Friday, September 5

1. Friday, September 5 • Discuss the science background for our topic • IPHY 3700 Writing Process Map

2. Our Research Questions • Do low-carbohydrate diets offer a metabolic advantage for weight loss? • Do low-carbohydrate diets cause significant changes in markers of cardiovascular health?

3. Low-carbohydrate diets and weight loss: Conflicting study findings Golay et al. (1996):No significant difference in weight loss between subjects on a 1,000 kcal/day high-carbohydrate diet (45% of total calorie intake) versus subjects on an isocaloric low-carbohydrate diet (15% of total calorie intake) Samaha et al. (2003):Subjects on a low-carbohydrate (Atkins) diet lost significantly more weight than subjects on a conventional high-carbohydrate diet

4. Low-carbohydrate diets: Effects on weight and blood lipids

5. Shortcomings of Previous Studies 1. In all of the longer studies (6 months and beyond), subjects lived in their communities and attempted to follow instructions for their assigned diets. The subjects self-reported their food intake. 2. Some of the studies included nutrition education and exercise programs, which can be considered extraneous variables. 3. In studies on low-carbohydrate diets and cardiovascular health, researchers have not controlled for the confounding effects of weight loss. 4. Researchers have not designed their studies to definitively determine the mechanisms by which low-carbohydrate diets cause weight loss and changes in blood lipids. For example, the question of whether the diets afford a “metabolic advantage” (substantial weight loss despite energy balance or positive energy dynamics) has not been answered conclusively. 5. No study to date has exceeded 1 year.

6. If low-carbohydrate diets do indeed cause greater weight loss, the underlying mechanisms might involve . . . 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. 4. Water loss, due to the breakdown and use of glycogen. 5. Muscle wasting, due to protein degradation associated with gluconeogenesis.

7. 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?

8. 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. Readings: Halton and Hu (2004), Eisenstein et al. (2002), Johnston et al. (2002), Luscombe et al. (2003)

9. 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.

10. 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.

11. Evidence against the Thermogenic Hypothesis: Luscombe et al. (2002) Objective: To determine the effects of energy restriction and a high-protein diet on body weight, resting energy expenditure (REE), and TEF Subjects: 36 obese hyperinsulinemic men (n = 10) and women (n = 26) Design and Procedure • Baseline (week 0): Subjects were randomly assigned either to a low-protein or high-protein diet; REE and TEF were measured in subjects after eating a low-protein meal or a high-protein meal • Week 0 to week 12: Energy intake of the two diets was restricted by ~30% relative to energy expenditure • Week 12 to week 16: Energy intake of the two diets was balanced (with energy expenditure). • Week 16: Body weight, REE, and TEF were measured in subjects after eating a low-protein meal or a high-protein meal ER = energy restricted; EB = energy balanced

12. Luscombe et al.’s Results for Body Weight

13. Luscombe et al.’s Results for REE and TEE Key Findings 1. REE was significantly lower at week 16 than at week 0 for subjects on both diets; thus, the 12-week period of calorie restriction and weight loss significantly slowed resting metabolism. However, there was no significant difference in the amount of change across the two groups; thus, there was no effect of diet composition on REE. 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; thus, there was no effect of diet composition on TEF.

14. Latner & Schwartz (1999) : Evidence for Satiating Effects of Protein Objective: To determine the effects of dietary protein on satiety and food intake Subjects: 12 normal-weight women Meals 1. High-protein lunch (450 kcals): 71.5% P, 9.5% C, 19.2% F 2. High-carbohydrate lunch (450 kcals): 0% P, 99% C, 0% F 3. Combined lunch (450 kcals): 35.7% P, 55.1% C, 9.6% F Design and Procedure On three separate occasions, subjects consumed one of the three lunch meals in liquid form. Between 4.5 to 4.75 hours later, subjects consumed a buffet-style dinner meal. Outcome measures included the caloric value of each subject’s dinner and the subject’s responses to a questionnaire designed to assess feelings of hunger and satiety.

15. Latner & Schwartz’s (1999) Results

16. A Metabolic Disadvantage of Low-carbohydrate Diets? 1. Do low-carbohydrate 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, 1976 Opposing research: Rabast et al., 1981 2. Do low-carbohydrate 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. Supporting research: Rabast et al., 1981 Opposing research: Volek et al., 2002

17. Mechanisms Relating Insulin Resistance and Dyslipidemia: Part 1 Liver Insulin-resistant fat cells release large amounts of free fatty acids into the circulation. These FFAs are taken up by the liver, which uses them to form triglycerides. Fat Cells FFA X IR Slide source: Lipids Online Slide Library (http://www.lipidsonline.org)

18. Mechanisms Relating Insulin Resistance and Dyslipidemia: Part 2 Increased levels of triglycerides lead to the production of apolipoprotein (apo) B and very low density lipoprotein (VLDL). The release of VLDL into the blood contributes to the development of LDL-cholesterol. Fat Cells Liver FFA TG Apo B VLDL VLDL X IR Insulin Slide source: Lipids Online Slide Library (http://www.lipidsonline.org)

19. Atherosclerosis 1. A once-normal arterial wall (coronary artery) can be damaged through various mechanisms. 2. Formation of a fatty streak: LDL-C builds up under the endothelial lining. LDL-C is oxidized by free radicals. In response, cells of the immune system (macrophages) are mobilized to the area. 3. Formation of stable plaques: The plaque can be pushed into the lumen by thickening of smooth muscle cells. 4. Vulnerable plaques: Stable plaques can disintegrate and rupture, forming thrombi, or blood clots, which can block blood flow through the coronary arteries.