1. Research Question In obese individuals who lose more weight on a low- carbohydrate diet versus a conventional diet, what are the underlying mechanisms?

2. Possible Mechanisms Metabolic Advantage 1. Ketogenesis, which involves the diet-induced production and excretion of fat- derived molecules called ketones. 2. Thermogenesis, which involves an increase in energy expenditure associated with the thermic effect of food (TEF). 3. Increased satiety, which involves the diet-induced reduction of hunger and calorie intake. The underlying mechanism might be psychological, physiological, or both. Metabolic Disadvantage 4. Water loss, due to the breakdown and use of glycogen. 5. Muscle wasting, due to protein degradation associated with gluconeogenesis.

3. Ketogenesis -When dietary carbohydrate intake decreases, insulin levels decrease. In response, free fatty acids (FFA) are released from adipose tissue into the bloodstream. FFAs are mobilized (transported) to the muscles and liver. -In muscle, FFAs can be used for ATP production. In addition, the muscles can use proteins and glycogen as energy sources. -In the liver, FFAs are converted into ketone bodies, which are transported in the blood to the brain, where they can be used for ATP production. The liver can also break down its glycogen stores to form glucose, which is transported to the brain. -When the body's carbohydrate stores fall to extremely low levels, glucose can be produced through gluconeogenesis. - What is the "metabolic advantage" theory of weight and fat loss? Readings: McDonald, 1996

4. Diet-induced Thermogenesis The thermic effect of food (TEF) is the increase in energy expenditure that occurs as a result of eating. In other words, it's the energy cost of chewing, digesting, absorbing, and storing food energy in the body. TEF is commonly calculated as a percentage of calories ingested. MacronutrientThermic Effect Fat~4% to 15% Carbohydrate~5 to 15% Protein~20 to 35% Readings: Halton and Hu (2004), Eisenstein et al. (2002), Johnston et al. (2002), Luscombe et al. (2003)

5. Evidence for the Thermogenic Hypothesis: Johnston et al. (2002) Objective: To measure the thermic effect of a high-protein meal Subjects: 10 healthy, normal-weight women Design: Randomized, cross-over Meals 1. High-CHO: 50% complex carbohydrate, 10% simple sugar, 15% protein and 25% fat 2. High-protein: 30% complex carbohydrate, 10% simple sugar, 30% protein and 30% fat Procedure For 2.5 hours following a breakfast, lunch, and dinner meal, resting energy expenditure (REE) was measured and compared to baseline values, in order to calculate TEF.

6. Johnston et al.’s Results The thermic effect was significantly greater for the high- protein meal versus the high-carbohydrate meal at breakfast and dinner.

7. Evidence against the Thermogenic Hypothesis: Luscombe et al. (2002) Objective: To measure thermic effect of a high-protein meal in subjects on a high-protein diet Subjects: 36 obese hyperinsulinemic men (n = 10) and women (n = 26) Design and Procedure Baseline (week 0): TEF measured in subjects after eating a low-protein meal or a high-protein meal Baseline (week 0): Subjects assigned either to a low-protein or high-protein diet Week 0 to week 12: Energy intake of the diets was restricted by ~30% relative to energy expenditure Week 12 to week 16: Energy intake was balanced. Week 16: TEF measured in subjects after eating a low-protein meal or a high-protein meal ER = energy restricted; EB = energy balanced

8. Luscombe et al.’s Results Low-Protein MealHigh-Protein Meal REE (kj/day) Week 077827890 Week 1670027240 Change-780-650 TEF (% energy intake) Week 07.19.1 Week 167.88.6 Change.69-.56 Key Findings 1. Although REE was significantly lower at week 16 than week 0 for subjects on both diets, there was no significant difference in the amount of change; thus, there was no effect of diet composition. 2. At week 0, the TEF after a high-protein (HP) test meal (9.1%) was significantly greater than that for a low- protein (LP) test meal (7.1%), although the difference was small. 3. At week 16, there was no statistically significant difference between the TEF values. 4. Over the 16-week period, the change in TEF was not statistically significant for either the LP or HP group.

9. Westerterp-Platenga (1999) : Evidence for Satiating Effects of Protein Objective: To determine whether (a) the satiating effects of the macronutrients differ and (2) satiety and diet-induced thermogenesis (DIT) are correlated Subjects: 8 normal-weight women Meals 1. High-protein: 29% P, 61% C, 10% F 2. High-fat: 9% P, 30% C, 61% F Design and Procedure Subjects consumed breakfast, lunch, and dinner meals in a respiratory chamber, enabling the researchers to measure DIT. At regular intervals before and after each meal, subjects rated feelings of satiety and hunger on a 100-mm visual analogue scale.

10. Westerterp-Platenga et al.’s Results Also, the difference in DIT between the diets was significantly correlated with the differences in satiety (r = 0.8, p <0.01)

11. deGraaf et al. (1992): Evidence against Satiating Effects of Protein Objective: To determine whether the satiating effects of the 3 macronutrients differ Subjects: 29 normal-weight women Meals: 10 550 mL-liquid breakfasts -- The control meal contained only 8 kcals -- The remaining 9 meals varied by macronutrient composition and energy level, as follows: Design and Procedure On different days, each subject consumed all 10 preload meals. Subjects then recorded their voluntary food intake for the rest of the day.

12. deGraaf et al.’s Results

13. Arguments against the Metabolic Advantage of Low- carbohydrate Diets 1. Low-carb diets cause excessive water loss Theory: One gram of carbohydrate is stored in the body with 3-4 grams of water. So when carbohydrate stores are lowered and not replenished through the diet, water is lost from the body. Supporting research: Yang & Van Itallie, 1976Yang & Van Itallie, 1976 Opposing research: Rabast et al., 1981Rabast et al., 1981 2. Low-carb diets cause excessive muscle loss Theory: When carbohydrate stores are lowered and not replenished through the diet, the body produces glucose through gluconeogenesis. A substrate for gluconeogenesis is protein, which can be taken (wasted) from muscle tissue.gluconeogenesis Supporting research: Rabast et al., 1981Rabast et al., 1981 Opposing research: Volek et al., 2002Volek et al., 2002