Effects of high vs low glycemic index of dietary carbohydrate on cardiovascular disease risk factors and insulin sensitivity: the OmniCarb randomized clinical trial.

IMPORTANCE: Foods that have similar carbohydrate content can differ in the amount they raise blood glucose. The effects of this property, called the glycemic index, on risk factors for cardiovascular disease and diabetes are not well understood. OBJECTIVE: To determine the effect of glycemic index and amount of total dietary carbohydrate on risk factors for cardiovascular disease and diabetes. DESIGN, SETTING, AND PARTICIPANTS: Randomized crossover-controlled feeding trial conducted in research units in academic medical centers, in which 163 overweight adults (systolic blood pressure, 120-159 mm Hg) were given 4 complete diets that contained all of their meals, snacks, and calorie-containing beverages, each for 5 weeks, and completed at least 2 study diets. The first participant was enrolled April 1, 2008; the last participant finished December 22, 2010. For any pair of the 4 diets, there were 135 to 150 participants contributing at least 1 primary outcome measure. INTERVENTIONS: (1) A high-glycemic index (65% on the glucose scale), high-carbohydrate diet (58% energy); (2) a low-glycemic index (40%), high-carbohydrate diet; (3) a high-glycemic index, low-carbohydrate diet (40% energy); and (4) a low-glycemic index, low-carbohydrate diet. Each diet was based on a healthful DASH-type diet. MAIN OUTCOMES AND MEASURES: The 5 primary outcomes were insulin sensitivity, determined from the areas under the curves of glucose and insulin levels during an oral glucose tolerance test; levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides; and systolic blood pressure. RESULTS: At high dietary carbohydrate content, the low- compared with high-glycemic index level decreased insulin sensitivity from 8.9 to 7.1 units (-20%, P = .002); increased LDL cholesterol from 139 to 147 mg/dL (6%, P ≤ .001); and did not affect levels of HDL cholesterol, triglycerides, or blood pressure. At low carbohydrate content, the low- compared with high-glycemic index level did not affect the outcomes except for decreasing triglycerides from 91 to 86 mg/dL (-5%, P = .02). In the primary diet contrast, the low-glycemic index, low-carbohydrate diet, compared with the high-glycemic index, high-carbohydrate diet, did not affect insulin sensitivity, systolic blood pressure, LDL cholesterol, or HDL cholesterol but did lower triglycerides from 111 to 86 mg/dL (-23%, P ≤ .001). CONCLUSIONS AND RELEVANCE: In this 5-week controlled feeding study, diets with low glycemic index of dietary carbohydrate, compared with high glycemic index of dietary carbohydrate, did not result in improvements in insulin sensitivity, lipid levels, or systolic blood pressure. In the context of an overall DASH-type diet, using glycemic index to select specific foods may not improve cardiovascular risk factors or insulin resistance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00608049.

Effects of diet composition on postprandial energy availability during weight loss maintenance.

BACKGROUND: The major circulating metabolic fuels regulate hunger, and each is affected by dietary composition. An integrated measure of postprandial energy availability from circulating metabolic fuels may help inform dietary recommendations for weight maintenance after weight loss. AIM: We examined the effect of low-fat (LF, 60% of energy from carbohydrate, 20% fat, 20% protein), low-glycemic index (LGI, 40%-40%-20%), and very low-carbohydrate (VLC, 10%-60%-30%) diets on total postprandial metabolic fuel energy availability (EA) during weight loss maintenance. METHODS: Eight obese young adults were fed a standard hypocaloric diet to produce 10-15% weight loss. They were then provided isocaloric LF, LGI, and VLC diets in a randomized crossover design, each for a 4-week period of weight loss maintenance. At the end of each dietary period, a test meal representing the respective diet was provided, and blood samples were obtained every 30 minutes for 5 hours. The primary outcome was EA, defined as the combined energy density (circulating level × relative energy content) of glucose, free fatty acids, and ß-hydroxybutyrate. Secondary outcomes were individual metabolic fuels, metabolic rate, insulin, glucagon, cortisol, epinephrine, and hunger ratings. Respiratory quotient was a process measure. Data were analyzed by repeated-measures analysis of variance, with outcomes compared in the early (30 to 150 min) and late (180 to 300 min) postprandial periods. RESULTS: EA did not differ between the test meals during the early postprandial period (p = 0.99). However, EA in the late postprandial period was significantly lower after the LF test meal than the LGI (p<0.0001) and VLC (p<0.0001) test meals. Metabolic rate also differed in the late postprandial period (p = 0.0074), with higher values on the VLC than LF (p = 0.0064) and LGI (p = 0.0066) diets. CONCLUSION: These findings suggest that an LF diet may adversely affect postprandial EA and risk for weight regain during weight loss maintenance.

Effects of dietary composition on energy expenditure during weight-loss maintenance.

CONTEXT: Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied. OBJECTIVE: To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss. DESIGN, SETTING, AND PARTICIPANTS: A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings. INTERVENTION: After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks. MAIN OUTCOME MEASURES: Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components. RESULTS: Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged. CONCLUSION: Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00315354.

Acute effects of dietary glycemic index on antioxidant capacity in a nutrient-controlled feeding study.

Oxidative stress, caused by an imbalance between antioxidant capacity and reactive oxygen species, may be an early event in a metabolic cascade elicited by a high glycemic index (GI) diet, ultimately increasing the risk for cardiovascular disease and diabetes. We conducted a feeding study to evaluate the acute effects of low-GI compared with high-GI diets on oxidative stress and cardiovascular disease risk factors. The crossover study comprised two 10-day in-patient admissions to a clinical research center. For the admissions, 12 overweight or obese (BMI: 27-45 kg/m(2)) male subjects aged 18-35 years consumed low-GI or high-GI diets controlled for potentially confounding nutrients. On day 7, after an overnight fast and then during a 5-h postprandial period, we assessed total antioxidant capacity (total and perchloric acid (PCA) protein-precipitated plasma oxygen radical absorbance capacity (ORAC) assay) and oxidative stress status (urinary F(2alpha)-isoprostanes (F(2)IP)). On day 10, we measured cardiovascular disease risk factors. Under fasting conditions, total antioxidant capacity was significantly higher during the low-GI vs. high-GI diet based on total ORAC (11,736 +/- 668 vs. 10,381 +/- 612 micromol Trolox equivalents/l, P = 0.002) and PCA-ORAC (1,276 +/- 96 vs. 1,210 +/- 96 micromol Trolox equivalents/l, P = 0.02). Area under the postprandial response curve also differed significantly between the two diets for total ORAC and PCA-ORAC. No diet effects were observed for the other variables. Enhancement in plasma total antioxidant capacity occurs within 1 week on a low-GI diet, before changes in other risk factors, raising the possibility that this phenomenon may mediate, at least in part, the previously reported effects of GI on health.

Alternatives for macronutrient intake and chronic disease: a comparison of the OmniHeart diets with popular diets and with dietary recommendations.

BACKGROUND: Enhancements to current dietary advice to prevent chronic disease are of great clinical and public health importance. The OmniHeart Trial compared 3 diets designed to reduce cardiovascular disease (CVD) risk-one high in carbohydrate and 2 that replaced carbohydrate with either unsaturated fat or protein. The lower carbohydrate diets improved the CVD risk factors. Several popular diets claiming health benefits emphasize carbohydrate, fat, or protein or various combined approaches. OBJECTIVE: The objective of this study was to compare the macronutrient contents of the OmniHeart trial diets to those of several popular diets and to evaluate each diet for consistency with national health guidelines. DESIGN: The macronutrient contents of 7-d menu plans from the OmniHeart Study, Dietary Approaches to Stop Hypertension (DASH), Zone, Atkins, Mediterranean, South Beach, and Ornish diets were evaluated for consistency with the US Food and Nutrition Board's Acceptable Macronutrient Distribution Ranges (AMDRs) and with the dietary recommendations of several health organizations. RESULTS: The OmniHeart diets fulfilled the major AMDRs, but, of the popular diets, only the Zone diet did. The OmniHeart diets were generally consistent with national guidelines to prevent cancer, diabetes, and heart disease, whereas most popular diets had limitations for fulfilling one or more guidelines. CONCLUSIONS: Although the OmniHeart protein and unsaturated fat diets were superior to the carbohydrate diet in improving CVD risk, all 3 study diets were consistent with national guidelines to reduce chronic disease risk, which suggests that the guidelines might now be fine-tuned to optimize disease prevention. Popular diets vary in their nutritional adequacy and consistency with guidelines for risk reduction.

Characteristics of the diet patterns tested in the optimal macronutrient intake trial to prevent heart disease (OmniHeart): options for a heart-healthy diet.

OBJECTIVE: To describe the nutrient and food composition of the diets tested in the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart). DESIGN: Two center, randomized, three-period crossover, controlled feeding trial that tested the effects of three healthful diet patterns on blood pressure, serum lipid levels, and estimated cardiovascular risk. SUBJECTS/SETTING: One hundred sixty-four participants with prehypertension and hypertension. During the 19 weeks of feeding, participants were required to consume only food prepared as part of the trial. INTERVENTION: The OmniHeart trial studied three diet patterns that differed in macronutrient composition: a carbohydrate-rich diet similar to the Dietary Approaches to Stop Hypertension diet (58% carbohydrate, 15% protein, and 27% fat), a higher protein diet that had 10% more protein and 10% less carbohydrate (48% carbohydrate, 25% protein, and 27% fat), and a higher unsaturated fat diet that had 10% more unsaturated fat and 10% less carbohydrate (48% carbohydrate, 15% protein, and 37% fat). Each diet contained 6% saturated fat and 100 to 200 mg cholesterol. Sodium was 2,300 mg at the 2,100 kcal energy level and was indexed across energy levels. Calcium, magnesium, and potassium were consistent with recommendations for the Dietary Approaches to Stop Hypertension diet and also indexed to energy levels. Each diet pattern met the major nutrient recommendations set by the Dietary Guidelines for Americans 2005. The 10% protein increase in the higher protein diet emphasized plant protein; however, meat and dairy food sources were also increased somewhat. Olive oil, canola oil, and olive oil spread were used liberally to achieve the unsaturated fat content of the higher unsaturated fat diet. The 10% reduction in carbohydrate in the higher protein diet and the higher unsaturated fat diet was achieved by replacing some fruits with vegetables, reducing sweets, and using smaller portions of grain products. All three diets reduced blood pressure, total and low-density lipoprotein cholesterol levels, and estimated coronary heart disease risk. CONCLUSIONS: The OmniHeart diet patterns offer substantial flexibility in macronutrient intake that should make it easier to eat a heart-healthy diet and reduce cardiovascular disease risk.

Acceptability of sodium-reduced research diets, including the Dietary Approaches To Stop Hypertension diet, among adults with prehypertension and stage 1 hypertension.

OBJECTIVE: Examine the acceptability of sodium-reduced research diets. DESIGN: Randomized crossover trial of three sodium levels for 30 days each among participants randomly assigned to one of two dietary patterns. PARTICIPANTS/SETTING: Three hundred fifty-four adults with prehypertension or stage 1 hypertension who were participants in the Dietary Approaches to Stop Hypertension (DASH-Sodium) outpatient feeding trial. INTERVENTION: Participants received their assigned diet (control or DASH, rich in fruits, vegetables, and low-fat dairy products), each at three levels of sodium (higher, intermediate, and lower) corresponding to 3,500, 2,300, and 1,200 mg/day (150, 100, and 50 mmol/day) per 2,100 kcal. MAIN OUTCOME MEASURES: Nine-item questionnaire on liking and willingness to continue the assigned diet and its level of saltiness using a nine-point scale, ranging from one to nine. STATISTICAL ANALYSES PERFORMED: Generalized estimating equations to test participant ratings as a function of sodium level and diet while adjusting for site, feeding cohort, carryover effects, and ratings during run-in. RESULTS: Overall, participants rated the saltiness of the intermediate level sodium as most acceptable (DASH group: 5.5 for intermediate vs 4.5 and 4.4 for higher and lower sodium; control group: 5.7 for intermediate vs 4.9 and 4.7 for higher and lower sodium) and rated liking and willing to continue the DASH diet more than the control diet by about one point (ratings range from 5.6 to 6.6 for DASH diet and 5.2 to 6.1 for control diet). Small race differences were observed in sodium and diet acceptability. CONCLUSIONS: Both the intermediate and lower sodium levels of each diet are at least as acceptable as the higher sodium level in persons with or at risk for hypertension.

Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.

CONTEXT: Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. OBJECTIVE: To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. DESIGN, SETTING, AND PARTICIPANTS: Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. INTERVENTIONS: A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. MAIN OUTCOME MEASURES: Systolic blood pressure and low-density lipoprotein cholesterol. RESULTS: Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P = .01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. CONCLUSION: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00051350.

Rationale and design of the Optimal Macro-Nutrient Intake Heart Trial to Prevent Heart Disease (OMNI-Heart).

BACKGROUND: The DASH (Dietary Approaches to Stop Hypertension) diet is a carbohydrate-rich, reduced-fat diet that lowers blood pressure (BP) and LDL-cholesterol. Whether partial replacement of some carbohydrate (C) with either protein (P) or unsaturated fat (U) can further improve these and other cardiovascular (CVD) risk factors is unknown. METHODS: OmniHeart is a randomized, three-period, crossover feeding study designed to compare the effects on BP and blood lipids of a carbohydrate-rich diet (CARB, similar to the DASH diet) with a diet rich in protein (PROT, predominantly from nonmeat sources) and a diet rich in unsaturated fat (UNSAT, predominantly monounsaturated). Throughout feeding (run in and the three intervention periods), participants are provided with all of their meals that meet the nutrient profile of their assigned diet. Calorie intake is adjusted to maintain weight. The target sample size is 160 (50% African-American). Participants are adults, aged 30 or older, with prehypertension or Stage 1 hypertension (systolic BP 120-159 or diastolic BP 80-99 mmHg). The primary outcome variables are systolic BP and LDL-cholesterol. Secondary outcomes are diastolic BP, HDL-cholesterol, and triglycerides. Other outcome variables are total cholesterol, apolipoproteins VLDL-apoB, VLDL-apoCIII, apolipoprotein B, non-HDL cholesterol, and lipoprotein(a), and insulin resistance, as measured by Homeostasis Model Assessment (HOMA). CONCLUSIONS: OMNI-Heart should advance our fundamental knowledge of the effects of diet on both traditional and emerging risk factors, and, in the process, guide policy makers, health care providers and the general public on the relative benefits of carbohydrate, protein, and unsaturated fat as a means to reduce CVD risk.

Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss.

CONTEXT: Weight loss elicits physiological adaptations relating to energy intake and expenditure that antagonize ongoing weight loss. OBJECTIVE: To test whether dietary composition affects the physiological adaptations to weight loss, as assessed by resting energy expenditure. DESIGN, STUDY, AND PARTICIPANTS: A randomized parallel-design study of 39 overweight or obese young adults aged 18 to 40 years who received an energy-restricted diet, either low-glycemic load or low-fat. Participants were studied in the General Clinical Research Centers of the Brigham and Women's Hospital and the Children's Hospital, Boston, Mass, before and after 10% weight loss. The study was conducted from January 4, 2001, to May 6, 2003. MAIN OUTCOME MEASURES: Resting energy expenditure measured in the fasting state by indirect calorimetry, body composition by dual-energy x-ray absorptiometry, cardiovascular disease risk factors, and self-reported hunger. RESULTS: Resting energy expenditure decreased less with the low-glycemic load diet than with the low-fat diet, expressed in absolute terms (mean [SE], 96 [24] vs 176 [27] kcal/d; P = .04) or as a proportion (5.9% [1.5%] vs 10.6% [1.7%]; P = .05). Participants receiving the low-glycemic load diet reported less hunger than those receiving the low-fat diet (P = .04). Insulin resistance (P = .01), serum triglycerides (P = .01), C-reactive protein (P = .03), and blood pressure (P = .07 for both systolic and diastolic) improved more with the low-glycemic load diet. Changes in body composition (fat and lean mass) in both groups were very similar (P = .85 and P = .45, respectively). CONCLUSIONS: Changes in dietary composition within prevailing norms can affect physiological adaptations that defend body weight. Reduction in glycemic load may aid in the prevention or treatment of obesity, cardiovascular disease, and diabetes mellitus.