Visit 1: Optimal Weight and Metabolic Health PowerPoint

Transcript

1. The Approach to Optimal Weight and Metabolic Health Eric Hassid, M.D., FMNM, ABAARM Functional Medicine Physician Sutter Institute for Health and Healing Roseville, California
2. Presentation overview • Functional Medicine Principles • Cardiovascular/Cerebrovascular Disease • Weight and Metabolic Health Disruption • Cardiometabolic Risk Matrix • Necessary Steps for Optimal Weight and Metabolic Health • Foundational Elements • What is Hormesis? • Hormetic Activities Relevant to Optimal Weight and Metabolic Health: – Diet and Nutrition – Exercise • Take Away Points • References and Recommended Readings
3. Functional Medicine Principles • Achieving health is the cornerstone of combating and preventing chronic disease • Genetics accounts for 20% of our health destiny while nutrition, lifestyle habits and environment account for 80% • The implementation of healthy nutrition and lifestyle habits can have a substantial positive impact on both disease management as well as disease prevention, in great part by influencing our genetic expression; and this includes optimal weight and metabolic health • Optimizing weight and metabolic health are critical to preventing many chronic diseases such as diabetes, heart attack, stroke and dementia
4. Cardiovascular/Cerebrovascular Disease General Information • Heart attack and stroke represent close to 30% of all global deaths • The classic main lifestyle risk factors for cardiovascular and cerebrovascular disease are tobacco use, unhealthy diet, decreased physical activity, and excessive alcohol use. • Although high blood pressure and high cholesterol (dyslipidemia) do play a significant role in cardiovascular and cerebrovascular disease, when it comes to approaching prevention and management, the story is much more complex…in comes “metabolic health”
5. • About 25-30% of Americans have weight and metabolic health challenges (insulin resistance) • Much of this has developed as a result of poor food choices, environmental toxins, increased sedentary lifestyle, poor sleep, and increased life stressors • As a result of the increased obesity challenge in America, many are attempting to solve the problem with a variety of “diets” • Although well intended, these diets often produce either no significant change in overall lean body weight or they result in temporary weight loss with an eventual end result of the “yo-yo” effect • Although it is true that calories out need to be greater than calories in, there is more to the weight loss story • The reason why many diets do not succeed in the long term is that they fail to address many of the other complex physiological and psychological factors that are taking place Weight and Metabolic Health Disruption General Information
6. Weight and Metabolic Health Disruption The Role of Visceral (Belly) Fat • Excessive visceral (belly) fat: – Visceral fat is a very dynamic organ which, at a certain threshold of size, has the potential to become pathogenic and produce inflammatory and hormonal like chemicals – Excessive belly fat gets to the point where it outstrips its own blood supply causing fat hypoxia (lowered fat circulation and oxygen supply) and cell death which result in • Increased influx of inflammatory white blood cells into the area (M2 macrophages) • Increased visceral fatty acid release into circulation which deposits into other organs like liver (fatty liver) and muscle (fatty muscle) which increase insulin resistance (excessive muscle fat causes mitochondrial dysfunction, increases unmetabolized fatty acids, which impairs insulin-glucose transporter function) • M2 macrophages produce excessive inflammatory chemicals and hormonal-like substances which also increase insulin resistance and all its negative consequences – Body composition analysis via bio-impedance analysis (BIA) is a simple, yet accurate, way of accessing total body, lean body mass and visceral fat, the latter of which correlates with cardiometabolic disease NOTE: Be aware of “skinny fat” which can be determined via BIA testing
7. Weight and Metabolic Health Disruption Visceral Fat Dysfunction
8. • The biomarker representations of the pathogenic visceral fat we just talked about, which relates to insulin resistance, are referred to as the “metabolic syndrome” • Metabolic syndrome criteria are as follows (Harmonized Consensus in 2009): – 3 or more out of 5 following criteria are needed to fulfill this diagnosis: • Increased serum triglyceride levels (>150 mg/dl) • Lower healthy HDL levels (< 40 mg/dl in men, < 50 mg/dl in women) • Higher fasting blood sugar levels (> 100 mg/dl) • High blood pressure (>130/85) • Abdominal obesity (> 35 inches for women, > 40 inches for men) Weight and Metabolic Health Disruption Insulin Resistance and the Metabolic Syndrome
9. Weight and Metabolic Health Disruption How We Get There • The End Result: – Metabolic inflexibility and inefficiency • Poor fatty acid oxidation (cannot burn fat; instead, store fat in muscle and liver) • Poor aerobic glycolysis (cannot burn sugar, aerobically) • Overall lower energy production (up to 30% less ATP production) • How We Got to This End Result, Physiologically: – Poor mitochondrial function/repair/biogenesis leads to poor energy production (ATP) resulting from • Excessive inflammation • Excessive free radical stress and lowered nitric oxide levels (which, in great part, comes from inefficient/damaged mitochondria) • Insulin resistance (chicken or the egg?) which increases inflammation and free radical stress, which leads to mitochondrial dysfunction • High circulating glucose (secondary to insulin resistance/diabetes) binds to fats and proteins and causes them to be damaged and dysfunctional (advanced glycation end products-AGE’s); this leads to advanced aging and chronic disease NOTE: Mitochondrial dysfunction can lead to insulin resistance AND insulin resistance can lead to mitochondrial dysfunction
10. Weight and Metabolic Health Disruption How We Get There (Continued) • Pathological Manifestations of long-standing insulin resistance/hyperinsulinemia (metabolic, inflammatory consequences): – Diabetes – Dyslipidemia – Hypertension – Vascular disease – Heart disease – Stroke – Cancer – Dementia
11. Weight and Metabolic Health Disruption Contributing Factors • Hormonal dysregulation (which can be the cause and be the result of insulin resistance) – High cortisol/norepinephrine/epinephrine/RAAS – Poor insulin signaling – Leptin resistance – Low adiponectin – Low cellular T3 – Low testosterone (excessive aromatase activity in visceral fat converts testosterone to estrogen) – Estrogen dominance/low progesterone (women) – Low DHEA – Low HGH – Low melatonin – Low vitamin D
12. Weight and Metabolic Health Disruption Contributing Factors • Elevated uric acid levels (increases inflammation and oxidative stress at high levels-high fructose in diet elevates uric acid production) • Environmental toxins (smoking, alcohol, heavy metal exposure, and organophosphate pesticides) • Energy excess (food consumption >> energy burning=reductive stress) • High CHO, high saturated fat, high processed food diet (high calorie, low nutrient dense diet) • Low physical activity and exercise • Nutrient deficiencies (carnitine, coenzyme Q10, magnesium, niacin, thiamin, riboflavin, iron, etc.) • Altered microbiome and intestinal permeability • Medications (Depakote, TCA’s, anti-psychotics, etc.) • Excessive emotional stress and/or pain • Poor sleep • Altered circadian biology • Genetics (diabetes predisposition, familial hypercholesterolemia, MTHFR mutation, the latter of which can predispose to excessive clotting and vascular disease from depleted NO and elevated homocysteine) • Inadequate adaptive physiological stress stimuli (hormesis)
13. Cardiometabolic Risk Matrix
14. Necessary Steps for Optimal Weight and Metabolic Health Management • FIRST: Focus on foundational elements • THEN: Enhance cellular adaptability and resilience (hormesis effect)
15. Necessary Steps for Optimal Weight and Metabolic Health Management: Foundation Elements Foundational Elements – Support • Healthy oxygenation • Hydration • Nutrition (mito food plan) • Toxin reduction/elimination (alcohol and smoking) • Elimination • General GI function – Promote rest, relaxation and repair (this is really important!!) through • Stress reduction • Optimal restorative sleep • Support healthy circadian biology • Life balance
16. What is Hormesis? • Hormesis refers to the “existence of biological defense mechanisms that are triggered by stressful but sub-toxic stimuli and culminate in the protection, repair, and enhancement of biological systems at the molecular, cellular, and organismal levels” (1) (1) Rehana et al., Enhancing and Extending Biological Performance and Resilience; An. International Journal, July-September 2018, 1-24
17. What Doesn’t Kill You Makes You Stronger!
19. Hormesis Biological Effects (2) • Mobilization of stem cells • Reduction of inflammation and oxidative/nitrosative stress • Upregulation of endogenous anti-oxidants • Enhancement of autophagy (auto-digestion of old cells and old misfolded proteins) • Enhancement of mitophagy (recycling of mitochondria) • Mitochondrial biogenesis • Activation of uncoupling proteins within ETC of mitochondria (enhances thermogenesis/metabolism and helps to reduce mitochondria generated free radicals) • Increases brown fat (BAT) which improves metabolism • Reduced abnormal cellular growth and proliferation (e.g. reduce cancer potential, autoimmunity) • Increased brain derived neurotrophic factor (BDNF) • Improved autonomic regulation (increased parasympathetic tone) • Enhanced fatty acid oxidation • Improved hormonal regulation and signaling (cortisol, insulin, thyroid, sex hormones, HGH, adiponectin, leptin, etc.) (2) Longo et. Al., Fasting: Molecular Mechanisms and Clinical Applications; Cell Metabolism. February 2014, Volume 4, 181-192
20. Necessary Steps for Optimal Weight and Metabolic Health Management Hormetic Elements • DIET AND NUTRITION – Carbohydrate restriction/mito food plan – Intermittent fasting – Supplementation with natural hormetic-like substances • EXERCISE
21. Diet and Nutrition Carbohydrate Restriction/Mito food plan • This diet restricts carbs to 50-100 grams per day while increasing consumption of healthy fats and oils, moderate amounts of healthy protein to maintain lean body mass, low glycemic vegetables and fruits. The standard keto diet is less discriminate on types of fat consumed; also, less consumption of vegetables and fiber which could pose some long-term risks. The mito food plan keeps starchy vegetables, grains and fruit to a minimum (berries are the fruit of choice, non-starchy vegetables are encouraged), but emphasizes non-starchy vegetables, nuts and seeds, healthy fats and oils, spices, healthy animal and non-animal protein sources; clearly a healthier version of the standard ketogenic diet. Keeping carbs under 50 grams per day may be necessary to achieve a ketogenic effect. • This diet will force the body to oxidize fat and create ketone bodies, specifically, beta- hydroxybutyrate (BHB), acetoacetate and acetone, since sugars are in low supply • Ketone bodies can be utilized by the brain in lieu of glucose as an effective energy source • Research is supporting the notion that ketones like BHB are signaling molecules that ultimately upregulate anti-oxidant defenses and mitochondrial biogenesis (3) (3) Miller et al., Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health. Journal of Nutrition and Metabolism, 2018, 1-27
25. Diet and Nutrition Benefits of Carbohydrate Restriction/Ketogenic Diet • Cardiovascular health • Metabolic syndrome and diabetes • Optimal weight and body composition (loss of fat mass, maintenance of lean body mass) • Migraine headaches • Epilepsy • Neurodegenerative disease • Mood disorders • Chronic pain • Cancer • Wellness and optimal aging
26. Diet and Nutrition Forms of Intermittent Fasting (4) • Intermittent Fasting (Fasting from 16-48 hours) – Time Restricted Feeding (TRF) • Eating all food within a specified time window • 8 hours feeding time, 16 hours fasting time is most commonly recommended • Consider eating from 9 to 5 or 10 to 6 with a goal of 75% of all calories/carbs consumed before 2 PM • Studies show improved weight and blood pressure without change in actual diet quality or calories – Intermittent Fasting (IF) • Consuming no more than 40% of normal calories twice per week (not consecutive) or every other day • May be helpful in weight management • Periodic Fasting (Fasting for over 48 hours) – Fasting Mimicking Diet or FMD • 5 consecutive days of low caloric intake, monthly for 3 months, then quarterly thereafter (Dr. Longo research) • 1100 kcals day 1, 800 kcals day 2, 500 kcals day 3, 800 kcals day 4, 1100 kcals day 5 • Very low carb, high fat, modest protein intake (soups, low glycemic load smoothies, nut bars, olives, etc.) • Studies suggest potential benefit in weight loss, blood pressure, inflammation control and a variety of chronic diseases • Fasting for 72 hours or more may be necessary to affect autophagy and mitophagy; FMD achieves this goal (4) Mattson et. al., Impact of Intermittent Fasting on Health and Disease Processes; Aging Research Reviews. Volume 39, October 2017, 46-58
27. Diet and Nutrition Intermittent Fasting Benefits (4) • Animal Studies – Cardiovascular disease – Optimal weight and body composition – Insulin signaling and prevention of metabolic syndrome/diabetes – Neurodegenerative disease – Cellular resilience and aging • Human Studies (preliminary studies-many more studies needed!) – Cardiovascular disease – Optimal weight and body composition – Insulin signaling and prevention of metabolic syndrome/diabetes – Adjunctive cancer therapy (small trials) – Multiple sclerosis (small trials) (4) Mattson et. al., Impact of Intermittent Fasting on Health and Disease Processes; Aging Research Reviews. Volume 39, October 2017, 46-58
28.  Metabolically Supportive Supplements  Fish oil (EPA predominant form likely better for cardiovascular protection)  Olive oil  Chromium  Inositol  Soluble fiber  Guar gum  Psyllium husk  Cinnamon extract  Coenzyme Q10  Vanadium  Magnesium  Aged garlic extract  Pomegranate NOTE: The above nutrients support healthy insulin signaling, lipid level normalization, vascular health, inflammation reduction, re-dox balance, and/or mitochondrial energy production (each supplement mentioned above will have one or more of the above stated effects) Diet and Nutrition Metabolically Supportive Supplements
29. Diet and Nutrition Natural Hormetic-like Supplements  Nutritional Supplements (5)  Curcumin  Quercetin  Green tea extract  Sulphorophane  Pyrroloquinoline quinone (PQQ)  Resveratrol  Berberine  Bergamot  Pterostilbene  Alpha lipoic acid  Acetylcarnitine  Nicotinamide mononucleotide (NMN)  PBS-125 NOTE: The above nutrients work on a variety of cellular resilience pathways such as AMPK, NRF-2, PGC-1 alpha, and NFKb which collectively lead to increased metabolic efficiency, mitochondrial biogenesis, endogenous anti-oxidant production, and anti-inflammatory pathway activation (5) Lee et al., Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemical: Focus on the Nervous System; Pharmacological Reviews. Volume 66, July 2014, 815-868
30. • Medibolic, 1.5 scoops per day (Thorne) OR Phytomulti, 1 twice per day with food (Metagenics) • Super Omega 3-6-9, 2 per day with food (NOW) • Orthomega Fish oil, 2 per day with food (Orthomolecular Products) • Metabolic Health Formula, 3 twice per day with meals (Compounded Nutrients) Metabolic Health Supplement Suggestions for Your Consideration
31. Exercise • Weight training is necessary to build muscle mass and improve resting metabolic rate which is critical for successful weight and body composition management • High intensity interval training (HIIT) may be more effective at improving body composition than standard longer bouts of aerobic exercise due to the after-burn effect of this type of exercise • Studies suggest that combining weight training with HIIT, as opposed to standard aerobic exercise, does not hinder the desired muscle building effects of concurrent exercise due to competing biochemical effects associated with standard aerobic exercise and resistance training (6) Musci et. al., Exercise-induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension. Sports 2019, Volume 7, 1-18
32. Exercise • Exercising (primarily aerobic type) before breaking the 16 hour fast creates a larger energy deficit which may lead to a greater adaptive physiological (hormetic) effect (the increased AMP/ATP and NAD+/NADH ratios activate energy sensing molecules like AMPK and SIRT-1 which lead to the stimulation of PGC-1 alpha and all the desired adaptive physiological changes like mitochondrial biogenesis, upregulation of anti-oxidants, etc.) (6) • It may be best to avoid supplements right after exercise in order to allow for the exercise induced “free radical generation” effect which leads to the desired physiological adaptation and hormetic effect, specifically, NRF-2 pathway and the genetic upregulation of endogenous anti- oxidant, anti-inflammatory and mitochondrial biogenesis pathways (studies on the free radical scavenger, vitamin C, and exercise, for example, have shown an adaptation blunting effect while reducing delayed onset muscle soreness-so, in effect, it allows you to feel better after exercise, but not prevents you from making much progress!) • Consuming BCAA’s and/or whey protein around or after exercise along with some carbs like berries (berry-whey smoothie) can support recovery and augment the desired muscle anabolic effect resulting from resistance training (6) Musci et. al., Exercise-induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension. Sports 2019, Volume 7, 1-18
33. Take Away Points • Successful weight and metabolic health management requires effort and strategy • Focusing on the foundational elements (nutrition, sleep, emotional health, activity, GI health, environmental toxin reduction/elimination) is a critical first step • The next step is to engage in activities designed to promote adaptive physiological changes (hormetic effect) which is critical to achieving optimal weight and metabolic health management; these stimuli include carbohydrate restriction (mito food plan), intermittent fasting (at least time restricted feeding supporting healthy circadian biology) and challenging exercise with resistance training and high intensity interval training HIIT)
34. Recommended Educational Resources • Wellness Resource Guide, 3rd edition; Eric Hassid, M.D., 2023 (can be purchased at newuhealth.net) • Metabolic Autophagy; Slim Land, 2019 • Cardiometabolic Risk Management: A Functional and Lifestyle Approach; Thomas Guilliams, Ph.D., 2018 • The Longevity Diet; Valter Longo, Ph.D., 2018 • Mitochondria in Health and Disease; Ray Griffiths, 2018 • Maimonides and Metabolism: Physiology of Fat Loss; Rabbi Yonason Herschlag, 2016