DEBATE: Weight as a Measure of Health vs. Health at Every Size - PowerPoint PPT Presentation

DEBATE: Weight as a Measure of Health vs. Health at Every Size Concepts Christopher Gardner, PhD Professor of Medicine Nutrition Scientist Stanford Prevention Research Center Stanford University, Department of Medicine

No Conflicts of Interest to Disclose

Abby King John Ioannidis Tom Robinson Jennifer Robinson Antonella Dewell Josephine Hau Alana Koehler Mandy Murphy Rise Cherin Susan Kirkpatrick Dalia Perlman Jae Berman Manisha Desai Julie Parsonnet Robert Haile Sarah Farzinkhou Valerie Alaimo Mollie Shimer Diane Demis Tracey McLaughlin Kari Nadeau Justin Sonnenberg Kenji Nagao, PhD Erin Avery Katherine Dotter Ben Chrisinger, PhD Katarina Balter, PhD Michelle Hauser Lucia Aronica John Trepanowski Liana Del Gobbo Lisa Offringa Jennifer Hartle MD PhD PhD PhD PhD PhD Cindy Shih, MS

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Outline Ø My research & lessons learned Ø Evidence for Obesity links to Morbidity/Mortality Ø Health at Every Weight Ø Take Home / Actionable Conclusions

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults The Evidence Report. National Institutes of Health. Obes Res 1998;6(Suppl)2:51S-209S. Carb ~15% Fat Protein >55% <30% ≥ 55% energy from carbohydrate ≤ 30% energy from fat and approximately 15% energy from protein

Low carb High carb

Gardner, JAMA 2007;297:969-77 A Weight Loss Diet Study

From Low-Carb to Low-Fat 100 Protein 80 60 % Energy 40 Fat 20 0 Carbohydrate Gardner, JAMA 2007;297:969-77

8 weeks 6 months 1 year A TO Z Study Diet Data 17% 22% 23% 28% 32% 30% NDS Atkins 3-day 46% 47% 55% unannounced 24-hr recalls (3,137 recalls) Zone Carb Data not presented Fat Protein LEARN 16% 18% 19% Ornish 52% 53% 21% 63% 29% 29% Gardner, JAMA 2007;297:969-77

Percent weight change across time, by group 0 Gardner, JAMA 2007;297:969-77 -1 -2 Weight Zone -3 Ornish change A vs. Z LEARN -4 p<0.03 as % of (Tukey ’ s -5 studentized -6 baseline range test) Atkins -7 -8 -9 6 months 1 year Base- 8 line weeks % Retention 1-year Participants with available data Atkins 77 72 71 68 88% Zone 79 72 66 61 77% LEARN 79 72 64 60 76% Ornish 76 71 65 58 78%

1 year Favored Group assigned to Atkins 22% 32% Low-Carbohydrate WEIGHT p=0.03 46% HDL-C p=0.0004 SBP p=0.001 DBP p=0.004 (not adjusted for multiple testing) Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults Carb The Evidence Report. National Institutes of Health. Obes Res 1998;6(Suppl)2:51S-209S. Fat ~15% Protein >55% <30% 19% 52% National Guidelines 29% Gardner, JAMA 2007;297:969-77

12-month net weight change (kg): Individual results 20 15 10 5 0 -5 -10 -15 -20 -25 -30 20 15 10 5 0 -5 -10 -15 -20 -25 -30 20 15 10 5 0 -5 -10 -15 -20 -25 -30 20 15 10 5 0 -5 -10 -15 -20 -25 Gardner, JAMA 2007;297:969-77 -30

12-month net weight change (kg): Individual results 20 15 10 5 0 -5 -10 -15 -20 ~30 kg RANGE of -25 -30 20 15 10 weight change 5 0 -5 -10 -15 WITHIN each diet -20 -25 -30 20 15 group. 10 5 0 -5 -10 -15 -20 -25 -30 From losing 20-25 kg 20 15 10 5 to gaining 5-10 kg 0 -5 -10 -15 -20 -25 Gardner, JAMA 2007;297:969-77 -30

Percentage Change in Weight Yancy et al., Arch Int Med, 2010;170:143 -30 -0 Percentage Change in Weight -30 -0

Dansinger et al., Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk Reduction: A Randomized Trial. JAMA, 2005; 293:43-53

Percent weight change across time, by group 0 -1 -2 Weight -3 Ornish change -4 as % of -5 -6 baseline Atkins -7 -8 -9 6 months 1 year Base- 8 % Retention line weeks 1-year Participants with available data Atkins 77 72 71 68 88% Ornish 76 71 65 58 78%

Fasting A TO Z Study: Exploratory analyses Insulin Tertiles Ornish Diet (very low fat, high carb) Atkins (very low carb, unrestricted fat and protein) 0 Most -2 n=19 Weight loss (kg) Insulin -4 Sensitive -6 (<7 µ IU/mL) n=24 -8 -10 0 Most -2 Insulin n=23 -4 Resistant (>10 µ IU/mL) -6 n=21 -8 0 2 6 12 -10 Months Mean, SEM

Fasting A TO Z Study: Exploratory analyses Insulin Tertiles Ornish Diet (very low fat, high carb) Atkins (very low carb, unrestricted fat and protein) 0 Most -2 Success with either n=19 Weight loss (kg) Insulin -4 diet for those who are Sensitive -6 (<7 µ IU/mL) relatively insulin n=24 -8 sensitive -10 0 Most For those who are -2 Insulin n=23 insulin resistant, -4 Resistant low-fat diet (>10 µ IU/mL) -6 n=21 ineffective compared -8 0 2 6 12 to low-carb diet -10 Months Mean, SEM

Weight Loss by Adherence Tertile (A TO Z Study) p=0.0006 p=0.01 p=0.06 2 0 Adherence tertiles n= n= n= 19 19 23 -2 12-Month Highest Weight Lowest -4 Change n= (kg) 19 n= -6 19 n= -8 23 -10 Atkins Zone Ornish Alhassan, Intl J Obesity , 2008; 57:49-56

McClain et al., Diabetes Obes Metab 2013;15:87-90 Change in % Carbs Change in % Fats +25% +20% +20% +10% +15% 0 +10% +5% -10% 0 -5% -20% -10% -30% -15% -20% -40% 0 2 6 0 2 6 12 12 Months Months Assigned to Assigned to Fasting Insulin Atkins Ornish Tertiles (Lowest Carb) (Lowest Fat) Lowest (most Ins Sens) Highest (most Ins Res)

Differential Adherence by Insulin Resistance Status Insulin resistant individuals may find it inherently more difficult to adhere to a lower-fat/higher-carb diet

Ongoing Study: NIH R01 DK091831 + NuSI Ø Study Population: Women & men, BMI 28-40, age 18-50, non-diabetic, general good health Ø Sample size: n=609 (enrollment complete) Ø Intervention: Healthy Low-Fat vs. Healthy Low-Carb Weight loss diets Delivered in 22 instructional sessions (~17/class) Ø Primary outcome : 12-month weight loss Ø Possible mediators/moderators: Genome, metabolome, microbiome Insomnia, food addiction, psychosocial, many others

How Low can you go? ~20 grams/day (carbs or fat)? Titr itrat ate up t e up to a o a le level y el you can ou can maintain….. maint ain….. FOREVER OREVER

Healthy Low-Fat vs. Healthy Low-Carb Healthy Low-Fat vs. Healthy Low-Carb

ID 14: Low Fat BREAKFAST 2 slices whole wheat bread w/mustard Multigrain cereal w/skim milk Water LUNCH 4 c salad mix w/ fat-free dressing Spinach spaghetti w/ marinara sauce Mid-afternoon snack Coffee DINNER Stir fried veggies w/ kung pao sauce, soy sauce and garlic on brown rice Water Evening Snack Pita bread w/ low-fat red pepper hummus

ID 36: Low Fat BREAKFAST Low Fat Latte Scone LUNCH Vegetable lasagna Soda Mid-afternoon snack Water Martini w/ olives DINNER Minestrone soup Linguini w/ shrimp, alfredo & marinara sauce Caesar Salad Evening Snack Red wine Chocolate cake

ID 36 ID 14 Low Fat

Low Fat ID 36 ID 14 1,950 1,700 Kcal 36% 13% Fat 37% 73% Carbohydrate 17% 14% Protein 10% 0% Alcohol 15 g 45 g Fiber 1 g 1 g Omega-3 36 g 4 g Saturated fat 39 g 20 g Added Sugars

ID 10: Low Carb BREAKFAST Tuna salad w/ tomatoes, olives & lettuce Fat free dressing Water LUNCH Deli ham Laughing cow cheese Afternoon Snack Coffee w/ half and half DINNER Chicken w/o skin Zucchini & Broccoli sauteéd in butter Evening Snack Strawberries & sparkling water

ID 51: Low Carb BREAKFAST Omelette w/ cheese, ham, spinach Coffee with half & half Water LUNCH Steak w/ cheese Pork ribs Bratwurst Broccoli salad Water DINNER Cheeseburger Sausage Avocado, tomato, spinach Red wine

ID 10 ID 51 Low Carb

Low Carb ID 51 ID 10 2,150 Kcal 1,200 66% Fat 48% 5% Carbohydrate 13% 23% Protein 39% 6% Alcohol 0% 8 g Fiber 13 g 2 g Omega-3 2 g 61 g Saturated fat 21 g 4 g Added Sugars 5 g

Do Genotype Patterns Predict Weight Loss Success for Low Carb vs. Low Fat Diets? R01 DK091831 (2013-17) + NuSI n=609 Low Carbohydrate (n=305) . BMI 28-40 kg/m 2 non-diabetic generally healthy adults 18-50 yrs Low Fat (n=304) ~55% women Months 0 3 6 12 INTERVENTION : XXXXXXXX X X X X X X X X X X X X X X 22 group classes, 15-22 participants/group WEIGHT (1° outcome) X X X X Blood (DNA, lipids, glucose, X (no OGTT) X X X insulin, OGTT, cytokines) Diet Assessment (NDS-R) X X X X Psychosocial (Questionnaires) X X X X DEXA, REE (Metabolic cart) X X X Other: Microbiome (fecal samples) Adipocytes (fat biopsies), Other – Various times points, specific cohorts

Non-Diabetic, Insulin Resistant 150 40 140 30 >125 mg/dL cut off for 130 25 diabetes 120 Blood 20 Serum 75 grams Glucose Insulin glucose (mg/dL) uU/mL 110 15 100 10 90 5 0 0 0 30 60 120 Minutes