalized Lifestyle Medicine: Application to the Clinic Deanna Minich, PhD, FACN, CNS Vice President, Education

www.plminstitute.org


Outline • Origins of personalization in healthcare • 21st century health trends • Merging the medical worlds • Personalized medicine • Personalized lifestyle medicine (PLM) • PLM protocols


Health is personal.


“It’s far more important to know what person has a disease than what disease a person has.” - Hippocrates


The origins of personalized healthcare come from traditional medical systems.


Traditional Medicine Systems are built upon personalization.


“Although the concept of personalized medicine is new to modern medicine, it is a wellestablished concept in Ayurveda, the traditional system of Indian medicine that is still being practiced.�

J Altern Complement Med. 2013 Apr;19(4):370-5. doi: 10.1089/acm.2011.0698. Epub 2012 Oct 25.


Ayurveda & Personalized Medicine

“Every individual is different from another and hence should be considered as a different entity. As many variations are there in the universe, all are seen in human beings.� - Charaka Samhita

Ayu. 2011 Apr;32(2):141-6. doi: 10.4103/0974-8520.92539. Prakriti-based medicine: A step towards personalized medicine. Chatterjee B, Pancholi J

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Ayurvedic Medicine • Five elements within the body and environment • Ayurveda has 8 ways of diagnosis. They are Nadi (Pulse), Mootra (Urine), Mala (Stool), Jinvha (Tongue), Shabda (Speech), Sparsha (Touch), Druk (Vision), Aakruti (Appearance). • Body type classification • Dietary prescriptions • Nadis corresponding to endocrine glands • Herbs


Ayurveda humors


J Transl Med. 2008 Sep 9;6:48. doi: 10.1186/1479-5876-6-48. Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda. Prasher B, Negi S, Aggarwal S, Mandal AK, Sethi TP, Deshmukh SR, Purohit SG, Sengupta S, Khanna S, Mohammad F, Garg G, Brahmachari SK; Indian Genome Variation Consortium, Mukerji M.


Traditional Chinese Medicine


Traditional Chinese Medicine


Traditional Chinese Medicine • Pulse diagnosis • Tongue diagnosis • Meridians and acupuncture • 5-element philosophy • Herbal decoctions


Not all symptoms are treated similarly in every individual Insomnia may have multiple causes in TCM: • Heart fire • Yin deficiency • Blood deficiency • Liver fire


“TCM focuses on health maintenance, emphasizes on enhancing the body's resistance to diseases and especially shows great advantages in early intervention, personalized and combination therapies, etc.�

Zhang et al. Complementary Therapies in Medicine Volume 20, Issue 1 , Pages 93-99, February 2012


Western Medicine: Physical Diagnosis


Body Weight


Body Weight Classifications Normal BMI 18.5-24.9

Overweight BMI 25-29.9

Obese BMI 30-40

Morbidly Obese BMI 40-50

SuperMorbid Obesity BMI >50


Firstline therapy


Male

Female

Health Risk Based Solely on WHR

= or < 0.90

= or < 0.80

Low Risk

0.90 to 1.0

0.81 to 0.85

Moderate Risk

>1.0

>0.85

High Risk


General Indicators of Nutritional Status

• Skin • Eyes • Hair • Nails • Lips/mouth • Teeth


Acne: Zinc Vitamin A Essential Fatty Acids Selenium Consider Food Allergy (eliminate refined foods and sugars)


Follicular Hyperkeratosis: Zinc Vitamin A Essential Fatty Acids Pancreatic enzymes B vitamins


Angular stomatitis: Riboflavin (Vit B2) Niacin (Vit B3) Pyridoxine (Vitamin B6)


Beauâ&#x20AC;&#x2122;s Lines Associated with severe illness, shock Low calcium White pitting â&#x20AC;&#x201C; Zinc deficiency

Thin, brittle nails: Correlated with low bone mineral density Low EFAs, Ca, Zn, Cu, protein, underfunctioning stomach (low acid, pepsin)


Poor night vision/glare: Vitamin A deficiency Zinc deficiency Low lutein and zeaxanthin


Functional Medicine


Functional Medicine Personalized biochemical and genetic approach to patient care


??

In the Functional Medicine model, the patient’s full story is of central importance

• Where does the symptom come from? • That is, what are the antecedents and triggers?

• What keeps it going? • That is, what are the mediators?

• And what can be done to change that dis-eased allostatic balance point the patient is locked into? • That is, what are the underlying points of leverage where intervention can be most effective?


Philosophy of Functional Medicine • Biochemical individuality based on genetic and environmental uniqueness • Patient centered versus disease centered • Dynamic balance of internal and external factors • Web-like interconnections of physiological factors • Health as a positive vitality – not merely the absence of disease • Promotion of organ reserve – healthspan


Functional Medicine


What has emerged in healthcare in the 21st century?


Are we looking at a global shift in health towards personalization utilizing developments in science and technology?


The 21st century as the age of personalization in modern healthcare? • Genome decoded at the turn of the century • Emergence of point-of-care diagnostics • Deconstruction of molecular pathways • Advances in technology


Medicine is least personal now. â&#x20AC;&#x153;Experts point to the irony that, at the dawn of an age of personalized medicine, the doctor-patient relationship is at its least personal. Doctors are paid by the number of patients they see, not for the time they invest in a personalized health maintenance regime or for health outcomes.â&#x20AC;?

Rick Mullin, Personalized Medicine, www.cen-online.org, February 2008.


“There are pessimists who see personalized medicine as nothing but words. But people don’t understand they are in the middle of a revolution until it’s over.”

David Parkinson, CEO for Nodality


What is personalized medicine? The practice of tailoring therapies to the specific genetic profiles of patients and their diseased cells.


â&#x20AC;&#x153;With the potential to transform medical practice across global communities, personalized medicine is emerging as the flagship of modern medicine.â&#x20AC;?

Zhang et al. Complementary Therapies in Medicine Volume 20, Issue 1 , Pages 93-99, February 2012


â&#x20AC;&#x153;Application of personalized medicine paradigms aims to achieve the right diagnosis and right treatment for the right patient at the right time at the right cost.â&#x20AC;?

Zhang et al. Complementary Therapies in Medicine Volume 20, Issue 1 , Pages 93-99, February 2012


Personalized Medicine Growth Drivers Treatment cost savings

Early detection

Patient compliance

Optimization of therapies

Drug safety

Myshk D. Creating a Personalized Medicine Strategy. PharmaVoice, May 2011


Have we reached the tipping point for personalized medicine? • Advances in technology • Dropping price points • Increased knowledge of biology & molecular basis of disease • Healthcare reform • Shift from volume-based business model to value-based business model • Upswing in adoption of molecular diagnostics by physicians and their acceptance by payers.

Myshk D. Creating a Personalized Medicine Strategy. PharmaVoice, May 2011


P4 Systems Medicine • Predictive • Preventive • Personalized • Participatory

“P4 medicine uses scientific, organizational and wellness strategies so that patients can access personalized medicine, thereby reducing the cost of healthcare.”

Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


P4 Systems Medicine â&#x20AC;&#x153;Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual.â&#x20AC;?

Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


P4 Systems Medicine â&#x20AC;&#x153;P4 medicine will be able to detect and treat perturbations in healthy individuals long before disease symptoms appear, thus optimizing the wellness of individuals and avoiding disease.â&#x20AC;?

Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


P4 Systems Medicine P4 medicine will 1) improve health care 2) reduce the cost of health care, and 3) stimulate innovation and new company creation.

Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


P4 Systems Medicine Many other challenges plaguing our planet, such as energy, environment, nutrition, and agriculture can be transformed by using such an integrated and systems-driven approach.

Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


Itâ&#x20AC;&#x2DC;s up to you. â&#x20AC;&#x153;Personalized medicine needs to be integrated into clinical practice, to enhance diagnosis, prognosis, and prediction of disease.â&#x20AC;?

Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


Public Health Genomics Initiative by CDC


http://www.cdc.gov/genomics/


http://www.cdc.gov/genomics/


As part of the 5-year plan • Licensure of genetic counselors • Reimbursable services for genetic counselors • Information gathering into electronic medical records to facilitate surveillance • Screening and fact sheets • Engage communities • Track genetic diagnosis, prevention, intervention across populations http://www.cdc.gov/genomics/


Personalizing health care: feasibility and future implications.

â&#x20AC;&#x153;Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.â&#x20AC;?


It’s already happening. “The public is not waiting. Awareness of personalized medicine is increasing with the rise in news coverage of technologies for early cancer detection and determining genetic propensities for disease. Do-it-yourself genetic testing kits are now available, and private companies offer routine screening.” Rick Mullin, Personalized Medicine, www.cen-online.org, February 2008.


Levels of personalized health Typing

Methylation

Standard Labs

Genetics

SNPs

Epigenetics

Phosphorylation

Biochemical

Functional Biomarkers


Genetic Testing is readily available to the consumer. “Navigenics – genomic testing service in Redwood Shores, CA, charges $2500 for an initial genetic scan and counseling session; $250 per year for its customers, for follow-up scans.”

Rick Mullin, Personalized Medicine, www.cen-online.org, February 2008.


Oncology has made the biggest strides. Genomic and transcriptomic technologies make the analysis of gene expression signatures and mutation status possible so that tumors may be classified more accurately with respect to diagnosis and prognosis. Am J Pathol. 2013 Aug 3. pii: S0002-9440(13)00468-9. doi: 10.1016/j.ajpath.2013.07.002. [Epub ahead of print]


“Ten years from now, looking at disease at the molecular level will be the way medicine is practiced. This is how oncology is viewed now. Oncologists currently look to segment different types of cancer. For example, breast cancer isn’t one disease; it’s a multitude of diseases.”

Myshk D. Creating a Personalized Medicine Strategy. PharmaVoice, May 2011


Examples of personalized medicine in oncology Genentechâ&#x20AC;&#x2122;s Herceptin for HER2 breast cancer Novartis Pharmaceuticalsâ&#x20AC;&#x2122; Gleevec for lung cancer


Companion Diagnostics â&#x20AC;&#x153;Companion diagnosticsâ&#x20AC;? is becoming a more profitable approach. Over the next ten years, it has been estimated personalized medicine will grow to 510% of the entire pharmaceuticals market. Several companies are already establishing diagnostic divisions to identify new biomarkers and meet the related diagnostic needs in-house by combining drug development with the production of the related diagnostic test.â&#x20AC;? Kalia M. Personalized oncology: Recent advances and future challenges. Metabolism Clinical and Experimental 62 (2013):S11S14.


There has been an evolutionary shift in medicine. “PWC estimates that the core personalized medicine market alone – comprised primarily of diagnostic tests and targeted therapies – accounts for $24 billion in sales and will grow 10% annually to $42 billion by 2015.”

Myshk D. Creating a Personalized Medicine Strategy. PharmaVoice, May 2011


â&#x20AC;&#x153;According to its new research report Personalized Medicine Market Analysis, the U.S. market for personalized medicine is anticipated to grow at a CAGR of around 12% during 2009-2015.â&#x20AC;?

Myshk D. Creating a Personalized Medicine Strategy. PharmaVoice, May 2011


Challenges • Identifying the right biomarkers • Conducting clinical trials with smaller patient populations • Managing co-approval pathways of companion diagnostic/therapeutic offerings • Optimizing value propositions for sophisticated payers and benefit managers. • Understanding the basic biology of the disease and drug target at the preclinical stage. Myshk D. Creating a Personalized Medicine Strategy. PharmaVoice, May 2011


21st Century Healthcare Concepts • Emergence • Systems Biology • Network Medicine • E-health • Virtual coaches • Telemedicine • Health Apps


The World of E-Health http://www.dfrobot.com/community/e-health-sensor-platform.html


Definition of E-health is debated. • Electronic health records • E-Prescribing • Telemedicine • Consumer health informatics • Health knowledge management • Virtual healthcare teams • Mobile devices • Medical research grids • Healthcare Information Systems 9/4/13

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E-health 10 factors for successful implementation of personalized e-health services: â&#x20AC;˘ Anxiety, trust, attitude toward using, computer self-efficacy, perceived system quality, search strategy, user's condition, health specific knowledge, Internet dependency and satisfaction with medical care.

Stud Health Technol Inform. 2013;192:965.


Telephone Coaching â&#x20AC;˘ 1756 papers, which was reduced to 30 after screening and relevance checks â&#x20AC;˘ Telephone coaching for people with chronic conditions can improve health behaviour, selfefficacy and health status. This is especially true for vulnerable populations who had difficulty accessing health services.

Aust Health Rev. 2013 Jun;37(3):381-8. doi: 10.1071/AH13005.


Health Apps

J Med Syst. 2013 Jun;37(3):9951. doi: 10.1007/s10916-013-9951-6. Epub 2013 May 12.


1eq


Telemedicine for obesity â&#x20AC;&#x153;When comparing patients who received more than one visit with either form of consultation, the TM group demonstrated substantially more improvement than the FTF group in improving nutrition (88% versus 65%), increasing activity (76% versus 49%), and decreasing screen time (33% versus 8%).â&#x20AC;? Telemed J E Health. 2013 Aug 27. [Epub ahead of print]


Teleneurohospitalist

Neurohospitalist. 2012 Oct;2(4):132-43. doi: 10.1177/1941874412450714.


Telemental health â&#x20AC;˘ Telemental health is effective for diagnosis and assessment across many populations (adult, child, geriatric, and ethnic) and for disorders in many settings (emergency, home health) and appears to be comparable to in-person care. â&#x20AC;˘ In addition, this review has identified new models of care (i.e., collaborative care, asynchronous, mobile) with equally positive outcomes.

Telemed J E Health. 2013 Jun;19(6):444-54. doi: 10.1089/tmj.2013.0075.


21st century technology is now merging with centuries-old traditional medicine


Ayurvedic constitution (prakruti) identifies risk factor of developing Parkinson's disease. The total mean score (Âąstandard deviation) for Vata was 11.0Âą3.9 in patients with PD and 6.9Âą3.0 in controls. This finding was significant (p<0.0001), indicating that the incidence of PD is highest in those with Vata Prakruti. J Altern Complement Med. 2013 Jul;19(7):644-9. doi: 10.1089/acm.2011.0809. Epub 2013 Mar 7.


Ayurgenomics

Ayu. 2011 Apr;32(2):141-6. doi: 10.4103/0974-8520.92539. Prakriti-based medicine: A step towards personalized medicine. Chatterjee B, Pancholi J.


Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation.

J Transl Med. 2008 Sep 9;6:48. doi: 10.1186/1479-5876-6-48.


Differentiating genome wide expression profile between Prakriti groups

J Transl Med. 2008 Sep 9;6:48. doi: 10.1186/1479-5876-6-48.


Differentiating biochemical and hematological profile between and Prakriti groups.

J Transl Med. 2008 Sep 9;6:48. doi: 10.1186/1479-5876-6-48.


This exploratory study suggests discrete causal pathways for RA etiology in prakriti based subgroups, thereby, validating concepts of prakriti and personalized medicine in Ayurveda.


Traditional Medicine meets Modern Pharmacogenomics

Evid Based Complement Alternat Med. 2011;2011:249528. doi: 10.1093/ecam/nep206. Epub 2011 Jun 8.


Systems biology, a new science of the 21st century, becomes practically available and resembles TCM in many aspects such as study method and designâ&#x20AC;Ś

Zhang et al. Complementary Therapies in Medicine Volume 20, Issue 1 , Pages 93-99, February 2012


ZHENG-Omics Application in ZHENG Classification and Treatment: Chinese Personalized Medicine.

Evid Based Complement Alternat Med. 2013;2013:235969. doi: 10.1155/2013/235969. Epub 2013 Apr 3.


The Correlation between High-Sensitivity C-Reactive Protein, Matrix Metallopeptidase 9, and Traditional Chinese Medicine Syndrome in Patients with Hypertension.

Evid Based Complement Alternat Med. 2013;2013:780937. doi: 10.1155/2013/780937. Epub 2013 Mar 28.


Phlegm-dampness constitution: genomics, susceptibility, adjustment and treatment with traditional Chinese medicine.

Genomics studies found four upregulated genes: COPS8, GNPDA1, CD52 and ARPC3; and six downregulated genes: GSPT2, CACNB2, FLJ20584, UXS1, IL21R and TNPO in the phlegm-dampness constitution. Am J Chin Med. 2013;41(2):253-62. doi: 10.1142/S0192415X13500183.


Sci Rep. 2013;3:1543. doi: 10.1038/srep01543. Imbalanced network biomarkers for traditional Chinese medicine Syndrome in gastritis patients. Li R, Ma T, Gu J, Liang X, Li S.


Understanding molecular mechanisms of traditional Chinese medicine for the treatment of influenza viruses infection by computational approaches. Our results show that TCM compounds can inhibit influenza viral proteins in a multi-target/multi-component manner, revealing the versatility of TCM for treating different influenza virus subtypes, including the recently emerged H7N9.

Mol Biosyst. 2013 Aug 28. [Epub ahead of print]


Merging the medical paradigms Evid Based Complement Alternat Med. 2013; 2013: 731969.


Embedded in all of these systems is lifestyle medicine.


Lifestyle-Induced Chronic Disease Obesity Metabolic Syndrome

Diabetes

Chronic Obstructive Pulmonary Disease

Stroke

Heart Disease

LifestyleInduced Chronic Diseases

Some Cancers

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


Personalized Medicine vs. Personalized Lifestyle Medicine Whatâ&#x20AC;&#x2122;s the difference?


What is “Personalized Lifestyle Medicine”? “Personalized lifestyle medicine is a newly developed term that refers to an approach to medicine in which an individual’s health metrics from point-of-care diagnostics are used to develop lifestyle medicine-oriented therapeutic strategies for improving individual health outcomes in managing chronic disease.”

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.

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SYMPTOMS & DIAGNOSIS

The Trajectory of Disease and Role for Personalized Lifestyle Medicine • • • • • • •

Preclinical Syndromes Low or High Normal Blood Values Low or High Penetrance of Genetic Variants Epigenetic Modifications

INTERVENTION

Pre-Pathological Changes

Disease Diagnosis Abnormal Blood Values Well-defined Symptoms

• •

Diagnosis

Disease Progression Symptom Worsening

Progression

Aggressive Pharmacological Intervention

PERSONALIZED LIFESTYLE MEDICINE Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


What is Personalized Lifestyle Medicine? DIET

ACTIVITY - Nutrition Science – Exercise Physiology – Neuronal Plasticity – Allostatic Load and Resilience Behavioral Genomic Modification Profiling –Testing Psychosocial – SNPs Science and Laboratory – Behavior Epigenetic – Toxic Exposures Programming - Exposome – Systems Functional Biomarkers – Biology – Cellular Biology Clinical Symptoms

Telem etrics Pointof-

- Biochemical Networks – PERSONALIZED Pathophysiology – Molecular Modeling - LIFESTYLE MEDICINE

STRESS

ENVIRONMENT


Differentiation Among Medical Systems

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.

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The Conflict Between Complex Systems and Reductionism â&#x20AC;Śdoes the treatment that addresses a specific disease-related component harm the individual as a whole? Does PLM help you the practitioner to see the patient as a whole?

H. Heng. The Conflict Between Complex Systems and Reductionism. JAMA October 2008; 300:13 (1580-1581)


Patient characteristics to consider in establishing a PLM therapeutic protocol • Age • Lifecycle • Gender • Past medical hx • Family hx • Ethnic background & ancestry • Lifestyle habits • Nutritional status

• Medication use • Dietary supplement use • Physical location & travel frequency • Home and environment • Genetics and mutations • SNPs • Epigenetic patterns

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


Clinical Conditions for PLM • Salt restriction for subtype of hypertension • Dietary cholesterol restriction for subtype of hypercholesterolemia • Dietary saturated fatty acid intake for apoE4 • Gluten restriction for grain intolerance • Fructose restriction for fructose intolerance • Lactose restriction for lactose intolerance • Fava bean restriction for favism • Carbohydrate restriction for glycogen storage disease • Folate supplementation of MTHFR polymorphisms • Lutein supplementation for risk to macular degeneration • Vitamin A supplementation for poor converters of beta-carotene • Vitamin D supplementation for poor 25-hydroxylators • Sulfate supplementation for poor sulfators • CoQ10 supplementation for statin induced myopathy


Clinical Conditions for PLM • Dietary biogenic amine restriction for poor metabolizers (phenylethylamine) • Increased long chain omega 3 fatty acids for poor delta 3 dehydrogenase and elongase activities • Carnitine supplementation for poor acyl-carnitine biosynthesis • Biotin supplementation for specific bone and heart related functions • Glycine supplementation for reduced detoxification capability • Arginine supplementation for reduced eNOS activity • N-acetylcysteine supplementation for poor glutathione biosynthesis • Branched chain amino acid supplementation for individuals with sarcopenia • Magnesium supplementation for antihypertensive meds • Iron restriction for hemochromatosis • Iron supplementation for iron “wasters” • Selenium supplementation for reduced GSH peroxidase activities • DHEA for steroidogenesis deficiencies • Graded aerobic exercise for those with exercise intolerance • Ketogenic diets for epilepsy


The Role of SNPs in PLM • 30,000 genes in human chromosomes • 50% of genome – repetitive sequence • 1.42 M SNPs throughout the sequence • About 1 SNP for every 1000 genes • Influence drug response • Form the basis of PM/PLM Ayu. 2011 Apr;32(2):141-6. doi: 10.4103/0974-8520.92539. Prakriti-based medicine: A step towards personalized medicine. Chatterjee B, Pancholi J.


Nutrition & Dietary Supplements


General Health Recommendations USDA and US Department of Health and Human Services lifestyle recommendations: (1) Prevent overweight and obesity (2) Control calorie intake to manage body weight (3) Increase physical activity and reduce time spent in sedentary behaviors

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


General Health Recommendations (1) Reduce daily sodium intake to less than 2300 mg; further reduce intake to 1500 mg for those 51 yrs+ (2) Consume less than 10% of calories from saturated fat, replace with mono- and poly-unsaturated fat (3) Consume less than 300 mg of dietary cholesterol (4) Keep trans fat as low as possible (5) Reduce intake of calories from solid fats and added sugars (6) Limit consumption of foods that contain refined grains (7) Consume alcohol in moderation â&#x20AC;&#x201C; one drink daily for women; two for men. Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


General Health Recommendations Foods to include: • Increase vegetable and fruit intake • Variety of vegetables • Consume at least half of all grains as whole grains • Increase intake of low-fat dairy • Choose a variety of protein foods • Increase the amount and variety of seafood consumed • Replace protein foods higher in solid fats with those that are lower in solid fats; use oils to replace solid fats. • Choose foods that provide more potassium, fiber, calcium, and vitamin D (includes vegetables, fruits, whole grains, and milk products) Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


AHA for CVD Risk Reduction • Balance calorie intake and physical activity to maintain healthy body weight. • Consume vegetables and fruits • Choose whole-grain, high-fiber foods. • Consume fish, especially oily fish, at least twice per week. • Limit sat fat to 7en%, trans fat to 1en%, cholesterol to 300 mg per day • Minimize intake of foods with added sugars. • Use little or no salt • If you drink alcohol, do so in moderation. Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


American Cancer Society • Maintain normal weight • Be physically active – at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity each week, or an equivalent combination throughout the week • Limit sedentary behavior • Consume a healthy diet, emphasis on plant foods • Limit consumption of processed and red meat • Eat at least 2.5 cups of vegetables and fruits each day. • Choose whole grains instead of refined grain products. • Limit alcohol to no more than 1 drink per day for women or 2 per day for men. Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


American Diabetes Association • Maintain healthy body weight through a lowcarbohydrate or low-fat calorie –restricted diet (effective in short term up to one year) • Physical activity and behavior modification are important for weight loss. • Weight loss medications may be considered in the treatment of overweight and obese individuals with type 2 diabetes and can help achieve a 5-10% weight loss when combined with lifestyle modification. • Bariatric surgery for some individuals. Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


Preventing diabetes (primary prevention) • Among individuals at high risk for developing type 2 diabetes, structured programs that emphasize lifestyle changes that include moderate weight loss (7% body weight) and regular physical activity (150 min/week), with dietary strategies including reduced calories and reduced intake of dietary fat, can reduce the risk for developing diabetes and are therefore recommended. • Individuals at high risk for type 2 diabetes should be encouraged to achieve the USDA recommendation for dietary fiber (14 g fiber/1,000 kcal) and foods containing whole grains (one-half of grain intake). • There is not sufficient, consistent information to conclude that low–glycemic load diets reduce the risk for diabetes. Nevertheless, low–glycemic index foods that are rich in fiber and other important nutrients are to be encouraged. • Observational studies report that moderate alcohol intake may reduce the risk for diabetes, but the data do not support recommending alcohol consumption to individuals at risk of diabetes. • No nutrition recommendation can be made for preventing type 1 diabetes. • Although there are insufficient data at present to warrant any specific recommendations for prevention of type 2 diabetes in youth, it is reasonable to apply approaches demonstrated to be effective in adults, as long as nutritional needs for normal growth and development are maintained.

Personalized lifestyle medicine: relevance for nutrition and lifestyle recommendations. Minich DM, Bland JS. ScientificWorldJournal. 2013 Jun 26;2013:129841. doi: 10.1155/2013/129841. Print 2013.


Role of metabonomics in personalized nutrition Metabonomics, or assessment of metabolic responses based on nutrient sufficiency or deficiency, is a way to characterize the metabolic phenotype of individual and predict their corresponding interactions with gut microbiota, environment, and behavior.

J Proteome Res. 2013 Mar 4. [Epub ahead of print] Toward Personalized Nutrition: Comprehensive Phytoprofiling and Metabotyping. Xie G, Li X, Li H, Jia W.


Phytoprofiling The role of phytochemical modulation of cellular physiology and propose phytochemical profiling, or phytoprofiling, to assist in the facilitation of determining phytonutrient requirements with more effective interventions with plant-derived compounds.

J Proteome Res. 2013 Mar 4. [Epub ahead of print] Toward Personalized Nutrition: Comprehensive Phytoprofiling and Metabotyping. Xie G, Li X, Li H, Jia W.


Food synergy Reducing dietary recommendations to individual nutrients without considering the whole food and its multitude of constituents, including phytonutrients, may not be accounting for â&#x20AC;&#x153;food synergyâ&#x20AC;?.


Personalized nutrition approaches • Iron need and iron transport polymorphisms • Zinc need and polymorphisms • Vitamin D requirement for diabetics with polymorphisms in the vitamin D receptor • The influence of polymorphisms on coenzyme Q10 (CoQ10) need for energy production and its role in cerebellar ataxia: • Folate, MTHFR polymorphisms and depression • B vitamin gene variants and risk to smoking induced lung cancer • Antioxidants and polymorphisms in glutathione S-transferases (GST) • Bitter tasting and body composition differences

J Proteome Res. 2013 Mar 4. [Epub ahead of print] Toward Personalized Nutrition: Comprehensive Phytoprofiling and Metabotyping. Xie G, Li X, Li H, Jia W.


Example 1: MTHFR Polymorphisms


One-carbon metabolism


Homocysteine • Injures endothelial cells • Causes oxidation of protein membranes and proliferation of smooth muscle cells • Depletes nitric oxide and interferes with methylation • Inhibits thrombomodulin expression, thereby promoting coagulation

Postgrad. Med. J. 1996; 72: 513-518; J Nutr 1994;124:1927-33; J Am Board Fam Pract 1998;11(5):391-8


Risk Factors for High Homocysteine

• Inadequate dietary folate, B12, B6, choline, betaine • low fruit/vegetable intake, high processed food intake

• • • •

High protein intake - methionine loading High psychosocial stress Smoking Defect or insufficiency of enzymes that metabolize homocysteine • Gastrointestinal disorders that reduce B12 uptake • Hypochlorhydria • Use of gastric acid inhibitors (Tagamet, etc.) that reduce availability of intrinsic factor


Risk Factors for High Homocysteine (continued) • Family history of: • Atherosclerosis • Peripheral artery disease • Cerebral vascular disease • High homocysteine • Alzheimer’s disease • Kidney disease/renal failure • Elderly and institutionalized • Hypothyroid, postmenopausal, diabetic


“A large body of data indicates that individuals with the T/T C677T MTHFR genotype are prone to mildly elevated plasma total homocysteine levels . . .” –

Bailey LB, Gregory JF. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 1999;129:919-22


Homocysteine metabolism is highly dependent on vitamin-derived cofactors.

The Internet Journal of Anesthesiologyâ&#x201E;˘


Oxidative stress and platelet activation in subjects with moderate hyperhomocysteinaemia due to MTHFR 677 C→T polymorphism.

• In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. • An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation. Thromb Haemost. 2012 Sep;108(3):533-42. doi: 10.1160/TH11-12-0899. Epub 2012 Jul 10.


The Physiology of Bitter Taste Humans are capable of sensing five basic tastes: sweet, sour, salt, umami and bitter. Bitter taste is sensed by bitter taste receptors (T2Rs) that belong to the G-protein coupled receptors (GPCRs) superfamily. Humans have T2Rs that are expressed in the oral cavity, gastrointestinal (GI) neuroendocrine cells and airway cells.

Singh N. et al. Biochem Biophys Res Commun. 2011 Mar 4;406(1):146-51. Epub 2011 Feb 12.


TASTE RECEPTORS

J Cell Biol. 2010 August 9; 190(3): 285–296.


T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. â&#x20AC;Ścommon polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria.

J Clin Invest. 2012 Nov 1;122(11):4145-59. doi: 10.1172/JCI64240. Epub 2012 Oct 8.


BITTER TASTE RECEPTOR POLYMORPHISMS AND HUMAN AGING

PLoS One. 2012;7(11):e45232. doi: 10.1371/journal.pone.0045232. Epub 2012 Nov 2.


Gut effects of bitter tastants

Current Opinion in Pharmacology 2007, 7:557â&#x20AC;&#x201C;562


Bitter tasters have lower BMI

GOLDSTEIN, GRETCHEN L., HENRYK DAUN, AND BEVERLY J. TEPPER. Adiposity in middle-aged women is associated with genetic taste blindness to 6-npropylthiouracil. Obes Res. 2005;13:1017â&#x20AC;&#x201C;1023.


Do polymorphisms in chemosensory genes matter for human ingestive behavior?

TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Food Qual Prefer. 2013 Dec;30(2):202-216.


Do polymorphisms in chemosensory genes matter for human ingestive behavior?

Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior.

Food Qual Prefer. 2013 Dec;30(2):202-216.


Dietary Soy and Cancer • Population differences • Type of soy • Type of tumor • Polymorphisms • Epigenetic mechanisms of isoflavones • Gut microflora conversion to metabolites


Food Intolerances • Involvement of immune system • Possible enzyme deficiency or inadequacy • Detoxification of colonic bacteria-generated metabolites • Individual food substances and food classes – histamines, sulfites, nightshades, gluten, phenylethylamine (PEA) in chocolate, casein, lactose, oxalates


Omega-3 Fatty Acids and APOE • APOE genotype response to EPA and DHA • APOE4 carriers may experience an increase in total cholesterol and LDL-C with DHA supplementation “High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers, which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup.” Atherosclerosis. 2010 Mar;209(1):104-10. doi: 10.1016/j.atherosclerosis.2009.08.024. Epub 2009 Aug 21.


HS-Omega-3 Index A measure of the amount of EPA+DHA in red blood cell membranes expressed as the percent of total fatty acids.

There are 64 fatty acids in this model membrane, 3 of which are EPA or DHA

OmegaQuant速 Harris WS et al. Prev Med 2004;39:212-220.

3/64 = 4.6% HS-Omega-3 Index = 4.6%


Sodium Restriction & HTN • Varying degrees of salt sensitivity exist • Is it universally beneficial? • Lack of assessments and genotypic analyses • Specific gene variants identified, clinical application lacking • Could be influenced by environmental factors such as degree of physical activity


Dietary Cholesterol and Hypercholesterolemia • Dietary limitation of 300 mg cholesterol daily for Americans • Current epidemiological evidence does not support the correlation between dietary cholesterol and increased CHD risk • About ¼ of population is sensitive to dietary cholesterol and responds with increased plasma LDL, but with a compensatory rise in HDL • Dietary cholesterol may help to reduce small dense LDL particles • Egg consumption variability between diabetics and non-diabetics


Tailoring foods and supplements to kinase pathways


Physical Activity


General Health Recommendations A minimum of 150 minutes of moderate activity per week


Exercise as Personalized (a) Are all forms of activity equal for every person? (b) Could maximum benefit be achieved through moderate versus high-level exertion? (c) Are there differences between individual and group responses to activity? (d) What is the optimal duration and intensity for various genotypes and phenotypes? (e) Should there be multimodal interventions or the implementation of a single activity only?

Sports Med. 2013 Mar;43(3):157-65. doi: 10.1007/s40279-013-0018-0. Toward exercise as personalized medicine. Buford TW, Roberts MD, Church TS.


Exercise personalization and HTN • …the American College of Sports Medicine recommends the exercise prescription (ExRx) of 30 min or more of moderate intensity, aerobic activity on most days of the week to lower BP. • Yet, there is considerable individual variability in the BP response to exercise due to genetic and environmental factors that are poorly understood. • We and others have shown there is a genetic component to the BP response to exercise accounting for a significant proportion of this variability.

Curr Hypertens Rev. 2013 May;9(2):130-47.


Genetic Modifiers of Cardiorespiratory Fitness Response to Lifestyle Intervention.

This is the first study to identify genetic variants associated with fitness responses to a randomized lifestyle intervention in overweight/obese diabetic individuals. f RUNX1 and FKBP7, involved in erythropoesis and muscle protein synthesis, respectively, are related to change in cardiorespiratory fitness in response to exercise. Med Sci Sports Exerc. 2013 Jul 29. [Epub ahead of print]


A role for personalization in physical activity • Moderate walking and vigorous running led to similar risk reductions for major chronic diseases in certain populations • Exercise genomics - Nine specific SNPs largely accounted for the heritability of submaximal heart rate training response. • Ahmetov et al. have suggested that the endurance athlete may exhibit a cluster of genetic factors within metabolic pathways related to proportion of slow-twitch muscle fibers and maximal oxygen consumption that may translate into an “elite phenotype”.


Stress Modulation


General Health Recommendations â&#x20AC;˘ Are there any? â&#x20AC;˘ Less emphasis on stress modulation within public health recommendations compared with those of diet and exercise. â&#x20AC;˘ Conceivably difficult to successfully implement lifestyle changes in diet or activity unless there is an underlying adjustment in behavior and locus of control as it relates to stressors.


Exposures to chronic stress are considered the most toxic because they are most likely to result in long-term or permanent changes in the emotional, physiological, and behavioral responses that influence susceptibility to and course of disease. Cohen et al. JAMA, October 10, 2007â&#x20AC;&#x201D;Vol 298, No. 14


Relationship Between Inflammatory SNPs and Emotions • Bereaved participants had higher circulating levels of IL-1RA and IL-6. • This increase could not be explained by proinflammatory genotype frequency differences, or Complicated Grief diagnosis. • However, a GxE effect with the IL-6 -174 SNP moderated individual vulnerability to higher circulating levels of inflammation resulting from bereavement exposure. Brain Behav Immun. 2012 Oct;26(7):1066-71. doi: 10.1016/j.bbi.2012.06.009. Epub 2012 Jun 23. Brain Behav Immun.2012 Oct;26(7):1066-71. doi: 10.1016/j.bbi.2012.06.009. Epub 2012 Jun 23.


Role for personalization in one’s approach to stress • Mind-body medicine practices • Relaxation Response developed by Herbert Benson • Mindfulness-Based Stress Reduction (MBSR) from Jon Kabat-Zinn

• Meditation • Yoga • Diaphragmatic breathing


The relaxation response is powerful in its ability to regulate multiple body systems "Relaxation response (RR) practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways." PLoS One. 2013 May 1;8(5):e62817. doi: 10.1371/journal.pone.0062817. Print 2013.


Tactile Stimulation and Methylation of the Glucocorticoid Receptor Promoter

Tactile stimulation derived from pup LG increases 5-HT activity at the level of the hippocampus, thus increasing NGFI-A expression and its association with the exon 17 promoter, which then initiates an alteration of the methylation state of the exon 17 glucocorticoid receptor promoter. Barry Lester et al. Behavioral epigenetics. Ann. N.Y. Acad. Sci. 1226 (2011) 14â&#x20AC;&#x201C;33


Examples of personalization and stress modulation • Salivary cortisol levels • Stress genotypes • Stress/brain atrophy and interaction with exercise • Allostatic load/resilience


Adrenal Fatigue


Adrenal Fatigue www.genovadiagnostics.com


Environmental Exposures


Metabolic Detoxification and Drug Metabolism: Where PLM Meet


Liver Detoxification Pathways Liska DJ. Altern Med Rev 1998;3(3):187-198


Drug Metabolism and SNPs Liska DJ. Altern Med Rev 1998;3(3):187-198


Included with permission of Dr. Jeanne


Medical Food Program for Chronic Fatigue Alternative Therapies in Health and Medicine. 1995;1(5):62-71

â&#x20AC;&#x153;The results of this study confirm our hypothesis that patients who present with symptoms of chronic fatigue and who are given the specific medical food supplement described would have had a significant improvement in their clinical outcome compared with that of the control patients, who received only the calorie-restricted oligoantigenic diet.â&#x20AC;?


Personalized estrogen metabolism


The Need for Methylating Factors in Estrogen Metabolism


COMT

MTHFR


Toxicity


Individualized Toxin Exposure • Air • Food • Water • Drugs • Radiation • Internally-generated metabolites • Inflammation, lipid peroxidation, oxidative stress, disease states, infections, and microflora


The New Paradigm of the T2DM Epidemic

EpigeneticsToxicity Interface

Lee DH, Steffes MW, Jacobs DR Jr. Diabetologia. 2008 Mar;51(3):402-7. Epub 2007 Dec 11.


GGT and POPs


â&#x20AC;&#x153;BMI was not associated with prevalent type 2 diabetes when GGTP was low normal, suggesting that obesity itself is not a sufficient risk factor for type 2 diabetes.â&#x20AC;? Clin Chemistry 2007; 53: 1092-98.


Pollutants and mitochondrial dysfunction • Metabolic syndrome and obesity suggested to be a result of “toxic” inhibition by POP’s of mitochondrial bioenergetics • Lim, Cho and Lee, Ann NY Acad Sci 2010;1201:166-76. • Lee, Cho Lim and Shim, Biochem Biophys Acta 2010; 1800: 282-9.

• Patients chronically exposed to pesticides have elevated GGT and oxidative stress • Gas station workers exposed to lead have elevated GGT • Cabaravdic and Kusturica, Med Arh 2010; 64: 107-9.

• GGT is seen as a surrogate biomarker for oxidative stress • Lee, Bloomhoff and Jacobs, Free Radical Res 2004; 38: 535-9


â&#x20AC;&#x153;The well characterized GGT 1 is an extracellular enzyme that is anchored to the plasma membrane of cells. Thus it hydrolyses and transfers gamma-glutamyl moieties from glutathione to other acceptors. As such it is critical for the function and metabolism and recycling of glutathione.â&#x20AC;? Human Genetics 2008; 123: 321-32.


Serum GGT as a marker for exposure to xenobiotics Lee DH, Steffes MW, Jacobs DR Jr. Diabetologia. 2008 Mar;51(3):402-7. Epub 2007 Dec 11.


“…serum GGT activity may reflect amounts of glutathione conjugates formed during the metabolism of xenobiotics.” “Some POPs are conjugated to GSH for their metabolism, and exposure to high amounts of certain POPs in occupational or accidental settings increase serum GGT activity.”

Lee DH, Steffes MW, Jacobs DR Jr. Diabetologia. 2008 Mar;51(3):402-7. Epub 2007 Dec 11.


And even metabolic syndromeâ&#x20AC;Ś


And Alzheimer’s disease…

“Serum GGT levels were increased significantly in Alzheimer Disease patients. To evaluate the role of GGT as a marker of oxidative stress in AD further studies are needed.”


New Research on POPs and Weight Loss

“Serum concentrations of most POPs were higher in those with long-term weight loss…”


A Systems Biology Perspective on the Effects of Pollution Notably, PM is known to alter epigenetic markers (e.g., DNA methylation and histone modifications), which may contribute to air pollution-mediated health consequences including the risk for cardiovascular diseases.

Curr Pharmacogenomics Person Med. 2012 Dec;10(4):314-321.


Putting together a patient PLM protocol


We are intertwining networks. “…humans are simultaneously biological and cultural beings, which means that physical and ideational networks are enfolded in and unfold from one another.” Sumara DJ, Davis BA. Correspondence, coherence, complexity. English Teach Pract Critque. 2006;5:34-55.


Team of practitioners


The power of biomarkers

• Laboratory tests • Functional tests • Point-of-care diagnostics


Tracking devices


The IFM Lifestyle Journal


Sample Lifestyle Journal


The Interpretation & Translation • Genetic tests • Laboratory biomarkers • Functional tests • Physical diagnosis • Patient education (PLMI)


A typical patient’s experience with PLM INITIAL • Genetic tests run by major labs • SNP evaluation • Laboratory biomarkers • Evaluation of physical symptomatology • Assessment of lifestyle factors ONGOING • Tracking using applications • Virtual coaches


My own experience with PLM


Grandma and me


Increased risk for breast cancer


COMT

MTHFR


Case Study Utilizing PLM Scott Rigden, MD


Case Study â&#x20AC;˘ 67 year old female who presented with a longstanding, severe obesity problem. â&#x20AC;˘ She had severe osteoarthritis and degenerative damage in both knees, causing severe pain and marked restriction of activities. â&#x20AC;˘ On her initial appointment, she could barely walk into the office from the handicapped parking spot. However, at this time, surgery could not be done because of her excessive weight, making successful surgery very unlikely.


Case Study • Her orthopedist insisted that she reduce from her present weight of 258 pounds to less than 200 pounds before he would even begin to initiate any procedures. • Also, M was having a number of other medical problems related to her obesity including poor sleep, averaging only two to four hours a night, varicose veins, hypertension, depression, low energy and GERD. • She also had hypothyroidism, depression, and fatigue.


Case Study • To cope with chronic heartburn, M. had to take at least eight Tums daily; in addition, she had tried numerous other acidblocking medications to no avail. Other medications included Lexapro 5-10 mg daily, Levoxyl 25 mcg daily, Lisinopril 40 mg daily, Triamterene-HCTZ 37.5/25 mg daily, Tylenol arthritis formula 2 daily, and Motrin as needed (often 4-6 daily). • She had a cholecystectomy in the 1980's. • M's family history was positive for Diabetes Mellitus and she had great concern she also would develop this problem.


Case Study Measurements and Labs:

MTHFR SNPs? APOE3/4?

• Height: 64 inches • Weight: 258 pounds • Blood Pressure: 140/72 • % Body Fat: 40.6 • Waist Circumference: 51 inches • Electrocardiogram (EKG): Abnormal, Atrial Fibrillation • TSH: 2.43 (normal) • Fasting Glucose: 82 (normal) • Total Cholesterol 224: goal under 200 • Triglycerides 120: normal • HDL Cholesterol 61: normal • LDL 143: goal under 130


Case Study Assessment: (1) Obesity, markedly impairing the patient's lifestyle (2) Osteoarthritis of the knees, severe (3) Hyperlipidemia, (elevated cholesterol and LDL cholesterol) (4) Varicose Veins (5) Hypothyroid (6) Hypertension (7) Depression (8) Fatigue (9) GERD, causing chronic heartburn with acid reflux, aggravated by obesity (10) Sleep Disorder, previously diagnosed by a specialist to have Obstructive Sleep Apnea secondary to the patient's weight.


Case Study Treatment Plan • Modified Mediterranean Food Plan and started her on Medical Food for Cardiometabolic Syndrome, 2 scoops twice daily. Blood sugar support tablets, one twice daily. • For exercise, it was suggested that she start a "4 minute miniwalk program," in which she was advised to walk slowly around her house for 4 minutes and then rest. • Hopefully, she could work up to five such efforts daily for a total of 20 minutes of controlled walking. • The hope was that as she lost weight and felt better, we could gradually increase her walking.


Case Study ONE MONTH LATER â&#x20AC;˘ She weighed 244.2 pounds and felt much better. Her blood pressure was 118/76 and she was walking five to ten minutes at a time on her treadmill. TWO MONTHS LATER â&#x20AC;˘ M continued to feel better and her blood pressure continued to improve. She cut her blood pressure medication down and noted her heartburn was improving. Her weight was 234.6 pounds, blood pressure 108/62, and her lab showed a remarkable improvement in cholesterol, dropping to 152, and LDL cholesterol, now at 89.


Case Study SIX MONTHS LATER â&#x20AC;˘ Our patient is positive and happier with her life. She is decreasing all of her medications and walking 30 minutes daily on her treadmill! Her weight is 194.8 pounds and blood pressure 122/68. SEVEN MONTHS LATER â&#x20AC;˘ M is now wearing a pedometer. She is thrilled to share that she felt well enough to go on a family vacation to Disneyland with six grandchildren. This would have been impossible seven months ago. M averaged walking 7000-10000 steps daily for nine days in a row at Disneyland! Her heart is no longer in atrial fibrillation; it now is in regular sinus rhythm. Her weight is 188.8 pounds and blood pressure 108/68.


Case Study ONE YEAR LATER M continues to follow her diet and now takes medical food two scoops daily. Her EKG is completely normal. She has excellent energy, is walking 4-5 miles daily, and is off all of her medications except for her thyroid and an occasional Ibuprofen or Acetaminophen. M weighs 164 pounds with a 38 inch waist and body fat of 25.9 %. TWENTY-ONE MONTHS LATER M weighs 142 pounds, follows the food plan and lifestyle protocol and continues to take her Medical Food, two scoops daily. She is walking several miles daily with little discomfort. She has not gone back to her orthopedist and has no plans at this time for any surgery.

M said she has not felt this vigorous and healthy since she was a teenager!!


Our Mission: Transforming health care through personalized lifestyle medicine Our Vision: To be the global leaders in the promotion of personalized lifestyle medicine Our Website: www.plminstitute.org


The Interrelationship of Medical Systems PREVENTION

TREATMENT Lifestyle Healthcare

Public Health Recommendations

P4 Medicine Personalized, Preventative, Predictive, Participatory

Personalized Medicine

Lifestyle Medicine Personalized Lifestyle Healthcare Individualized Therapies

Functional Medicine Operational System


Conclusions • Personalized medicine has its roots in ancient medical systems. • The sequencing of the genome together with cutting-edge technology advances has resulted in the application of personalized medicine in the area of drug metabolism. • Personalized lifestyle medicine incorporates an individualized approach to food, supplements, activity, environment, and stress modulation. • Tailoring therapies to a patient should result in the best outcome for the patient.


Appendix


Case Study - Eczema • “John,” presented initially as a 54 year old professional engineer with chronic severe eczema as well as multiple medical problems including obesity, diabetes mellitus Type 2, hyperlipidemia, osteoporosis, S/P PTH disease and surgery, hypertension, obstructive sleep apnea with C-PAP, kidney stones, osteoarthritis, history of multiple allergies as a youth, GERD, multiple medications, low energy, elevated life stress, and diverticulitis/diverticulosis. His family history was positive for lung disease. Past medical history included parathyroid surgery in 2008, pulmonary embolism in 2003, and a tonsillectomy as a youth. His medications included Prilosec (omeperazole), Acetaminophen, Ibuprofen, Excedrin, Lotensin 20-25mg one daily, Norvasc 5 mg daily, and Fosamax (previously had been on Boniva). His physical examination was remarkable for obesity and extensive, severe atopic dermatitis/eczema on his extremities, trunk, scalp and hairline.


Case Study - Eczema • Case Study #7095, “John,” presented initially as a 54 year old professional engineer with chronic severe eczema as well as multiple medical problems including obesity, diabetes mellitus Type 2, hyperlipidemia, osteoporosis, S/P PTH disease and surgery, hypertension, obstructive sleep apnea with C-PAP, kidney stones, osteoarthritis, history of multiple allergies as a youth, GERD, multiple medications, low energy, elevated life stress, and diverticulitis/diverticulosis. His family history was positive for lung disease. Past medical history included parathyroid surgery in 2008, pulmonary embolism in 2003, and a tonsillectomy as a youth. His medications included Prilosec (omeperazole), Acetaminophen, Ibuprofen, Excedrin, Lotensin 20-25mg one daily, Norvasc 5 mg daily, and Fosamax (previously had been on Boniva). His physical examination was remarkable for obesity and extensive, severe atopic dermatitis/eczema on his extremities, trunk, scalp and hairline.


â&#x20AC;˘ Weight: 307.4 pounds Ht.: 66 inches BP 142/92. RAST IgG4 tests â&#x20AC;˘ showed severe 5+ reactions to casein, milk, egg whites, and egg yolks with a 3+ reaction to navy beans; 25-OH-D level 41: TSH: 2.50, Free T3 2.9, Free T4 1.1; Plasma zinc: 91; ANA negative; Cocci screen negative; anti-streptolysin antibodies negative; random glucose 179; cholesterol 231; triglycerides 303; fasting insulin 32; Apolipoprotein A1 and B negative; CRPhs 10; celiac screen negative; CBC, Vit. B12 and Folate levels normal; fasting glucose, 148; ALT 86; A1C 7.4; stool cultures show 0 growth of lactobacillus and 4+ vigorous growth of multiple pathogenic bacteria, including 2 species of Citrobacter, Hafnia pseudomonas and klebsiella.; Candida 1+, no parasites; all bacteria sensitive to Cipro


• INITIAL ASSESSMENT • 1.

Type 2 Diabetes Mellitus with hyperinsulinemia and insulin resistance

• 2.

Elevated CRPhs, confirming high levels of inflammation

• 3.

Hyperlipidemia

• 4. Food hypersensitivities with a history of chronic allergic issues for his entire life with a chronic case of refractory, severe eczema • 5.

Intestinal dysbiosis with no lactobacillus growth, several bacterial pathogens and candida overgrowth

• 6.

Elevated ALT with probable NASH

• 7. Chronic GI problems with GERD and diverticulisits/diverticulosis,; also on Prilosec for years, which may be contributing to a chronic malabsorption issue • 8.

Hypertension

• 9.

Osteoporosis with a history of parathyroid disease and surgery

• 10.

Fatigue

• 11.

High stress

• 12.

Obstructive sleep apnea with C-PAP

• 13.

Borderline Vit. D levels.

• 14.

Osteoarthritis (knees and right ankle)

• 15.

History of kidney stones


• TREATMENT PLAN • 1. Start low glycemic load diet, the modified Mediterranean diet, with 5-6 feedings per day including a specially designed medical food with select kinase response modifiers designed to normalize glucose-insulin metabolism, 2-4 scoops daily. • 2. In addition to a low glycemic load diet, eliminate casein, milk, egg whites and yolks, and navy beans from his diet. • 3. After 10 days of Rx Cipro, take saccharomyces boulardii supplementation for 3 weeks followed by a high potency dairy-free probiotic twice daily for an indefinite period of time. • 4. EPA/DHA 2 grams twice daily, modified folic acid 400 mcg twice daily, micronutrient support for glucose/insulin metabolism (contains chromium, lipoic acid, cinnamon compounds, etc.) 1 tab twice daily, 4000 i.u. of Vit. D3 daily • 5.

Start two ten minute walks daily.


• PROGRESS NOTES/FOLLOW-UP VISITS • 2 Months Later • Patient reports improved energy, digestion and elimination, skin and musculoskeletal pain. He is more “clear-headed.” Weight is 301.6 lb., down 9 lb. BP is 122/68 (previously 142/92). • 4 Months Later • Patient reports better energy, GI tract is much better and he has been able to discontinue omeperazole. Skin condition continues to improve. Blood pressure is 118/64 and weight is now 291.8 lb. (down 19 lb.). • 5 Months Later • Patient reports marked improvement in skin, GI tract, and energy. Weight is now 282.2 lb., decreased from 310.2 lb., and BP is 122/78. Labs: (previous in parentheses) CRPhs 5.6 (10.0); A1C 6.9 (7.4); fasting insulin 20 (32); 25-OH-D 53 (41); cholesterol 208 (224); triglycerides 128 (163); LDL 145 (154); fasting glucose 135 (148); ALT 20 (86) We will start tapering Norvasc. • ONE Year Later • Patient is off Norvasc, weight 274.4 lb. (down 36 pounds), BP 120/80. Plan to decrease Lotensin to 10/12.5. • TWO Years Later • Feeling and functioning well. Weight is 255 lb., BP 120/78 • DEXA bone density much improved, showing normal bone density in the lumbar spine, borderline normal levels in hips, with persistent osteopenia in the left forearm.


• 2.5 Years Later • Initial

Present

• • Weight

310.1 lb.

251 lb.

• BP

142/92

• FBS

148

109

32

8

• A1C

7.4

6.3

• Triglyc.

163

99

• HDL

43

66

• CRPhs

10.0

0.9

• Fasting Insulin

122/78

• Skin( 0-10)

10

1,2

• GI Sx’s (0-10)

9-10

1-2

• Energy(0-100)

40-50

80-90

• Mskel pain (0-10)

6-7

0-1


• this gentleman’s chronic severe inflammatory skin condition was a marker for multiple physiological imbalances in the body that were producing inflammation that impacted multiple systems of the body, e.g., cardiovascular, glucose-insulin, musculoskeletal, bone density, GI, etc. By normalizing inflammation originating from adipocytes and the arachidonic cascade with blood sugar-insulin management, removing food triggers and GI sources of chronic inflammation, “John” has re-invented himself. He continues to work on his weight and we are hopeful some day to have a BMI closer to 30. His skin condition, ironically, was the key “clue” to help us understand and develop a successful personalized lifestyle medical program.


â&#x20AC;˘ Initial Presentation â&#x20AC;˘ Mr. Z presented as a 43 year old Pima Native American to our office with a weight of 473 pounds. Other than fatigue, dyspnea with exertion, and mild knee pain, his past medical history and review of systems was relatively unremarkable. Our metabolic work-up discovered a mild hypothyroid condition with a TSH of 6.78, a borderline A1C of 6.2, and elevated fasting insulin of 30. With a diagnosis of Metabolic Syndrome and hypothyroidism we initiated a high protein, low carbohydrate diet and prescription of Levothyroxine. He lost about 50 pounds and had improved lab work, but due to a variety of reasons he was lost to follow-up after one year.


â&#x20AC;˘ Two Years Later â&#x20AC;˘ Mr. Z returned to our office two years later and had maintained his weight of 427 pounds. However, he had not been regularly taking thyroid replacement and now reported two other areas of medical problems: (1) he could not increase muscle mass even with aggressive weight lifting, had developed gynecomastia, and had markedly decreased libido, which taken together suggested hypogonadism; (2) he was snoring severely at night with irregular, sometimes long pauses between breathing and was somnolent during the day. Evaluation at this time revealed TSH of 7.21, fasting insulin of 27, and total testosterone of 107 (normal 325-1000), a free testosterone of 17.2 (normal 35-79). It was interesting to note his fasting glucose was 90, total cholesterol 181, triglycerides 179, HDL 35, and LDL 117. His triglyceride to HDL ratio of 5.2 corroborated persistent insulin resistance. A sleep study confirmed obstructive sleep apnea and CPAP was initiated.


• ASSESSMENT • 1. Ethnicity, “Apple ” fat distribution, elevated insulin levels, borderline A1C, an elevated triglyceride/HDL ratio, all confirming or contributing to Metabolic Syndrome. • 2.

Hypothyroidism-sub-optimally regulated

• 3.

Hypogonadism

• 4.

Obstructive Sleep Apnea requiring CPAP


â&#x20AC;˘ Treatment Plan â&#x20AC;˘ Low Glycemic Load Diet with medical food designed to regulate blood sugar and insulin, workout 60 minutes 34 times week, micronutrient support with chromium, lipoic acid, cinnamon compounds, EPA/DHA one gram twice daily. Take 225 mcg levothyroxine daily, regularly use CPAP, regulate testosterone with an injection of 5 mg every 2-4 weeks.


• FOUR YEARS LATER • Initial

4 Years Later

• Weight

473 lb.

309 lb.

• TSH

6.8

2.59

• FBS

130

86

• A1C

6.2

5.3

• Fasting Insulin

30

8

• Testosterone

107

533

• Cholesterol

181

157

• TG

179

90

• LDL

117

95

• HDL

35

45


The Future of Personalized Lifestyle Medicine