Marlene Most

Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating: A Randomized Controlled Trial

CONTEXT The role of diet composition in response to overeating and energy dissipation in humans is unclear. OBJECTIVE To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition. DESIGN, SETTING, AND PARTICIPANTS A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. INTERVENTION After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884-1022 kcal/d). MAIN OUTCOME MEASURES Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8. RESULTS Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88-4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84-7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23-7.79 kg) (P = .002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102-218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165-289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11-3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37-3.98 kg]) increased significantly with the normal and high protein diets. CONCLUSIONS Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00565149.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study

BACKGROUND Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. OBJECTIVE We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. DESIGN In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. RESULTS Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P < 0.01) increased total fecal cholesterol excretion (36 +/- 6% and 74 +/- 10%, respectively) and biliary cholesterol excretion (38 +/- 7% and 77 +/- 12%, respectively) and reduced percentage intestinal cholesterol absorption (-10 +/- 1% and -25 +/- 3%, respectively). Serum LDL cholesterol declined significantly only with the highest phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). CONCLUSIONS Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

Increased Food Intake and Energy Expenditure Following Administration of Olanzapine to Healthy Men

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ‐induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double‐blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12‐day washout. Twenty‐four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18–49 years) and 22.6 ± 2.2 kg/m2, respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor‐I (PAI‐I), leptin, and tumor necrosis factor‐α (TNF‐α) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short‐term perturbations in IS.

The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial

Background/Objectives:Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism.Subjects/Methods:In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers.Results:The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), P<0.0001) and 79% higher fecal cholesterol excretion (1322±112 (1083.2, 1483.3) vs 739±97 mg/day (530.1, 930.2), P<0.0001) relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), P<0.0001). LDL-cholesterol was similar between diets.Conclusions:Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

Effects of Dairy Products on Intracellular Calcium and Blood Pressure in Adults with Essential Hypertension

Background: Consumption of dairy foods has been associated with lower blood pressure in certain populations. Objective: This study examined the effects of dairy foods on blood pressure (BP) and intracellular calcium ((Ca)i) and the dependence of BP changes on changes in (Ca)i. Design: Twenty-three stage 1 hypertensive adults were fed the following 3 experimental diets (5 wk each) in a randomized cross-over design study; a dairy-rich, high fruits and vegetables diet (D-F&V; 30% fat, 7% saturated fat (SFA), 3.4 servings/d dairy), a high fruits and vegetables diet (F&V; 30% fat, 7% SFA, 0.4 servings/d dairy), and an average Western diet (control; 36% fat, 15% SFA, 0.4 servings/d dairy). Systolic (SBP) and diastolic (DBP) BP, calcium regulatory hormones, and erythrocyte (Ca)i were determined. Results: SBP and DBP were significantly reduced by ∼2 mm Hg following both D-F&V and F&V diets vs. the control (P < 0.05). The D-F&V diet significantly lowered 1,25-dihydroxyvitaminD compared with the F&V and control diets (P < 0.01). Serum calcium, parathyroid hormone, calcitonin, and renin activity were unchanged. The D-F&V diet lowered (Ca)i vs. the other two diets (P < 0.01), and this change correlated with the fall in DBP (r = 0.52, P < 0.05). Subjects who responded to the D-F&V diet by significantly reducing (Ca)i exhibited significantly greater net decreases in DBP on the D-F&V vs. the F&V (−2.8 ± 1.0 mm Hg) and control diets (−5.4 ±1.0 mm Hg; diet × group interaction, P < 0.02). Conclusion: Consumption of dairy foods beneficially affects (Ca)i, resulting in improved BP in a subgroup defined by (Ca)i response.

Reducing the Glycemic Index or Carbohydrate Content of Mixed Meals Reduces Postprandial Glycemia and Insulinemia Over the Entire Day but Does Not Affect Satiety

OBJECTIVE We evaluated the effects of mixed meals differing in glycemic index (GI) and carbohydrate content on postprandial serum glucose and insulin response, hunger, and satiety over the course of a 12-h day. RESEARCH DESIGN AND METHODS In this randomized crossover trial, 26 overweight or obese adults received four diets in random order (high GI, high carbohydrate [HGI-HC]; high GI, low carbohydrate [HGI-LC]; low GI, high carbohydrate [LGI-HC]; and low GI, low carbohydrate [LGI-LC]). All meals were prepared by a metabolic kitchen. Participants received breakfast, lunch, and dinner over the course of a 12-h day. Primary outcomes were postprandial serum glucose and insulin quantified as area under the curve. Hunger, fullness, and satiety were assessed by visual analog scale. RESULTS The HGI-LC, LGI-HC, and LGI-LC diets significantly reduced glucose and insulin area under the curve compared with the HGI-HC diet (P < 0.001 for all comparisons). There were no significant differences in ratings of hunger, fullness, or satiety between the different dietary treatments. CONCLUSIONS Reducing the GI or carbohydrate content of mixed meals reduces postprandial glycemia and insulinemia, and these changes can be sustained over the course of an entire day. However, there were no differences in subjective hunger and satiety ratings between the diets. These results demonstrate that maintaining a low GI or glycemic load diet is an effective method of controlling serum glucose and insulin levels.

Effect of a 3-day high-fat feeding period on carbohydrate balance and ad libitum energy intake in humans.

Objective:A reduction in glycogen after the switch to an isoenergetic high-fat diet (HFD) might promote a compensatory increase in food intake to reestablish carbohydrate balance. We assessed the effect of an isoenergetic switch from a 49%-carbohydrate to 50%-fat diet on nutrient balance and ad libitum food intake. We hypothesized that carbohydrate balance would be inversely related to ad libitum energy intake.Methods:In 47 men and 11 women (22.6±0.4 years; 26.1±0.5 kg m–2), fuel balance was measured in a respiration chamber over 4 days. During the first day, an isoenergetic, high-carbohydrate diet was provided followed by a 3-day isoenergetic, HFD. At the end of this period and after 16 h of fasting, three options of foods (cookies, fruit salad and turkey sandwich) were offered ad libitum for 4 h. The relationships between post-chamber ad libitum intake and macronutrient oxidation and balance measured day-to-day and over the 4-day respiration chamber stay were studied.Results:After switching to a HFD, 24-h respiratory quotient decreased from 0.87±0.02 to 0.83±0.02 (P<0.0001) resulting in a 4-day cumulative carbohydrate, fat and protein balances of −183±368, 342±480 and 65±267 kcal, respectively. Cumulative energy balance (224±362 kcal per 4 days) did not influence ad libitum energy intake. However, we detected that 4-day carbohydrate balance was a positive and independent predictor of post-chamber ad libitum energy intake (R 2=0.10; P=0.01), whereas no significant influence of fat and protein balances was found.Conclusion:In response to an isoenergetic change from a high-carbohydrate to HFD, higher carbohydrate balance related to increased energy intake.

Hormonal Responses to a Fast-Food Meal Compared with Nutritionally Comparable Meals of Different Composition

Background: Fast food is consumed in large quantities each day. Whether there are differences in the acute metabolic response to these meals as compared to ‘healthy’ meals with similar composition is unknown. Design: Three-way crossover. Methods: Six overweight men were given a standard breakfast at 8:00 a.m. on each of 3 occasions, followed by 1 of 3 lunches at noon. The 3 lunches included: (1) a fast-food meal consisting of a burger, French fries and root beer sweetened with high fructose corn syrup; (2) an organic beef meal prepared with organic foods and a root beer containing sucrose, and (3) a turkey meal consisting of a turkey sandwich and granola made with organic foods and an organic orange juice. Glucose, insulin, free fatty acids, ghrelin, leptin, triglycerides, LDL-cholesterol and HDL-cholesterol were measured at 30-min intervals over 6 h. Salivary cortisol was measured after lunch. Results: Total fat, protein and energy content were similar in the 3 meals, but the fatty acid content differed. The fast-food meal had more myristic (C14:0), palmitic (C16:0), stearic (C18:0) and trans fatty acids (C18:1) than the other 2 meals. The pattern of nutrient and hormonal response was similar for a given subject to each of the 3 meals. The only statistically significant acute difference observed was a decrease in the AUC of LDL cholesterol after the organic beef meal relative to that for the other two meals. Other metabolic responses were not different. Conclusion: LDL-cholesterol decreased more with the organic beef meal which had lesser amounts of saturated and trans fatty acids than in the fast-food beef meal.

The effects of triiodothyronine on bone metabolism in healthy ambulatory men.

The purpose of the present study was to determine the effects of supraphysiologic doses of triiodothyronine (T(3)) on skeletal metabolism, calcium balance, and the calciotropic hormones. Seven healthy, lean men were studied in an inpatient metabolic unit over a 63-day period. All volunteers received oral T(3) at doses of 50-75 microg/d. There was a prompt and sustained increase in calciuria and an overall net negative calcium balance. The pattern of changes in serum osteocalcin, urinary deoxypyridinoline (DPD)/creatinine ratio, and serum bone-specific alkaline phosphatase indicated an early increase in bone resorption followed by a late, incomplete compensatory increase in bone formation. Cumulative net calcium loss was 18.5 +/- 5.4 g over the 63-day treatment period, averaging 218.5 +/- 41.4 mg/d. This represents 0.22% +/- 0.075% of the total skeletal calcium content. The cumulative net calcium loss over the 63-day treatment period was highly correlated with the change in DPD (r = -0.95, p = 0.001). Prompt increases in corrected serum calcium values resulted in serum intact parathyroid hormone (iPTH) levels decreasing by 30.4% (p = 0.08). Bone mineral density showed no change. We conclude that T(3) accelerates bone turnover and that bone formation does not increase acutely to prevent bone loss.

Triiodothyronine increases calcium loss in a bed rest antigravity model for space flight

Bed rest has been used as a model to simulate the effects of space flight on bone metabolism. Thyroid hormones accelerate bone metabolism. Thus, supraphysiologic doses of this hormone might be used as a model to accelerate bone metabolism during bed rest and potentially simulate space flight. The objective of the study was to quantitate the changes in bone turnover after low doses of triiodothyronine (T(3)) added to short-term bed rest. Nine men and 5 women were restricted to bed rest for 28 days with their heads positioned 6 degrees below their feet. Subjects were randomly assigned to receive either placebo or oral T(3) at doses of 50 to 75 microg/d in a single-blind fashion. Calcium balance was measured over 5-day periods; and T(3), thyroxine, thyroid-stimulating hormone, immunoreactive parathyroid hormone, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline were measured weekly. Triiodothyronine increased 2-fold in the men and 5-fold in the women during treatment, suppressing both thyroxine and thyroid-stimulating hormone. Calcium balance was negative by 300 to 400 mg/d in the T(3)-treated volunteers, primarily because of the increased fecal loss that was not present in the placebo group. Urinary deoxypyridinoline to creatinine ratio, a marker of bone resorption, increased 60% in the placebo group during bed rest, but more than doubled in the T(3)-treated subjects (P < .01), suggesting that bone resorption was enhanced by treatment with T(3). Changes in serum osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, were similar in T(3)- and placebo-treated subjects. Triiodothyronine increases bone resorption and fecal calcium loss in subjects at bed rest.