Conventional Model of Obesity Effects of Dietary Glycemic Load on - PDF document

Conventional Model of Obesity Effects of Dietary Glycemic Load on Energy Expenditure: Results from the Framingham State Food Study Cara B. Ebbeling, PhD March 29, 2019 2019 Massachusetts Academy of Nutrition and Dietetics Annual Nutrition Convention & Exposition Ludwig, Ebbeling. JAMA Intern Med 2018;178:1098-103. Disclosure Carbohydrate-Insulin Model of Obesity Cara B. Ebbeling, PhD, MS Effects of Dietary Glycemic Load on Energy Expenditure: Results from the Framingham State Food Study FINANCIAL DISCLOSURE No relevant financial relationship exists Ludwig, Ebbeling. JAMA Intern Med 2018;178:1098-103. Background Meta-Analysis • Biological factors strongly influence body weight of Short-Term Studies  With weight loss, hunger increases and energy expenditure decreases Hall, Guo. Gastroenterology 2017;152:1718-27  Physiological adaptations defend against long term weight change • Genetic factors are known to affect body weight  Explain some of the variance in BMI  Cannot explain why the average person today, compared with 40 years ago, seems to be “defending” a much higher body weight Maclean et al. Am J Physiol Regul Integr Comp Physiol 2011;301:R581-600 Leibel et al. N Engl J Med 1995;332:621-8

Published Manuscripts ♦ (FS)2 ♦ 2018 • Ludwig DS, Ebbeling CB. The Carbohydrate-Insulin Model of Obesity: Beyond "Calories In, Calories Out". JAMA Intern Med 2018;178:1098-103. • “The only consistent finding among the trials is that adherence • Ebbeling CB, Klein GL, Luoto PK, Wong JMW, Bielak L, Eddy RG, Steltz SK, Devlin C, … was most strongly associated with weight loss and Sandman M, Hron B, Shimy K, Heymsfield SB, Wolfe RR, Wong WW, Feldman HA, Ludwig DS. A randomized study of dietary composition during weight-loss maintenance: rationale, improvement in disease-related outcomes.” study design, intervention, and assessment. Contemp Clin Trials 2018;65:76-86. • “The pursuit of the ideal macronutrient content diet is • Wong JM, Bielak L, Eddy RG, Stone L, Lakin PR, Sandman M, Devlin C, Seger-Shippee L, unidimensional, ignoring 2 of the 3 major components of Wiroll D, Luoto PK, Klein GL, Ludwig DS, Ebbeling CB. An academia-industry partnership for standard lifestyle interventions: behavioral modification and planning and executing a community-based feeding study. Curr Dev Nutr 2018;2:nzy060. exercise. To consider lifestyle interventions as diets ignores • Ebbeling CB, Feldman HA, Klein GL, Wong JMW, Bielak L, Steltz SK, Luoto PK, Wolfe RR, their complexity, with behavioral modification as the piece that Wong WW, Ludwig DS. Effects of a low carbohydrate diet on energy expenditure during specifically addresses adherence.” weight loss maintenance: randomized trial. BMJ 2018;363:k4583. JAMA  August 21, 2013 • To evaluate dietary composition in the context of lifestyle interventions ignores the Diverse Audience importance of conducting trials with high internal validity before aiming to test external validity. Practitioners – Public Health Professionals – Researchers Faculty – Staff – Students – Media Study Participants – Patients– People Interested in Healthful Nutrition Inside the Study Internal Validity Balance Is the study designed to answer the question at hand? • Technical scientific “language” Is there only one independent variable • “Lay terms” (i.e., dietary composition)? Outside the Study Linkages External Validity • Data collection protocols Are findings applicable in other circumstances? • Reported data Reported Data • Feeding studies provide the best approach for maximizing internal validity when • Numbers • Bottom line evaluating the effects of diets varying in macronutrient composition. Partnerships Framingham State Food Study: (FS)2 Specific Aim Research team To evaluate the effect of three diets varying widely in carbohydrate-to-fat ratio (high- carbohydrate, moderate-carbohydrate, low-carbohydrate) on energy expenditure during weight-loss maintenance, using a controlled feeding protocol. Food service team Lay Terms Energy Expenditure  Calories Burned – “Burn Rate” Hypothesis Total energy expenditure during weight-loss maintenance will differ among test diets through 20 weeks. Primary Outcome Assabet Valley Regional Technical High School TEE, assessed by doubly-labeled water methodology ClinicalTrials.gov Identifier: NCT02068885

Practically speaking, what was Weight Loss and Weight-Loss Maintenance the research question? Participant AV-4198-4 Withings Wi-Fi Scale 81 79 77 PRE Anchor 76.9 kg Body Weight (kg) 75 This suggests that calorie content of a diet is more important than composition. 12.2% weight loss 73 “A calorie is a calorie!” 71 + 2 kg 69 START Anchor 67.5 kg Does it really matter whether calories come 67 from carbohydrate or fat?  2 kg 65 9/14/2016 5/10/2017 Methods Macronutrient Composition of Test Diets Study Design and Dietary Interventions What proportion of calories came from carbohydrate vs. fat? Primary Outcome HI Carb MOD Carb LO Carb • Total Energy Expenditure Targets Consistency and Differentiation Carbohydrate (% energy) Secondary Outcomes 60 40 20 Added Sugar (% total carbohydrate) 15 15 15 • Resting Energy Expenditure Fat (% energy) 20 40 60 • Physical Activity and Sedentary Time Saturated Fat (% total fat) 35 35 35 • Skeletal Muscle Work Efficiency Protein (% energy) 20 20 20 • Fasting Blood Draw: 1,5-Anhydroglucitol, Ghrelin Effect Modifier • Insulin Secretion (FS)2 Study Design Dinner Example Run-In Diet Run-In Phase Test Phase Consistency and Differentiation 60% Calorie Needs 45% Carbohydrate Weight Loss Weight-Loss Maintenance Prepared Meals 30% Fat 25% Protein 12  2% Weight HI Carb MOD Carb LO Carb Stabilization Herb Grilled Salmon, 55 g Herb Grilled Salmon, 90 g Herb Grilled Salmon, 80 g High-Carbohydrate Diet – HI Carb Leaf Spinach, 100 g Leaf Spinach, 100 g Leaf Spinach, 100 g Long Grain & Wild Rice, 115 g Long Grain & Wild Rice, 100 g -- Run-in Diet Moderate-Carbohydrate Diet – MOD Carb -- Cheddar Cheese, 10 g Cheddar Cheese, 15 g Greek Yogurt, non-fat, 160g -- -- Dried cranberries, 20 g -- -- Low-Carbohydrate Diet – LO Carb Whole Wheat Bread, 27 g Whole Wheat Bread, 22 g -- -- Peanuts, 8 g Peanuts, 33 g Orange Sections, 180 g Orange Sections, 165 g Orange Sections, 95 g Assessment Period Randomization Milk, skim, 80 g Milk, 2%, 120 g Milk, 3.25%, 180 g (stable body weight) -- -- Salt, 0.3 g PRE START MID END -16 -12 -8 -4 0 4 8 12 16 20 WEEKS

(FS)2 Kitchen Intervention Integrity How well did we implement the intervention? • Food service staff completed: 95% of the intended spot weight checks 97% of the intended packaged menu item checks • For completed spot weight checks, comparing actual weights with target weights: 67% of the menu items within narrow tolerance limits ±0.1 g of target for items ≤ 10 g and ±0.5 g for items > 10 g 98% were within ±5 g deviation that would not compromise macronutrient differentiation • For the packaged menu item checks: 99% of the take-out meals contained all intended menu items Methods Study Design and Dietary Interventions Primary Outcome • Total Energy Expenditure Secondary Outcomes • Resting Energy Expenditure • Physical Activity and Sedentary Time • Skeletal Muscle Work Efficiency • Fasting Blood Draw: 1,5-Anhydroglucitol, Ghrelin Effect Modifier • Insulin Secretion Research Center “The (FS)2 House” >160,000 meals!

Total Energy Expenditure Disappearance Curves of 2 H and 18 O Data from Spot Urine Samples Protocol Doubly-Labeled Water Participant: AV-4198-4 (START) Methodology Dose of 2 H 2 18 O Spot urine sample Metabolic Period 0 1 14 Difference in rates of disappearance days Carbon dioxide production  Total Energy Expenditure Methods Isotope Enrichment Study Design and Dietary Interventions Back to Basic Chemistry! Primary Outcome Element Mass % Natural Doubly-Labeled • Total Energy Expenditure Number Abundance Water Secondary Outcomes 1 99.985 • Resting Energy Expenditure H 2 0.015 2 H 2 18 O • Physical Activity and Sedentary Time 16 99.76 • Skeletal Muscle Work Efficiency O 18 0.204 • Fasting Blood Draw: 1,5-Anhydroglucitol, Ghrelin protons + neutrons in an atom Mass number: Effect Modifier chemically identical, different number of neutrons (different mass) Isotopes: • Insulin Secretion Secondary Outcomes Isotopic Label Elimination How do the isotopes leave the body? • Resting Energy Expenditure Calories burned at rest • Carbonic anhydrase reaction H + + HCO 3 CO 2 + H 2 O H 2 CO 3 - Equilibrium between oxygen atoms in exhaled carbon dioxide and body water provides a biochemical basis for doubly-labeled water methodology. • Label elimination 18 O C 18 O 2 and H 2 18 O 2 H 2 18 O • Physical Activity and Sedentary Time 2 H 2 H 2 O