The Metabolic Code Weight Loss System for Life Time

Weight Loss Specialist Training

Copyright 2010 James B. LaValle, Integrative Health Resources, LLC. All rights reserved. No part of this material may be used or reproduced in any manner whatsoever, stored in a retrieval system, or transmitted in any form, or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission of the author. This material is provided for educational and informational purposes only to licensed health care professionals. This information is obtained from sources believed to be reliable, but its accuracy cannot be guaranteed. Herbs and other natural substances are very powerful and can occasionally cause dangerous allergic reactions in a small percentage of the population. Licensed health care professionals should rely on sound professional judgment when recommending herbs and natural medicines to specific individuals. Individual use of herbs and natural medicines should be supervised by an appropriate health care professional. The use of any specific product should always be in accordance with the manufacturer's directions.

Copyright 2009 James B. LaValle, Integrative Health Resources, LLC

Weight Loss - New Approaches Needed

Weight Loss - conventional approaches still focusing entirely on calories in- calories out and is . . . Not evaluating all the factors that can affect the equation. NIH - 2004 issued new strategic plan for obesity

NIH Obesity Plan

ID - behavioral and environmental causes of obesity Increase knowledge of molecular pathways of integrative body systems linked to obesity Elucidate role of macro and micronutrient effects on energy metabolism Elucidate role of brain regulatory and reward pathways on appetite. In other words - leave no stone unturned when it comes to obesity epidemic.

Metabolic Code Diet

Develop a weight management plan that will incorporate appropriate diet, exercise, lifestyle and, if indicated, appropriate and safe dietary supplements to support all metabolic needs.

Shifts in Endocrine Function and Regulation of Weight

Metabolic Effects of Insulin Resistance and Inammation

Hormones and Neurotransmitters

Adrenal

Inflammation
Insulin Resistance

Pancreas

Thyroid

Weight Management
Controlled by interplay of endocrine organs Function of organs Balance of hormones Outside inuences on hormones

Insulin Resistance
Cells no longer respond to insulin release Linked to chronic diseases: diabetes, heart disease, cancer, Alzheimers, high blood pressure and more Many causes - high carb diets, mineral deciencies, increased number of fat cells (resistin), low activity, hormonal inuences, inammation, environmental toxicity Triggers inammation chemistry

Inammation and IR
Non-diabetic women, CRP levels highest in those with highest fasting insulin Fasting insulin was also strongly associated with BMI and IL 6
Ridker PM, Pare G, Parker A, et al. Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. Am J Hum Genet. 2008 May;82(5):1185-92. Epub 2008 Apr 24.

Insulin Resistance Study

46,578 members of Kaiser Permanente Northwest FPG levels < 100 mg/dL (Jan 97-Dec 2000) No previous diagnosis of diabetes or impaired fasting glucose Subjects assigned to 1 of 4 categories (<85, 85-89, 90-94, or 95-99 mg/dL) Followed until developed diabetes, died, left the health plan, or until April 30, 2007 Cox regression analysis--estimated risk of incident diabetes, adjusted for age, sex, body mass index, blood pressure, lipids, smoking, cardiovascular disease, and hypertension

Study Results and Conclusions

Every glucose rise of 1 point above 84, was correlated with a 6% increase risk of developing Type 2 diabetes Insulin resistance, which leads to Type 2 diabetes, is developing at least a decade before detection by traditional lab markers
Nichols GA, Hiller TA, Brown JB. Normal Fasting Plasma Glucose and Risk of Type 2 Diabetes Diagnosis. Am J Med. 2008;121(6). 519-524.

Inammation and Diabetes

27,628 women free from diabetes and cardiovascular disease (Womens Health Study) 188 women developed diabetes over 4-year follow-up CRP and IL-6 strongly associated with development of diabetes Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inammation in diabetogenesis.
Pradhan AD, et al. JAMA 2001 Jul 18;286(3):327-34.

Zeyda M, Stulnig TM. Obesity, inflammation, and insulin resistance--a mini-review. Gerontology. 2009;55(4):379-86. Epub 2009 Apr 8. Review.

Insulin Action Whats Supposed to Happen

Glucose transport: A very involved process

Belly Fat Metabolic Activity

High insulin levels visceral (belly) fat storage Fat breakdown inhibited Produces pro-inammatory adipokines, including TNFalpha, IL-6, resistin Suppresses adiponectin, leptin, PPARs Visceral fat correlated to metabolic syndrome
Ceriello A. Metabolism. 2000;49(2 Suppl 1):27-9. Matsuzawa Y. Establishment of a concept of visceral fat syndrome and discovery of adiponectin. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(2):131-41.

Insulin Resistance (IR)

Prole of Client Exhibiting Signs of IR Elevated Waist-to-Hip ratio May or may not be overweight FPG 90 100 mg/dL or more Post-prandial insulin elevated. Lipids and trigs elevated with suboptimal HDL Elevated Blood Pressure

Insulin Resistance W/H ratio

Waist to hip ratio is one of strongest predictors of CV disease
Women > 0.8, Men >.95 = increased risk

Signs/Symptoms of IR
Lab Values - Fasting BS > 90, elevated triglycerides, elevated BP Elevated insulin response to carb load w/o elevated FPG Excessive thirst or hunger Eating calms or causes sleepiness Carbohydrate cravings Fatigue Brain fogginess Fluctuating energy levels Headache Weight gain especially belly fat Mood imbalances, agitation Low body temperature Low blood sugar; anxiety or irritability with missed meals (precursor to IR, shows glucose dysregulation))

Assessment Questions
Insulin Resistance 1. Do you have high triglycerides? Elevated triglycerides indicate either high fructose or alcohol intake, or blood sugars staying elevated. 2. Do you have high LDL cholesterol and low HDL? Cholesterol elevates when there are too many triglycerides being made (cholesterol fractions are used to transport lipids.) 3. Do you have an elevated waist to hip ratio? Elevated insulin promotes storage of weight in belly. 4. Is your diet high in sugar and/or trans fats? Excess consumption promotes inflammation and elevated blood glucose. 6. Is your blood pressure starting to elevate? (> 135/85?) Insulin resistance leads to BP incr. Elev BP means ins resistance is present. 7. Is your fasting blood sugar > 90 mg/dL. Blood glucose should return to optimum levels after eating.

Assessment Questions
Inflammation 1. Do you have an elevated waist to hip ratio? Any fat stored in waist produces inflammatory cytokines. 2. Do you eat very few fruits and vegetables? These foods are best sources of antioxidants. Low intakes create susceptibility to increased free radicals from environment and other sources. 3. Is your C-RP HS elevated? < 1 mg/L = low risk, 1- 2 mg/L avg risk, 3 mg/L high risk 4. Do you have indications of insulin resistance? Any positive answers on insulin resistance indicators means some inflammation is present. 5. Do you have chronic pain or inflammation?

Exercise and Insulin Resistance

Up to two hours after exercise, glucose uptake elevated due to insulin independent mechanisms - increased GLUT4 A single bout of exercise can increase insulin sensitivity for at least 16 h post exercise in healthy as well as Type 2 diabetics Acute exercise also enhances insulin stimulated GLUT4 translocation
Borqhouts LB, et al. Exercise and insulin sensitivity: A review. Int J Sports Med. 2000.21(1):112.

Exercise and Insulin Resistance

Human studies have reported that exercise: Improves insulin sensitivity Increases adiponectin levels Increases glucose transport Reduces body weight and fasting insulin Reduces postprandial insulin plasma levels Increases delayed release of glucagon-like peptide-1

References
Martins C, et al. The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat. J Clin Endocrinol Metab. 2010 Apr;95(4):1609-16. Koistinen HA and Zierath JR, Regulation of glucose transport in human skeletal muscle. Annals of Medicine. 2002. 34:410-417 van der Heiden GJ, et al. Aerobic exercise increases peripheral and hepatic insulin sensitivity in sedentary adolescents. J Clin Endocrinol Metab. 2009. Nov;94(11):4292-9. Epub 2009 Oct 6:684-91.

Exercise and Insulin Resistance

HIIT High Intensity Intermittant Training vs. Steady State Exercise More effective in improving fasting plasma insulin levels than steady state exercise Study: 15 wk. program, 2 groups of women, CV tness improvement in both groups, only HIIT group had decrease in TBM, fat mass, trunk fat, and FPG levels
Int Journal of Obesity (Lond). 2008; 32(4

Exercise and Nutrients

Regular intense exercise that induces sweating . . . Sweating - helps remove toxins Also lose nutrients - ie chromium excretion in urine increases with exercise. Magnesium and other trace minerals are excreted in sweat and urine.
Dunford and Doyle, Nutr in Sports and Exercise, 2008 Thomson and Wadsworth. Lukaski, H. Magnesium, chromium and zinc nutriture in physical activity. AJCN, 72;2:585S-93S. Aug. 2000.

Insulin Resistance and Overtraining-Underrecovered

Overtraining can lead to neuro-endocrine immune imbalance Increase in inammatory cytokines (TNF-alpha, IL-1, IL-6) Anabolic hormones (i.e. testosterone, growth hormone, IGF-1) and cortisol reported elevated during 15-30 of post-resistance exercise Associated with sleep and mood disturbances, inammation, immune imbalances, fatigue, IR Moderate, regular exercise actually improves anti-inammatory cytokine release

Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med. 2005;35(4):339-61. Review. Main LC, et al. Relationship between inammatory cytokines and self-report measures of training overload. Res Sports Med. 2010 Apr;18(2):12739. Astrom RE, et l. Persistent low-grade inammation and regular exercise. Front Biosci (Schol Ed). 2010 Jan 1;2:96-105.

Supplement Recommendations

Multivitamin/mineral support
A 2010 double blind, placebo controlled study followed 96 obese women (BMI > 28) for 28 weeks Patients receiving MultiVitamin/Mineral supplements reported: BMI Body weight Fat mass Blood pressure C-reactive protein Total cholesterol, LDL, HDL REE

Li Y, et al. Effects of multivitamin and mineral supplementation on adiposity,energy expenditure and lipid proles in obese Chinese women. Int J Obes (Lond). 2010 Feb 9. [Epub ahead of print]

Fish Oil
Omega 3 in sh oil known to : - Reduce inammation (decr TNF alpha, IL 1 and 6) - Help depression - Reduce triglycerides
Oh R. Practical applications of fish oil (-3 fatty acids) in primary care. Journal of the American Board of Family Practitioners 2005;18(1):28-36.

Life Time Omega 3 Fish Oil provides 1200 mg with optimum EPA 360mg and DHA 240 mg.

Life Time Supplements with Antioxidants

FastFuel Complete Menss andWomens multivitamins Lean Source Alpha Lipic Acid (Douglas)

LeanSource Weight Loss Supplement

Supports weight loss and metabolism, Formulated for training and exercise programs Helps improve insulin resistance and blood sugar regulation Hormonal regulation Improves thermogenesis

LeanSource Ingredients
LTFBiChrom Complex (Chromium picolinate and Chromium polynicotinate) 200mcg Clarinol CLA Complex 2000mg 7Keto 50mg Green Tea Extract (leaf, standardized to 45% EGCG and 90% polyphenols) 400mg Green Tea Extract (leaf, standardized to 50% polyphenols) 50mg American Ginseng (root) 300mg Eleuthero (root) 20mg

Douglas Products for IR

Alpha lipoic acid
Antioxidant nutrient Stimulates PGC-1alpha via C-AMP Kinase Keeps PPAR proteins from being damaged by oxidative stress Dose is 500-1000mg daily, sustained release
Weile S. et al. J Cell Biochem. 2008 Feb 7; : 18260126.

Supplements for IR
Douglas Labs Vitamin D-1000 IU or 5000 IU Supports healthy immune system Low vitamin D levels linked to MS and other disease linked to increased blood sugar and insulin resistance Women with low Vitamin D more prone to gain visceral fat Also linked to low testosterone in men and depression in men/women

Am J Clin Nutr. 2010 April 14 J Clin Endocrinol Metab 2009 Jan 94 (1):67-73. Epub 2008 Nov. 4

Magnesium
Magnesium - from NHANES 1999-2000 68% got less than RDA, 19% consumed less than 50%. Mg is required for ins action and proper glu utiization. Def is assoc with Tpe 2 diab and HTN. http://www.ncbi.nlm.nih.gov/pubmed/15319146 Low magnesium levels were associated with 1.48 to 1.75 times risk of increase CRP. Less than 50% RDA was associated with 2.24 times risk elevated CRP
JACN, Vol. 24, No. 3, 166-171 (2005)

Douglas CaMag 1001

Ingredients - Vit C, Vit D, Boron (trace mineral) enhance absorption - Equal ratio cal to mag, 500 mg ea.in mineral chelated forms

Other Metabolic Factors related to IR

Low thyroid Gut health Stress Hormones and Catecholamines Low Vitamin D Status Intoxication esp. pesticides Sex hormone imbalances

Stress (Adrenal) and Thyroid

Endocrine Function and Dysfunction and Regulation of Weight

Hormones and Neurotransmitters

Adrenal

Chronic Stress
Sustained Fight or Flight

Pancreas

Thyroid

What is Stress?
By-product of modern life--no longer Fight or Flight but sustained pressure Im having a bad day. Time commitments Financial stress Trafc Spiritual and emotional issues Family-Work-Environment Exercise Medical conditions Drugs Change

Potential Signs of Chronic Stress Chemistry

Insomnia-unable to fall asleep and/or waking in the middle of the night Less resistant to infection Lipid prole numbers creeping up Headaches Allergies Dizziness upon rising Excessive perspiration Cant recover from exercise Short term memory Food Craving patterns especially evening

Chronic Stress and Disease

Effects of stress hormones are systemic An estimated 85 percent of diseases have stress related factors Important factor in Metabolic Syndrome and insulin resistance and therefore weight control

Metab 47(12), Dec. 1998; 1440-9 Metab 45(3), 1996; 351-6. Gynecol Endocrin 8, 1994; 247-254.

Three Stages of Stress

1. 2. Alarm Activated by acute stress Massive release of catecholamines (epinephrine and norepinephrine) from adrenal medulla Resistance Chronic, intense ongoing stress Hypothalmus signal pituitary to release ACTH ACTH stimulates adrenal cortex: release various steroid compounds Exhaustion Depletion of reserves, illness, disease and death Body can no longer adapt to effects of stress

3.

Effects of Chronic Cortisol Elevation

Insulin secretion and IR Fat deposition (belly fat) in immune regulation Muscle wasting Hypothyroidism Alterations in neurotransmitters Oxidative stress Cognition Bone loss Sodium and water retention Elevated blood lipids REM sleep Regulation of in sex hormones Retards regeneration of connective tissue, slow wound healing

Stress and Thyroid Function

Adrenal and thyroid function closely linked Under control of hypothalamus and tropic hormones Thyroid competes with adrenals for tyrosine.

Stress and Thyroid Function

Increased cortisol levels inhibit conversion of T4 to T3 and favors conversion to rT3 secondary to diversion of tyrosine to cortisol production vs. thyroid hormone production rT3 decreases cellular energy production Increases in T3 reverse this decline
(Okamoto R et al. Adverse effects of reverse triiodothyronine on cellular metabolism as assessed by 1H and 31P NMR spectroscopy. Res Exp Med (Berl) 1997;197(4):211-7)

Thyroid and Metabolism

Thyroid hormone increases # of mitochondria Thyroid hormone inuences rate of ATP production in mitochondria Thyroid hormone increases the uptake of oxygen by the cells Diminished secretion of thyroid hormone reduces metabolic capacity up to 40 percent

Takashima N et al. Characterization of subclinical thyroid dysfunction from cardiovascular and metabolic viewpoints. Circ J. 2007 Feb;71(2):191-5.

Far- Reaching Thyroid

T3 modulates gene transcription Thyroid hormones regulate myocardial gene expression/ increases myocardial sarcoplasmic reticulum Ca2+-ATPase Cardiac pace making Neuroreceptor expression and development Vasodilation of smooth muscle. Stimulate the production of bile acids from cholesterol Effects HCl production

Metabolic Effects of Suboptimal Thyroid Function

Glucose tolerance
Thyroid hormone inuences the rate at which glucose is absorbed from the GI tract and taken up by cells

Insulin resistance
Hypothyroidism reduces target cell insulin binding/number of insulin receptor expressed

Metabolic Effects of Suboptimal Thyroid Function

Cardiovascular health
Decreases metabolism of fats and increases serum lipids Decreases the availability of cardioprotective essential fatty acids Inadequate T3 lowers oxygen consumption, contributes to lipids peroxidation and free radical damage (J Clin Endocrin
Metal, 82 (10) Oct. 1997)

Subclinical hypothyroidism an independent risk factor in atherosclerosis and myocardial infarction (Ann Intern Med 132 (4)
Feb 15, 2000)

The Headlines
Stress/obesity linked Stress and belly fat linked Stress and insomnia linked Sleep deprivation/weight gain linked

CortisoBelly Fat Linked

Study nding: Cortisol stimulates enzyme in fat cells, increases visceral fat storage
(Epel E, et al. Can stress shape your body? Consistently greater stress-induced cortisol secretion among women with abdominal fat. Psychosomatic Medicine, 2000 (62); 623-632.)

Stress/Obesity Link
Study symptoms of depression, anxiety, sleep disturbances, psychosomatic illness, and life satisfaction are positively correlated with an increased waist to hip ratio (belly fat)

Rosmond, R. et al. Mental distress, obesity, and body fat distribution in middle aged men. Obes Res. 1996 May;4(3):245-52

Sleep Deprivation/Elevated Stress Hormones Linked

First controlled study to demonstrate that chronic insomnia leads to increased ACTH and Cortisol levels. Hormonal data suggest insomnia is a disorder of hyperarousal. Study authors suggested that down regulation of HPA axis is the most promising approach for insomnia
(J Clin Endocrin Metab 2001 Aug 86 (8); 3787-94)

Sleep Deprivation and Weight Gain Linked

Subjects that avg. 4 hr. sleep/night: Leptin (18%), Ghrelin (28%) reported hunger (24%), carb cravings, especially sweets, salty, and starchy high calorie snacks (Ann Intern Med, 2004, vol.141, pp.846850) > 1,000 volunteers: those that avg. , 5 hr sleep had leptin (15.5%), ghrelin (14.9%), BMI (3.6%). Results were regardless of the subjects diet and exercise habits. (Mignot et al, Stanford School of Medicine Dec. 2004)

Sleep Deprivation/Weight Gain Linked

Heymseld and Gangwisch analyzed NHANES I data: Found that subjects with avg. 5hr./night sleep had 73% increased likelihood of obesity over those who slept 7-9 hr/night. ( Findings reported at the annual scientic meeting of the North
American Society for the Study of Obesity. Nov, 2004)

Study showed a linear relationship: reduced amounts of sleep are associated with overweight and obesity (Arch. Intern
Med, 2005;165:25-30)

Sleep Decits
Chronic partial sleep loss associated with decreased glucose tolerance, decreased leptin levels, increases in evening cortisol levels, adverse cardiovascular events Lack of sleep increases heart attack risk and development of arterial plaques
Spiegel et al. Lancet 1999 354; 1435-39. Spiegel et al. J Clin Endocrin Metab 2004, 89(11);5762-71. Taylor DJ, et al. Sleep. 2007;30(2):213-18 Kapsimalis F, et. al. Sleep Med. 2007 Nov 15 [Epub ahead of print]

Sleep
During sleep - we repair and restore body tissues Blood pressure drops Energy stores build up Growth Hormone is released during sleep

Insomnia or Disrupted Sleep

Alters Growth Hormone release Increases TNF alpha, IL-6 Increases insulin resistance Contributes to weight gain Increases TBG

Stress, BMI and Free Radicals

Increased free radicals-cause cellular damage Increased BMI linked to increased markers of inammation
Arterioscl, Thromb, and Vasc Bio 2003;23:434-493 Juge-Aubrey, CE, et al. Diabetes May 2003 (52); 1104-10.

Stress and Sleep Deprivation

Elevated cortisol decreases serotonin and melatonin Also causes PM blood glucose alterations Elevated evening cortisol disrupts sleep and is the primary cause of insomnia Sleep disturbances
Inability to turn off the day Waking in the middle of the night

Stress and Cognitive Function

cortisoDHEA ratio correlated to short term memory loss cortisol intracellular Ca, oxidative stress, inammatory cytokines, mitochondrial function cell death = hippocampus atrophy Net result: short memory loss, mood disorders, neurological disorders, sleep deprivation

Studies
Decits in hippocampus mediated Pavlovian conditioning with endogenous Hypercortisolism Grillon, C et al Biol Psychiatry, 2004 Dec 1:56(11) 837-843 Young AH, Gallagher, Porter RJ Elevation of cortisol-DHEA ration in drug free patients Am J Psychiatry 2002 July:159(7) 1237.9 Relationship between Cortisol and DHEA sulphate and IGF-1 system in dementia Muriado G, etal J Endocrinlogic Inves 2001March 24(3) 139-146

Assessing Adrenal Function

4 Point Salivary Cortisol (dont assume a flat cortisol response means adrenal fatigue Serum Cortisol 8 a.m. DHEA Serum or Salivary Sodium

Adrenal Questions
1. Do you sleep at least 7 or 8 hours per night? 2. Are you under high stress from personal or work-related stress or from being overcommitted in your life? 3. Do you have dark circles under your eyes? 4. Do you crave sugars or carbohydrates in the afternoon and evening? 5. Do you feel tired and wired? 6. Do you have trouble falling asleep or staying asleep? 7. Do you often have a midday crash in energy? 8. Do you feel anxious or nervous? 9. Are you easily irritated, or snap easily at family or co-workers?

Exercise for Stress-related Weight Control

Set goals to increase motivation Use stress-control as a motivation Yoga is one of the best modalities of exercise to reduce stress levels Yoga can result in weight loss void of other lifestyle and dietary changes Moderate exercise is key to prevent exercise-induced stress

Smith C et al. Complement. Ther. Med. 2007;15(2):77-83 West J, Ann Behav Med. 2004;28(2):114-8 Gill JM. Health News. 2005;11(10):14

Stress, Sleep, Ins. Resistance

Signs of insulin resistance, evaluate stress levels If report multiple chronic stress signs , suggest stress management techniques, counseling, better time management, meditation, yoga, and/or supplement support If person cant sleep, down regulate daytime stress response

Relora
Proprietary blend of Magnolia ofcinalis and Phellodendron amurense Marketed for stress-related appetite control and reduction of stress-related fat deposition

Relora
Anti-anxiety and anti-stress properties rival benzodiazapenes, yet non-sedating Anti-depressant properties Normalizes cortisol and DHEA levels Low side-effect prole

Relora
Unpublished human trial results: 250 mg TID for two weeks 50 subjects 227% increase in salivary DHEA 37% reduction in morning salivary cortisol

Relora
78% reported feeling relaxed 94% reported no GI complaints Safety eval - toxicity study in animals found that doses as high as 5g/kg yielded only mild side effects

Life Time Supplements for Stress

Douglas Labs Relora-Plex 2 capsules contain Relora: 500 mg Vitamin B1: 10 mg Vitamin B2: 10 mg Niacinamide: 10 mg Vitamin B6: 10 mg Vitamin B12: 100 mcg Folic Acid: 200 mcg

Magnesium
In animals and humans - stress brings on sudden inux of calcium into cells, this can bring on hypertension and heart arrhythmia. Magnesium block stress response by blocking the calcium channels.
Levin, R.M., et al. (1976). Biochem Pharmacol 25(17): 1963-9. Shimosawa, T.K, et al. (2004). Hypertension 44(6): 897-902.
Steinberg, J. S.,et al. (2004). Increased incidence of life-threatening ventricular arrhythmias in implantable debrillator patients after the World Trade Center attack. JAmCollCardiol 44(6): 12611264.

Other Stress/Sleep Support

5 Hydroxytryptophan (5-HTP)
Precursor to serotonin Inuences the synthesis of melatonin Serotonin is the neurotransmitter that regulates sleep, mood, satiety, and even pain tolerance. Stress leads to signicant loss of serotonin When serotonin levels are low, it can lead to carbohydrate cravings. Dosage Range: 25-300mg

Other Sleep - Melatonin

Potent antioxidant Relieves symptoms of jet lag May adversely affect sleep patterns with headaches, slowed reaction time, nightmares, or mild depression Caution in use with autoimmune disorders Dosage: Melatonin (99.6% pure) 3-18mg at bedtime for insomnia

Thyroid Questions
1. Do you feel tired from morning to night? 2. Do you have extreme difficulty losing weight? 3. Do you have a lot of trouble getting up in the morning? 4. Do you have cold hands and feet? 5. Are you constipated? 6. Do your muscles feel weak? 7. Do you struggle with depression or low mood? 8. Do you have thin hair or lose a lot of hair with brushing and shampooing? 9. Do you have swollen upper eyelids?

Gut Health
Intestinal Influences on Weight Gain

Gut Function
Primary function - digestion and absorption of nutrients while maintaining a barrier between intestinal contents and blood stream Immunity - houses 70% of immune system - gut associated lymphoid tissue (GALT), secretory IgA and other immunoglobulins produced in gut Flora - number 1014 , over 400 species, aid digestion and immunity, key to many gut fxs, ie teach immune cells which antigens are harmful and regs permeability of gut Peptides/hormones made in gut aid insulin, alter pancreas to presence of glucose, affect blood sugar and appetite regulation

Intestinal Permeability
Dependent on the regulation of intercellular tight junctions Made from multiple proteins inc. occludin, claudins, junction adhesion molecule (JAM) Form a selective seal of the intracellular space-regulates passage of ions and molecules through the paracellular space Must have rapid response due to diverse challenges epithelial barrier is subjected to. TNF, INF and nitric oxide trigger dysfunction

Intestinal Permeability-Zonulin
Zonulin-reversibly modulates tight junction permeability Protects proximal intestine from colonization of microbes (innate immunity) Regulates fluid, macromolecules, & leukocytes from intestinal lumen to blood stream and vice versa. The gatekeeper of the gut, allows some substances through while not allowing others Upregulation is associated with increased permeability

Intestinal Permeability, Gliadin and Autoimmunity

Intestinal cells of both celiac and non-celiac patients exhibited increased permeability when exposed to gliadin Chronic gliadin exposure resulted in down-regulation of both ZO-1 (zonula occludens-1) and occludin gene expression. Loss of the protective function of mucosal barriers is a key element necessary to develop autoimmunity (in gastrointestinal and lung mucosa).
Drago S, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19. Curr Opin Gastroenterol. 2006;22(6):674-679

Probiotics
Hold down inflammation via proper immune cell response to antigens Up-regulate beneficial IgA-prevent allergies, inflammation and disease Produce SCFAs (like butyrate)
fuel for intestinal cells mucus production of goblet cells-prevents lectins from nuts, seeds, legumes and grains (wheat agglutinin) from damaging mucosal lining Promote proper pH of intestines (slightly acidic)yeast control

Probiotics
Improve mucosal barrier function - suppress growth and invasion of pathogens Prevent apoptosis of epithelial cells Prevent antibiotic associated diarrhea Decreases childhood gastroenteritis Increases lactose digestion
Eur J Nutr 2006 45, Suppl 1; 1-18.

Probiotics
Increase production of anti-inflammatory cytokines Decrease pro-inflammatory cytokines

ASPEN Guidelines on Enteral Nutrition Clinical Nutr Jan 2006

Probiotics and SCFA

Probiotics - beneficial gut flora, different strains being IDd for different effects Butyrate - short chain fatty acid produced by probiotics increases gut mucosa cell proliferation decreases apoptosis of intestinal cells keeps immune system activity in check/prevents overactivity

Probiotics and Propionic Acid

SCFA-Propionic acid (PA) created by fermentation of dietary fiber in the intestine PA stimulated leptin mRNA expression and secretion by OAT and SAT PA reduced pro-inflammatory resistin mRNA expression May explain dietary fibers protective role in obesity, insulin resistance and type 2 diabetes

Al-Lahham, S. et al, Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest 2010; 40 (5): 401407

Strain Specific Functions

L plantarum (3 strains of) and 2 strains of L paracasei found to control C. Diff (Med Microbiol 2004;53:551 and L GG - improves gut barrier function S thermophilus and L acidophilus - enhance tight junction proteins and can prevent E coli (World J Gastroenterol Oct 7,2006; 12(37):5941-5950. L plantarum reduced systemic inflammation response (Clin Nutr Apr.2005, 24(2):211-214)

Factors Influencing Intestinal Flora and Gut Integrity

Antibiotics OCs/HRT Radiation/chemo Corticosteroids NSAIDs Sugar in the diet Bactericidal chemicals in drinking water
Pesticides in food Alcohol Heavy metals H. pylori Gastrointestinal pH Stress Bowel transit time

Factors Leading to Bowel Dysfunction

Change in beneficial flora due to ABX High stress + increased cortisol = hypochloria and poor digestion reduced IgA production Poor diet high in sugar, refined flours, alcohol, processed foods Yeast overgrowth (Candidiasis) as probiotics die out yeast multiplies Decrease in gut enzymes (amount and potency) = poor digestions and nutrient absorption

Antibiotics and Gut Health

Can wipe out gut flora-dependent on dosage, length of administration Studies show profound effects that can last for months Yeast overgrowth occurs when good bacteria are lacking
Nord CE, Edlund C. J Chemother. 1990;2:218-237 Sullivan A. Lancet Infect Dis. Sept 2001.1(2):101-114.

Effects of Yeast on the Gut

Ferments ingested sugars and starches creating gas and bloating after meals Puts out mycotoxins which can: Damage and destroy intestinal cells Dampen immune response of T cells in the gut, preventing normal food substances recognition. Crowds out good bacteria which direct production of tight junction proteins Produces acetaldehyde which can interfere with mood, mental clarity and can lead to chemical sensitivities.

Yeast and the Endocrine System

Yeast toxins have a particular affinity for the endocrine organs Receptors for both estrogen and corticosteroids, identical to human receptor sites identified on the cell wall of Candida albicans Create hormone masking and mimicry Disrupt the negative feedback to the pituitary

Dietary Link to Yeast Overgrowth

Women who had increased urinary sugar levels were more prone to vaginal yeast infections. Higher urinary sugar levels were linked to higher sugar and dairy intake (perhaps secondary to ABX residues)

Horowitz BJ, et al. J Reprod Med. 1984;29:441-3

Antibiotics from Food Sources

Antibiotics used in feedlot animals - cause weight gain in animals. (Antibiotics may cause weight gain in humans.) Antibiotics used in dairy cattle for infections, enter the milk or foods made with it (non-organic milk.) Enter those who drink the milk/consume foods, enough to shift gut flora. Both uses increase the problem of antibiotic resistance.

Effects of Flora Shift

Can lead to immune shifts/incr infl Immune shifts can result in food allergies and eventually to autoimmunity (e.g. Hashimotos thyroiditis). Food allergies can also cause food cravings and unbalanced eating habits. Lack of beneficial flora and yeast overgrowth in gut can greatly reduce nutrient absorption, many of which are key to weight management.

Bowel Dysfunction
Dysbiosis

Leaky Gut

Food allergies

Definition of Leaky Gut

Loss of tight junction proteins Destruction of mucosal barrier Influenced by medications, antibiotics, NSAIDS

Calderone et al., Med Mycol 38 (suppl 1 ) 2000; 125-37.

Allergenic Proteins and Immune Response

Lack of probiotic colonization in the gut results in immune cell activation Pro-inflammatory cytokines Immune cells mature into antibodies, IgG, IgA, IgE that also produce inflammatory cytokines Inflammatory cytokines = inflammation, contribute to accelerated aging process and chronic disease
Ghoshal UC, Ghoshal U. Trop Gastroenterol. 2007;28(2):43-4

Food Allergies and Intolerances

Food allergies trigger immune cell production of inflammatory substances - internal inflammation damages insulin receptors and cause insulin resistance, a primary cause of weight gain. Stress hormones can shift gut flora leading to gut flora imbalance and the problems that follow. Food allergies can incr stress hormones production- can contribute to insulin resistance and midsection weight gain or belly fat.

Stadnyk AW. Intestinal epithelial cells as a source of inflammatory cytokines and chemokines. Can J Gastroenterol. 2002;16(4):241-6. Keltikangas-Jarvinen L, Ravaja N, Raikkonen K, et al. Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress. Metabolism. 1998 Dec;47(12):1440-9.

Food Allergies- References

Ramagopalan SV, et al. Childhood cow's milk allergy and the risk of multiple sclerosis: a population based study. J Neurol Sci. 2010 Apr 15;291(1-2):86-8. Epub 2010 Jan 21. Michels AW, et al. Immunologic endocrine disorders. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S226-37. Visness CM, et al. Association of obesity with IgE levels and allergy symptoms in children and adolescents: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2009 May;123(5):1163-9, 1169.e1-4. Epub 2009 Feb 23. Resta SC. Effects of probiotics and commensals on intestinal epithelial physiology: implications for nutrient handling. J Physiol. 2009 Sep 1;587(Pt 17):4169-74. Epub 2009 Jul 13. Review.

Mercury in the Intestines

Ingested or inhaled mercury inhibits neutrophils and their subsequent TH1 and TH2 cytokine effects which control Candida. Lowered neutrophil activity allows proliferation of candida. Candida organisms methylate mercury vapor from the mouth in the intestines and the mouth. Candida albicans may trap mercury. Candida albicans and its mycotoxins are associated with chronic fatigue and autoimmune disorders.

Mercury and Candida References

M.L.S.Queiroz et al, "Immunoglobulin Levels in Workers Exposed to Inorganic Mercury", Pharmacol Toxicol 74:72-75, 1994; & "Presence of Micronuclei in lymphocytes of mercury exposed workers', Immunopharmacol Immunotoxicol, 1999, 21(1):141-50; & D.C.Santos, "Immunoglubuline E in mercury exposed workers", 1997, 19(3):383-92.. S. Yannai et al, "Transformationss of inorganic mercury by candida albicans and saccharomyces cerevisiae", Applied Envir Microbiology,1991, 7:245-247 B.J. Shenker et al, Dept. Of Pathology,Univ. Of Penn. School of Dental Med.,"Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes:Alterations in cell viability" and "Immune suppression of human T-cell activation", Immunopharmacologicol Immunotoxical, 1992, 14(3):555-77 P.E. Bigazzi, "Autoimmunity and Heavy Metals", Lupus, 1994; 3: 449-453. (235) H.J.Hamre, Mercury from Dental Amalgam and Chronic Fatigue Syndrome", The CFIDS Chronicle, Fall 1994, p44-47. M. E. Godfrey, Candida, Dysbiosis and Amalgam. J. Adv. Med. vol 9 no 2 (1996); & Romani L, Immunity to Candida Albicans: Th1,Th2 cells and beyond. Curr Opin Microbiol 1999, 2(4):363-7

Food Allergies and Intolerances-Symptoms

Seasonal (environmental) allergies Headaches Joint and other arthritis pain Autoimmune conditions Thyroid problems Metabolic imbalances incl. difficulty losing weight

Arroyave Hernndez CM, Echevarra Pinto M, Hernndez Montiel HL. Food allergy mediated by IgG antibodies associated with migraine in adults. Rev Alerg Mex. 2007 Sep-Oct;54(5):162-8. Kitts D, Yuan Y, Joneja J, Scott F, Szilagyi A, Amiot J, Zarkadas M. Adverse reactions to food constituents: allergy, intolerance, and autoimmunity. Can J Physiol Pharmacol. 1997 Apr;75(4):241-54. Review.

Allergenic Foods
7 foods make up 90% of food allergies - Peanuts/Walnuts - Shellfish - Wheat - Cows milk - Eggs - Soy - Yeast Food Rotation Diets help prevent food allergies and are strongly encouraged by LMI

Assessment Questions
1. Do you have seasonal allergies?
2. 3. 4. 5. 6. Do you often feel mentally foggy? Do you often get bloated and gassy, especially after eating? Do you have chronic sinusitis? Do you have trouble with constipation or diarrhea? Do you have a history of taking antibiotics, birth control pills, NSAIDS or steroids? 7. Do you unexplained chronic conditions, ie headache, joint pain, or depression? 8. Do you eczema or other skin rash problems?

Supplements for Optimal Gut Health Probiotic

L-glutamine IgG powder Grapefruit seed extract Cats claw Vitamin D High mucin sialic adic Zinc carnosine Moducare Rhodiola or Relora for improved stress response

Potential Testing
Simple test is elimination diet. Labs tests: OAT test Comprehensive Digestive Stool (DNA) Allergy Panel IgG and IgE Gluten and Gliadin antibodies ANA, TNF alpha, IL6

Supplements for Optimal Gut Health

Douglas Labs Multi-probiotic 4000 Lactobacillus acidophillus: 1.5 Billion CFU L. Rhamnosus: 1.5 Billion CFU L. Rhamnosus (Type B, Bifidus): 775 Million CFU S. Lactis: 275 Million CFU Bifidobacterium Longum: 275 Million CFU B. Bifidum: 275 Million CFU S. Thermophilus: 150 Million CFU Proprietary Blend: 215 mg FOS (fructooligosaccharides) and ulmus fulva (inner bark)

Supplements for Optimal Gut Health

Douglas Labs Multi-probiotic 4000 Restore beneficial bacteria in the gut Antagonize bad bacteria and yeast Regulate immune responses

Dethelfesen L, et al. PLoS Biol. Nv 2008; 6(11):2383-2400 Pusztai A. et al. Bt J Nutr. 1993 Jul;70(1):313-1 Jordinson, M, et. al. Am J Phsiol. Apr 1996:270 (4 Pt 1):G653-59

Supplements for Optimal Gut Health

Douglas Labs Multi-probiotic 4000 Help with food allergies Inhibit fungal colonization of the GI tract which leads to improved gut health

Ponzio G, et al. Cell Signal. 1990;2(4):377-86 Logan AC and Kataman M. 2004 Med Hypothesis. 64:533-538

Supplements for Optimal Gut Health

FastFuel Complete Ingredients Dietary Fiber from Sunfiber (5 g)
gut fermentation of fiber produces SCFAs

Protein: 30 g
Builds and repairs intestinal tissue

Proprietary Fruit and Vegetable Blend: 750 mg

Antioxidants support against cellular damage

Supplements for Optimal Gut Health

FastFuel Complete Ingredients (cont.) Proprietary Digestive Enzyme Blend: 30 mg Supports proper digestion L-Glutamine: 2000 mg Source of energy for intestinal cells Supports digestive tract repair

Alander T. BMC Med. 2005 May 13;3-8

Supplements for Optimal Gut Health

Douglas Labs Vitamin D-1000 IU or 5000 IU Supports healthy immune system Low vitamin D levels linked to MS and other disease linked to increased blood sugar and insulin resistance Women with low Vitamin D more prone to gain visceral fat Also linked to low testosterone in men and depression in men/women

Am J Clin Nutr. 2010 April 14 J Clin Endocrinol Metab 2009 Jan 94 (1):67-73. Epub 2008 Nov. 4

Supplements for Optimal Gut Health

Douglax Labs Relora-Plex
Proprietary blend of Magnolia officinalis and Phellodendron amurense Marketed for stress-related appetite control and reduction of stress-related fat deposition

Supplements for Optimal Gut Health

Douglas Labs Relora-Plex
Anti-anxiety and anti-stress properties rival benzodiazapenes, yet non-sedating Anti-depressant properties Normalizes cortisol and DHEA levels Low side-effect profile

Detoxication

Our Toxic Environment

We are exposed to thousands of man-made toxins every day Studies have identied as many as 300 foreign chemicals, including several known carcinogens in the human body

National Human Adipose Tissue Survey http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=55204; Accessed April 15, 2010.

Xenoestrogens
Herbicides & Pesticides Solvents & adhesives Glues Fingernail polish Petrochemicals Emulsiers in soap Cosmetics

Xenoestrogens
Plastics containing BPA PCB (polychlorinated biphenals) Dioxins Meat & Milk Birth control pills Tap water Car Exhaust

Why are Heavy Metals Dangerous?

Bind sulfur groups on amino acids methionine, glutathione, cysteine Interfere with hundreds of chemical reactions Body cant detoxify

Bisphenol A (BPA)
BisphenolA (BPA)- production of polycarbonate plastics and epoxy resins, found in plastic food and drink containers. Over the past decade, more than 130 studies have linked the chemical to breast cancer, obesity, and other disorders. Endocrine disruptor

Environmental Toxins and IR

Pesticides, BPA associated with increased risk for IR Heavy metals also associated with increased oxidative stress and inammatory response Note - 90% of the pesticides in use today are used in the production of food

Ropero AB, et al. Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl. 2008 Apr;31(2):194-200. Galanis A, Karapetsas A, Sandaltzopoulos R. Metal-induced carcinogenesis, oxidative stress and hypoxia signalling. Mutat Res. 2008 Oct 30.Lee DH, et al. Diabetologia. 2007 Sep;50(9):1841-51.

Toxins and Weight

Several pesticides have been proven to disrupt thyroid hormones Toxic metals promote free radical production in the body; free radicals contribute to IR and weight gain Toxins increase inammatory chemicals; Inammation is linked to weight gain
Pelletier C, Imbeault P, Tremblay A. Energy balance and pollution by organochlorines and polychlorinated biphenyls. Obes Rev. 2003 Feb;4(1):17-24. Ruzzin J, Petersen R, Meugnier E, et al. Persistent organic pollutant exposure leads to insulin resistance syndrome. Environ Health Perspect. 2010 Apr;118(4):465-71. Epub 2009 Nov 19. Melov S. Mitochondrial oxidative stress. Physiologic consequences and potential for a role in aging. Ann N Y Acad Sci. 2000 Jun;908:219-25. Review.

Toxins and Weight

National Health and Nutrition Examination Study, 19992002 Prevalence of DM strongly positively associated with serum concentration of pollutants. Indivs in highest category of exposure (>90 percentile) had prevalence of DM 38X higher than lowest category

Lee DH, Lee et al. DiabetesCare 2006;29:1638-1644.

ADHD and Pesticides

Groundbreaking Study Cross Sectional Data on 1139 children aged 8 to 15 from 2000-2004 NHNES The most commonly detected pesticide metabolite, dimethyl thiophosphate, those with levels higher than the median had nearly twice the odd of ADHD Diet major source of pesticide exposure for children

Pediatrics. Published online May 17, 2010

Organs of Detoxication
Liver Bowel Skin Lungs Kidneys Lymph

Liver Detoxication-Phase I Oxidation and Reduction

Converts toxins to water-soluble compounds so that they can be excreted in the urine Network of enzymes known as cytochrome P450 Oxidation is the process of inactivating molecules through the transfer of oxygen and subsequent loss of electrons

Liver Detoxication-Phase I Oxidation and Reduction

Oxidation generates free radicals within the liver. Therefore, the liver must have a continuous supply of antioxidants. Compromised phase I detoxication are known as slow detoxiers

Causes of Slow Phase 1 Detoxication

Fasting Low protein diet Hydrogenated fats Age Iron overload Grapefruit juice Some prescription drugs

Liver Detoxication-Phase II Conjugation and Elimination

Substances needed for Phase II pathways: Sulfur compounds AAs glutathione, methionine and cysteine Glucuronic acid Acetyl CoA

Substances that Inhibit Phase II:

NSAIDs Low protein diet Nutrient deciencies
folic acid magnesium selenium B vitamins Zinc

Detoxiation and NutrientsGlutathione

Glutathione is vital to liver detoxication Helps to eliminate mercury and other fat soluble, toxic heavy metals Selenium is an essential trace mineral needed to make glutathione peroxidase

Detox and Exercise

Sweating aids detoxication Exercise helps to increase the rate of blood ltration and toxin removal When fat is burned, toxins stored in fat are released. The more you sweat, the greater potential for toxin removal, however if detox pathways are not running efciently toxins can stop metab again via IR and decr thyroid activity.

Toxin Burden Assessment

Do you have extreme difculty losing more than 10 pounds? Do you have chemical sensitivities such as intolerances to fragrances? Do you have chronic unexplained headaches, muscle pain and/or fatigue? Do you live in a heavily industrialized area, or live near a factory, or farms that use chemical fertilizers or pesticides? Do you have allergies or asthma?

Supplements to Support Liver Detox

Womens and Mens Performance Multivitamin (AM/PM)
Contains powerful antioxidants, minerals and whole foods including Vitamin C - Powerful antioxidant, protects against DNA damage, supports glutathione production Vitamin E Powerful antioxidant Selenium Trace mineral needed to make glutathione peroxidase. Displaces mercury.

Supplements to Support Liver Detox

Womens and Mens Performance Multivitamin (AM/PM) (cont.)
Mixed Vegetable and Fruit Complexes Sulforaphane from broccoli, cauliower, cabbage, Brussels sprouts supports Phase II detox Calcium D-glucarate from apples, Brussels sprouts, broccoli and cabbage protects intestinal breakdown of glucuronic acid conjugates and allows elimination via stool

Supplements to Support Liver Detox

Womens and Mens Performance Multivitamin (AM/PM) (cont.)
DIM (Diindolylmethane) from cruciferous vegetables promotes healthy estrogen metabolism Chelated Minerals magnesium, zinc, copper, manganese, molybdenum grab and remove heavy metals B-vitamins including folic acid important methyl donors

Supplements to Support Liver Detox

Douglas Labs Alpha Lipoic Acid
Powerful antioxidant Supports detox enzyme function Reduces toxic mercury exposure in the brain Detoxes cadmium from cigarette smoke and fuel exhaust

Petersen Shay K, et al. IUBMB Life. 2008; [Epub ahead of print] Smith AR, et al. Curr Med Chem. 2004;11(9):1135-46

Supplements to Support Liver Detox

Ultra-D Tox
Bentonite Powder, Psyllium Powder,Lactobacillus acidophilus(minimum of 1 Billion CFU), Garlic (deoderized), Celery Powder, Aloe Vera Powder, Prune Concentrate, Mint, Flax Seed Powder, Barley, Chlorella, Anise, Vitamin C, Bromelain and Magnesium Citrate

Supplements to Support Liver Detox

Ultra-D Tox (cont.)
Garlic One of the most widely studied natural compounds Increases Glutathione Acts as metal chelator Anti-viral properties imp. for complete removal of metal (some metals harbored within underlying viral and bacterial infections) Has antioxidant/anti-inammatory actions

Supplements to Support Liver Detox

Ultra-D Tox (cont.)
Chlorella A single-cell, fresh water algae that is rich in protein, chlorophyll, essential fatty acids, vitamins, and minerals. Detoxies mercury, lead, cadmium, as well as dioxin, PCBs and uranium.

Kay RA Crit Rev Food Sci Nutr 1991;30(6):555-73. Horikoshi, T., et al. Uptake of uranium by various cell fractions of Chlorella regularis. Radioisotopes 1979 Aug; 28(8): 4858. Singh A, et al. Anticancer Res 1999 May-Jun;19(3A):1887-91

Reducing Toxicity with Foods

First stop adding to the problem Compared to kids on organic diets, conventional diet kids had 6x higher levels of organophosphate pesticides

Curl et al. Environmental Health Perspectives, Volume 111 (2003): pages 377-382.

Organic Foods
Study of school age children. Substitution of organic foods immediately lowered organophosphate pesticide metabolites in urine to non-detectable levels. Metabolites remained nondetectable until conventional foods were reintroduced.
Chenseng L, et al. Environ Health Perspec 114:260-263 (2006).

ABX/Hormones/Pesticides
Beef - growth hormones, antibiotics, pesticides on feed concentrate in fat Poultry - pesticides concentrate in fat Dairy - growth hormones, antibiotics, pesticides Eggs - pesticides Pork pesticides

Dirty Dozen
www.ewg.org
Celery Peaches Strawberries Apples Blueberries Nectarines

- Bell Peppers
- Spinach - Kale - Cherries - Potatoes - Grapes (imported)

Metabolism and Nutrient Deciencies

Reasons for Functional Nutrient Deciencies

Diet - low consumption of nutr dense foods Lower nutrient density of foods Drug Therapy Exercise Genetics Stress Disease or Condition Specific situations

Nutrients in Foods Declining

From 1950s to 1999 protein, calcium, phosphorus, iron, riboavin, and vitamin C all declined in 43 garden crops Due to high yield crops, gradual depletion of soil micronutrients and organic matter, and changes in pest complexes and levels

Mayer, Brit Food J 99(6), 1997 Davis, J Am Col Nutr 23(6), Dec. 2005.

More Nutrients Needed?

U.S. intake - kcals 1970 = 2300 /day, yr 2000 = 2800/day (USDA Agriculture Factbook 2001-2002) Grains - avg intake of ours 200 lb/yr/person. Only 7% eating 3 whole grains servings/day. 2005 CDC survey 27% getting 3 veg/day, 33% ate 2 fruit/day.

Adequate Individual Nutrients?

Nutrients of concern for:
Adults - calcium, potassium, ber, vitamin A (carotenoids), vit. C, and E Adolescents and children- calcium, potassium, ber, magnesium, vit. E Adults > 50 yr. - B12, vit. D Childbearing - folate, iron
2005 USDA Dietary Guidelines for Americans.

Fruit and Vegetable Consumption

USDA recommends 9 servings per day (3 to 5 vegs, 2 to 4 fruits.) Americans - < 20% consuming 5/day Consuming too many rened ours, over processed foods So, despite increase kcal, there is a nutrition gap.

Produce for Better Health Foundation. State of the Plate: Study on Americas Consumption of Fruits and Vegetables, 2003, NPD National Eating Trends.

Are Americans Getting the RDAs for Nutrients?

Magnesium - from NHANES 1999-2000 68% consumed less than RDA, 19% consumed less than 50%. Low magnesium levels were associated with 1.48 to 1.75 times risk of increase CRP.

Less 50% RDA was associated with 2.24 times risk elevated CRP JACN, Vol. 24, No. 3, 166-171 (2005)

Are the RDAs Enough?

Vitamin D - used to say 400 to 800 IU per day. Now minimum 2,000 to 10,000/day. Magnesium - RDA was increased in 1907 from 350 to 420 mg. Vitamin C - RDA was increased in 2004 to 75 mg and 90 mg. up from 60 mg. previously for adults Vit E was incr from 8 or 10 mg. to 15 mg. for adults

Key Nutrients
Magnesium -bl glu reg, ins fx, blocks stress response Chromium - crucial for gl transport Vit D - insulin and immune regulation Vit C - improves energy transport in fat cells, incrs glutathione aiding removal of toxins Selenium - antiox enzyme, needed for thyroid hormone conversion Anitoxidants - C, E, Sel, Carotenoids,etc wide array needed to control inflammation

Magnesium Intake
Gallup poll 2004 commissioned by Purdue Products (makers of Slo Mag ) 80% not getting RDA just from diet 35% getting RDA between diet and supplements

July 21, 2004 PRNewswire

Magnesium and Type 2 DM

50 controlled, 110 non-controlled type 2 diabetes patients 190 healthy volunteers Serum HDL-cholesterol value showed signicant graded increase with serum magnesium values regardless of glucose values.

Guerrero-Romero F, et al. J Diabetes Complications 2000 Sep-Oct;14(5):272-6. Nutr Res. 2008 Oct;28(10): 659-653

Signs and Symptoms of Magnesium Deciency

Blood sugar dysregulation Depression Migraines Kidney Stones Osteoporosis Low energy/fatigue

Signs and Symptoms of Magnesium Deciency

Muscle cramps and spasms, including vasospasm Constipation Arrhythmia and heart palpitations Anxiety, nervousness, and insomnia Increased BP

Magnesium Supplements
Generally recommended dosages are 250750mg daily. Choose absorbable citrate, glycinate, amino acid chelate or malate forms.

Chromium
Improves satiety Carbohydrate cravings Helps convert T4 to T3 Metabolism of carbs and fats

Docherty JP, et al. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract. 2005 Sep;11(5):302-14. Lau FC, et al. Nutrigenomic basis of benecial effects of chromium(III) on obesity and diabetes. Mol Cell Biochem. 2008 Oct;317(1-2):1-10. Epub 2008 Jul 18. Review.

Chromium
1950s- Discovered that chromium was required by animals to control blood sugar 1970s- In hospitals chromium was added to TPN alongside insulin therapy to lower blood sugar. Insulin therapy wasnt effective on its own 1997- Dr. Richard Anderson (USDA) published a landmark study demonstrating the efcacy and saftey of chromium picolinate supplementation in people with type 2 DM Still not widely utlized to help control DM

Dietary Chromium: An Overview the Chromium Info Bureau Revised 1996 Chromium in Health and Disease Summit Summary 2003

Chromium
Important in insulin regulation and blood sugar control One of the most critical nutritional factors in IR Each insulin receptor needs four molecules of chromium Chromium attaches to the IR and changes its conguration allowing the insulin in the bloodstream to bind with the receptor allowing glucose to enter the cell

Chromium Results
Role in lowering cholesterol- triglycerides Inverse relationship between chromium levels in toenails and risk of MI including fatal MIs Pregnant woman with gestational DM supplemented with chromium had signicantly lower insulin and glucose levels vs placebo In patients with atypical depression (carbohydrate cravings, weight gain) 70% of patients taking chromium picolinate experienced relief from symptoms

Guruprasad R, et al. Mutat Res. 2006 November 7; 610(1-2): 93100. Rajpathak S, et al. Diabetes Care September 2004 vol. 27 no. 9 2211-2216 Jovanovic L, Gutierrez M, Peterson C. Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exper Med 1999; 12: 917. Chromium Supplementation May Reduce Carbohydrate Cravings in Atypical Depression J Psychiatr Pract. 2005;11:302-314

Stresses to Chromium Status

Can increase chromium excretion in the urine: Exercise- chromium excretion higher with intense exercise (90% VO2 max) and higher in less active more sedentary control subjects Pregnancy/Lactation- a normal state of chromium wasting Infection and Physical trauma Chromium losses increase with age High sugar diets
Vincent J. The biochemistry of chromium. Journal of Nutrition. 2000;130:715-718. Lau FC, et al. Nutrigenomic basis of beneficial effects of chromium(III) on obesity and diabetes. Mol Cell Biochem. 2008 Oct;317(1-2):1-10. Epub 2008 Jul 18. Review. Anderson RA, et al. Exercise Effects on Chromium excretion of trained and untrained men consuming a constant diet. J Appl Physiol 64: 249-252, 1988;

Chromium and Biotin

348 overweight and obese subjects with poorly controlled type 2 DM, Supplemented with 600 mcg chromium picolinate + 2 mg biotin Supplements added to current medications. Supplement subjects had 6% drop in fasting blood sugar, HgbA1C decreased more in supplement group vs placebo Preliminary studies show biotin may enhance chromiums effectiveness

Albarracin CA, et al. Diabetes Metab Res Rev 2008; 24: 4151.

Zinc and Chromium

Co-factors in the insulin receptor complex Shortages lead to insulin resistance and fat storage

Biol Trace Elem Res. 1995Jan-Mar;47(1-3):385-91 Diabetes Care 2006 Aug 29(8): 1826-32

Zinc Deciency
Zinc is required for maintaining a healthy metabolism Plays a key role in the synthesis and action of insulin and a big role in insulin resistance Recommended dose 15-100mg daily zinc amino acid chelate
Isbir T, et al. Diabetes Res. 26:4145, 1994.

Chromium Supplementation
RDA is set at about 35 mcg for adults Most of the studies that showed efcacy for lowering blood sugar or lipids used doses between 1 and 2 mg (1000-2000 mcg) Start at 1000 mcg New form of chromium, chromium histidinate complex, has been reported to signicantly improve absorption capability over current chromium nutritional supplements

Anderson RA, et al. Biol Trace Elem Res. 2004 Dec;101(3):211-8. Martin J, et al. Diabetes Care. 2006;29(8):1826-1832.

The Safety and Efcacy of High-dose Chromium

Chromium supplementation does result in tissue retention, especially in the kidney, although no pathogenic effect has been demonstrated despite considerable study The 350-fold difference between the acceptable daily intake and the calculated reference dose for humans of 70 mg per day seems without precedent with respect to other nutritional minerals.

Altern Med Rev. 2002 Jun;7(3):218-35.

Exercise and Nutrients

Regular intense exercise that induces sweating Sweating - helps remove toxins Also lose nutrients i.e. chromium excretion in urine increases with exercise, magnesium and other trace minerals are excreted in sweat and urine; need to keep nutr density high in diet.

Dunford and Doyle, Nutr in Sports and Exercise, 2008 Thomson and Wadsworth. Lukaski, H. Magnesium, chromium and zinc nutriture in physical activity. AJCN, 72;2:585S-93S. Aug. 2000

Vitamin C
Men with the lowest amount of vitamin C have a 62% increased risk of cancer and a 57% increased risk of dying from any cause. Vitamin C status and mortality in US adults.

Loria CM, et al. Am J Clin Nutr 72:139-45, 2000.

Deciencies and Exercise

Vitamin C up-regulates carnitine synthesis and increases fat burning. Study found people with marginal Vitamin C deciency burned 25% less fat during exercise. Repletion of Vitamin C raised fat burning 4 fold.

Nutrition and Metabolism 2006, 3:35 doi:10.1186/1743-7075-3-35

Vitamin D
Low Vitamin D levels are linked to increased blood sugar and insulin resistance Women with low Vitamin D more prone to gain visceral fat.

Am J Clin Nutr. 2010 April 14 J Clin Endocrinol Metab 2009 Jan 94 (1):67-73. Epub 2008 Nov. 4

Vitamin D
Supplemental vitamin D reduces the risk of colon cancer by half compared to dietary vitamin D which reduces it 12%. Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men.

Kearney J, et al. Am J Epidemiol 143:907-17, 1996.

Delta-6-desaturase
Enzyme critical for the conversion of linoleic acid to gamma linolenic acid GLA needed for the production of PGE1 and PGE3 (anti-inammatory prostaglandins) Several nutrients required for Delta 6 desat enzyme activity

Essential Fats for Vegetarians

Vegetarian levels of EPA/DHA are those of nonvegetarians Inefcient conversion of ALA to EPA & DHA due to high n-6 diets, trans fats; protein deciency; too much sugar, too much alcohol; vit B, magnesium and zinc deciency Conversion enzymes may not function well in people with metabolic syndrome, diabetes

Nutritional Co-factors
Necessary for PGE-1 and PGE-3 synthesis Vitamin B3 Vitamin B6 C Zinc Magnesium

Drug-Induced Nutrient Depletions Inuence Metabolism

Female Hormones: FA, B6, B1, B2, B3, B12, C, Mg, Se, Zn, tyrosine,CoQ10, E Anticonvulsants: D, K, FA, Ca Anti-diabetic Drugs: CoQ10, B12 Anti-hypertensives: B6, CoQ10, Ca, Mg, K, Zn, Anti-inflammatory: Ca, K, Zn, Fe, B6, C, D, FA, Statins: CoQ10, Vitamin D Beta-blockers: CoQ10, melatonin Phenothiazines/TCAs: B2, CoQ10 Benzodiazepines: Melatonin Anti-ulcer medications: B12, FA, D, Ca, Fe, Zn, Mg, protein Antibiotics: B-vitamins, vitamin K

Studies
More than 1,000,000 studies have been conducted on the 69 most popular supplements

Multi Vitamins
Multi-vit/min usage was assessed in RDBPC study 215 men ages 30 to 55 for effects on mood, stress, physical and mental tasks. Multi vit contained B complex, vit C and minerals After 33 days on the Multi vit/min the men report sig. higher ratings on general mental health, reduced subj. stress, increased vigor and overall improved mood. Task performance was also improved and mental fatigue was reduced after performing intense metal processing tasks compared to placebo group which had not sig. changes.
Northumbria University (2010, May 14). Multivitamins can add sparkle for healthy young people.ScienceDaily. Retrieved May 20, 2010, from http://www.sciencedaily.com/releases/2010/05/100514075108.htm

Safety
CDC data 2003 - 106,000 deaths from adverse drug reactions (16,500 from NSAIDS) 2003 - 12 deaths from dietary supplements

Inammation, Insulin Resistance and Diet

What Are Our Desired Endpoints

Support health/Prevent Disease Control weight Control inammation Strong, balanced immune system (Neuro -endocrine-immune)

Anti-inammatory high antioxidant nutrient dense low glycemic load non-reactive (low allergen) pure, unprocessed

Inammation and Diet

Trans fatty acids (found in hydrogenated oils) are extremely proinammatory. Even small intakes are associated with increased health risks such as heart disease and cancer. Trans fats induce insulin resistance and increase belly fat. Of all fats, trans fats have the strongest association with weight gain

Mozaffarian D, Aro A, Willett WC. Health effects of trans-fatty acids: experimental and observational evidence. Eur J Clin Nutr. 2009 May;63 Suppl 2:S5-21. Review. Wallace SK, Mozaffarian D. Trans-fatty acids and nonlipid risk factors. Curr Atheroscler Rep. 2009 Nov;11(6):423-33. Review. Willett WC. Trans fatty acids and cardiovascular disease-epidemiological data. Atheroscler Suppl. 2006;7(2):5-8.

Inammation and Diet

Antioxidantrich diet can be one of the best defenses against inammation Focus on getting adequate Omega-6 fatty acids from sh, plant foods, walnuts and wild game Studies have shown that sh oil signicantly lowers C reactive protein, compared to omega 6 fats like safower oil.
Balk EM, Lichtenstein AH, Chung M, et al. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006;189(1):19-30. Madsen T, Skou HA, Hansen VE, et al. C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol. 2001;88(10):1139-42.

Diet, Obesity, and IR

High rened sugar/carbohydrate diet and low in quality protein promotes fat storage and muscle catabolism High protein diets that restrict carbohydrates lack essential nutrients and ber Serotonin-carbohydrates at mealtime satisfy carb cravings but exacerbate IR Weight gain leads to increase resistin, decrease adiponectin, and inammation

Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995 Nov;3 Suppl 4:477S-480S. Review.

Dietary Recommendations in IR
A modied low carb/higher protein diet Increase non-starchy vegetable intake - improves adiponectin levels Utilize high ber foods like beans to fulll carb cravings without high adverse glycemic effects Lean meats - sh, chicken, bison A low allergen diet may be helpful, i.e. low wheat and/or cows milk.
Cassidy A, et al. Plasma adiponectin concentrations are associated with body composition and plant-based dietary factors in female twins. J Nutr. 2009 Feb;139(2):353-8. Epub 2008 Dec 23.

Low Carb vs High Carb for Wt. Loss

Brehm et al compared women on 15/28/57 vs 54/18/328 8.5 kg. vs 3.9 with no changes in bone mineral content in either group Low carb group had same body water as low fat group. Low carb had spontaneous restr of caloric intake (this effect seen in other studies.)
The J of Clin Endocrin & Metab Vol. 88, No. 4 1617-1623

Comparison of 4 diets
LEARN diet, -2.6 kg Zone, - 1.6 kg. Ornish (vegetarian, low fat), -2.2 kg Atkins, - 4.7 kg

Gardner et al. JAMA. 297 (9): 969 - 985.

4 Diets (contd)
Ornish and LEARN favored LDL at 2 mo., differences leveled out and were not signif. at 6 and 12 mos Lowest carb was most effective for weight loss, lowering of trigs, increasing HDL and lowering BP
Authors conclusions - Atkins diet led to greatest wt loss and most benecial metabolic effects through 1 yr of follow up

Low Carb and Metabolic Syndrome

Low carb/high fat diet improved BP, increased HDL, lowered trig, reduced bl glu and insulin, and reduced weight. Low fat/High carb diet exacerbated Metabolic Syndrome Authors discussed the persistance of AHA/NHBL in recommending low fat diets as being in error for Met Syndrome
Volek J, Feinman R. Nutr and Metab 2005,2:31

Low Carb and Lipids

Low carb diets lowered trig, increased HDL and lowered apoB even in absence of wt. loss or presence of higher sat fat when compared to low fat diets
Krauss, et al. AJCN 2006;83:1025-1031

 Obese subjects placed on low carb, high fat diet. No kcal restriction. Sodium intake went from 2 g to 20 g Lost 5% of body wt in 6 wks, had signif reductions in fasting insulin and mean aterial pressure Auth conclusions - we need to stop paying so much attn to sodium and start paying attn to fasting insulin
Hays JH Mayo Clin Proc 2003:78;1331-1336

Low Carb and Hypertension

Low Carb Studies

Low Carb High Protein (HP)diets were compared to high fat (HF) and High Carb High Fiber (HC) diets in 96 overweight women. 16 weeks Participants were given general weight loss counseling during rst 8 weeks, contd diets on their own during second 8 weeks. Results - next slide
McAuley, et al. Diabetologia (2005) 48:8-16

High vs. Low Carb Results

HC Weight Waist Trig - 5 kg - 7 cm. - .32 mmoL
13% had incr. LDL

HF - 7 kg -10.5 cm -.56 mmoL

LDL signif lower, but 25% had 10% incr LDL

HP -7 kg -9.7 cm -.63 mmoL

-LDL signif lower, but 7% had incr LDL

Insulin

-4.2 mU/L

-5.9

-3.8

Authors concl. - HP diet best overall approach for risk of CVD and Type II Diab in insulin resistant people

More Low Carb Support

Considering the effectiveness of VLCDs in promoting fat loss and improving the metabolic syndrome, discounting or condemning their use is unjustified. We encourage a more unbiased, balanced appraisal of VLCDs.
Volek et al. J. Nutr. 135:1339-1342, June 2005

Comparison of GI and GL
120 young adults - comparing 2 low vs. 2 high GL (all diets were low fat, reduced kcal) All groups lost wt. and waist circum High carb groups - one had lower GI, this group nearly doubled fat loss compared to high carb, high GI GI and GL inuenced results even within a low kcal diet. Reducing GL increased rate of fat loss esp. in women
Arch Int Med, July 24, 2006

Low vs High GI
162 subjects RDB study 1 yr. comparing high carb/ high GI, high carb/low GI, and low carb/high MUFA In well controlled Type 2 Diabetics (bl. glu near normal) a low GI diet led to lower 2 hr postload glu and CRPs were lowest in the low GI diet (1.95), highest in high carb/high GI (2.75)
Am J Clin Nutr 2008;87;114-25

Low GI Foods and Stress Hormones

Subjects (teenage boys) were given equal kcal meals with either high, med. or low GI High GI meals led to incr kcal intake and higher serum insulin, lower plasma glucagon, and elevated serum plasma epinephrine
Ludwig, et al. High Glycemic Index Foods , Overeating and Obesity. Pediatrics 103:e26 (1999)

Low Glycemic Improves Nutrition Status

The kidneys possibly lose their ability to retain magnesium during periods of hyperglycemia (signicantly elevated blood glucose). The increased loss of magnesium in urine may then result in lower blood levels of magnesium [4]. In older adults, correcting magnesium depletion may improve insulin response and action [42]. http://ods.od.nih.gov/factsheets/magnesium.asp

Low Carb and REE

2 calorie restricted diets, either low fat or GL Bl glu, trig, CRP and BP all improved more in low GL group REEs reduced less in the low GL group Low GL group also had less hunger
Pereira, MA, et al. JAMA. 292 (20):2482-2490

Safety of High Pro and Fat Evaluated

Carb Restricted Diets high in MUFA or Pro are equally effective at promoting fat loss and improving blood lipids (Luscombe-Marsh, et al. AJCN Apr. 2005 81:773-779) When substituted for carb, protein enhances fat loss. This study looked to see if the effect was from HP or higher MUFA. Both higher fat and protein diets led to fat loss, lower glucose and insulin responses and NO calcium loss, bone loss or renal changes.

Evaluation of Ketosis
Ketogenic (KLC) vs Non ketogenic (NLC) diets - 6 wks. Both were effective in weight 6.3 vs 7.2 kg and fat loss 3.4 vs 5.5 kg. REE and insulin sensitivity incr in both. Beta hydroxybutyrate was 3.6 x higher in KLC and was directly LDL correlated. LDL incr in 5, decr in 4 KLC. Incr in 2/Decr in 8 NLC KLC had incr. Arachidonic acid:eicosapentaenoic acid ratios in plasma phospholipids Vigor, happiness, energy rated much higher in NLC

Johnston et al. AJCN May 2006 83 (5):1055-61

High Protein Diet and Hip Fx in Elderly

Five hundred seventy-six women and 370 men from the Framingham Osteoporosis Study-no previous hx of hip fx 946 participants-mean age 75 yrs. Mean pro intake of 68g/d Increased protein intake associated with decreased risk of hip fracture compared to participants with lowest protein intake

Misra D, et al. Does dietary protein reduce hip fracture risk in elders? The Framingham osteoporosis study. Osteoporos Int. 2010 May 5. [Epub ahead of print]

High Protein Low Carb Diet + Exercise

48 women, 40 to 56 yrs. Randomly assigned to low carb:protein diet (PRO) or high carb:protein diet (CH0) + light walking (control) or exercise (EX) PRO and PRO + EX lost more total weight and fat mass and lost less lean mass than CHO and CHO & EX. CHO groups-greater reduction in chol and LDL chol. PRO groups-greater reduction in TRIG and greater inc. in HDL Exercise resulted in body fat loss and lean mass preservation Diet + exercise synergistic for improving body composition

Layman, D et al. Dietary Protein and Exercise Have Additive Effects on Body Composition during Weight Loss in Adult Women. J of Nutr. Downloaded from jn.nutrition.org on June 7, 2010

Net Acid Comparisons

Paleolithic era- meat was the only acid producing food. Net acid producing load (NEAP) was -78 to -23 mEq/d Modern NEAP is 48 to 132 mEq/d The primary dietary change in ancient vs. modern diet was replacement of roots, tubers, leafy greens, vegetables with grains and energy dense nutrient poor foods (separated fats and sugars)

Net Acid Load (contd)

Authors of the study stated that by replacing grains and NDEP foods with vegetables/plants would allow animal food intake to increase considerably without becoming a net-acid producing diet And proposed metabolic alkalinizing diet should be considered for preventing/treating osteoporosis, age-related muscle wasting, hypertension, kidney stones, infertility, age and disease related renal insufficiency, and even improved exercise performance.
Sebastian et al. AJCN 76 (6): 1308-16.

Fructose
Signif contributor to increased appetite, incr triglycerides, and incr risk insulin resistance and heart disease Major dietary sources- high fructose corn syrup, fruit juices, fruit Authors of this review urgently called for the reduction of high fructose additives in food supply Reason that even intake of fruit and esp fruit juice needs to be controlled
Nutrition & Metabolism 2005, 2:5 doi:10.1186/1743-7075-2-5

Metabolic Code Diet: Components of Diet Portion

Low carb, high fat and protein High emphasis on low-starch plant foods (vegetables, leafy greens) Fruits, beans/legumes eaten to tolerance Starches - grains, starchy vegs (corn, peas, potatoes) - usually no more than 1 -2 servings/day Low allergen diet - wheat and casein free Low rened, processed foods - a whole foods diet (no trans fat, rened sugar) Considers food purity - encourages organic foods to avoid pesticide residues, GM foods, antibiotics, growth hormones

Diet for Gut HealthElimination Diet

Same diet used for weight and lipid control (Low carb, high antiox, healthy pro and fat diet) Low sugar - sugar promotes proliferation of yeast Fermented foods are source of beneficial flora High fiber - fructo oligosaccharides promote growth of beneficial flora and SCFA production If symptomatic may need elimination diet: Wheat and dairy-most allergenic foods Processed foods-likely to contain traces of wheat and dairy Nitrite and nitrate-containing foods Sugar and all forms of sucrose-containing foods including maple syrup, honey, molasses, brown sugar, etc.

Metabolic Code Rationale for Supplements

Nutrients in foods declining Low kcal = reduced intake of micronutrients Replete inadequacies as evidenced by symptoms Support metabolic needs Safe and effective history of use

Supplement Safety and Regulation

Supplements regulated under DSHEA (Dietary Supplement Health an dEducation Acto, 1994) Supplement companies require to provide evidence their products are safe and effective for intended purpose. FDA has full authority to remove unsafe products Recently updated standards for supplement GMPs.

Regulation of Dietary Supplements

GMPs

National Nutritional Foods Association (NNFA), the herb and supplement industry's largest trade association, has run a program since 2002 FDA CGMP guidelines of 2008 Will require proper controls for dietary supplements - processed in a consistent manner, and meet quality standards Companies must already be in compliance (2010 deadline)

FDA vs. FTC

FDA (Food and Drug Administration)
Oversees manufacturing and labeling compliance

FTC (Federal Trade Commission)

Regulates advertising and marketing

Studies
More than 1,000,000 studies have been conducted on the 69 most popular supplements

Safety
CDC data 2003 - 106,000 deaths from adverse drug reactions (16,500 from NSAIDS) 2003 - 12 deaths from dietary supplements

Samples of Science
Daily supplements of calcium plus vitamin D, but not of vitamin D alone, are associated with significantly reduced fracture risk
Daily Calcium Plus Vitamin D Supplements May Reduce Fracture Risk BMJ. 2010;340:b5463.

Vitamin-D deficiency may account for several thousand premature deaths from cancers annually Garland CF,
Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health 2006; DOI: 10.2105/AJPH.2004.045260.

Choose Trusted Vendors

Douglas Laboratories: In-house laboratories, under the supervision of staff Ph.D.s, In house ISO-17025 accredited laboratories have the ability to test for:
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