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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK072428 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Brigham and Women's Hospital | OTHER |
The aim of this study is to evaluate the effects of three dominant dietary patterns - conventional low-fat, low-glycemic index (GI) and very-low-carbohydrate - on energy metabolism and heart disease risk factors following weight loss in obese young adults in a feeding study
For most of the last half century, reduction in fat intake has been the primary nutritional approach for the prevention and treatment of obesity and cardiovascular disease (CVD). Over the last few years, very low carbohydrate (Atkins-type) diets have achieved great popularity, with publication of several studies suggesting greater weight loss and improvements in CVD risk factors over 3 to 6 months. Recently, a third dietary approach focused on glycemic index (GI) has generated interest. However, few studies have compared the effects of these diets on body weight regulation and risk for CVD. The primary hypotheses of this study are that any diet that lowers the postprandial rise in blood glucose (very-low-carbohydrate or low-GI) will have beneficial effects on the physiological adaptations to weight loss and on some CVD risk factors. However, other CVD risk factors will be adversely affected by a very-low-carbohydrate vs. a low-GI diet. Preliminary data provide strong support for these hypotheses, by showing that resting energy expenditure declines less and CVD risk factors improve more with weight loss on a low-glycemic load diet compared to a conventional low-fat diet. This application proposes a cross-over feeding design to study the effects of three diets following 12.5% weight loss in obese young adult subjects (n = 24, age 18 to 40 years). The diets are: 1) conventional low-fat, with 60% carb, 20% fat, 20% protein; 2) low-GI with 40% carb, 40% fat, 20% protein; and 3) very-low-carbohydrate with 10% carb, 60% fat, 30% protein. The primary outcome is resting energy expenditure (indirect calorimetry). Secondary outcomes include total energy expenditure (doubly labeled water), thermic effect of food (indirect calorimetry), physical activity (accelerometry), insulin resistance and B-cell function (frequently-sampled OGTT), blood lipids, blood pressure and measures of systemic inflammation and coagulopathy. This study should have major public health implications to the millions of Americans currently following diets to decrease body weight and risk for heart disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Low glycemic index diet |
|
| 2 | Active Comparator | Low fat diet |
|
| 3 | Active Comparator | Very low carbohydrate diet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low glycemic index diet | Other | Feeding protocol, all foods prepared in a metabolic kitchen |
| |
| Measure | Description | Time Frame |
|---|---|---|
| resting energy expenditure using indirect calorimetry in the fasting state | end of each dietary period | |
| insulin resistance assessed by frequently-sampled oral glucose tolerance test | end of each dietary period | |
| thyroid function tests | end of each dietary period |
| Measure | Description | Time Frame |
|---|---|---|
| total energy expenditure using doubly labeled water methodology | end of each dietary period | |
| thermic effect of food using indirect calorimetry | end of each dietary period | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David S Ludwig, MD, PhD | Boston Children's Hospital | Principal Investigator |
| Cara B Ebbeling, PhD | Boston Children's Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23483989 | Result | Walsh CO, Ebbeling CB, Swain JF, Markowitz RL, Feldman HA, Ludwig DS. Effects of diet composition on postprandial energy availability during weight loss maintenance. PLoS One. 2013;8(3):e58172. doi: 10.1371/journal.pone.0058172. Epub 2013 Mar 6. | |
| 22735432 | Result | Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA. 2012 Jun 27;307(24):2627-34. doi: 10.1001/jama.2012.6607. |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D018752 | Diet, Fat-Restricted |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 |
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| Low fat diet |
| Other |
Feeding protocol, all foods prepared in a metabolic kitchen |
|
| Very low carbohydrate diet | Other | Feeding protocol, all foods prepared in a metabolic kitchen |
|
| physical activity using accelerometry |
| end of each dietary period |
| serum lipids | end of each dietary period |
| plasminogen activator inhibitor-1 | end of each dietary period |
| C-reactive protein | end of each dietary period |
| blood pressure | end of each dietary period |
| hunger/appetite | end of each dietary period |
| insulin 30 minutes after oral glucose (as an effect modifier) | baseline |
| Core temperature | End of each dietary period |
| secreted frizzle-related protein-4 | end of each dietary period |
| heme-oxygenase | end of each dietary period |
| Irisin | end of each dietary period |
| fibroblast growth factor-21 | end of each dietary period |
| chemerin | end of each dietary period |
| trimethylamine N-oxide | fasting and postprandial, end of each dietary period |
| alanine aminotransferase | end of each dietary period |
| Uric acid | end of each dietary period |
| insulin | fasting and postprandial, end of each dietary period |
| ghrelin | fasting and postprandial, end of each dietary period |
| gastric inhibitory peptide | fasting and postprandial, end of each dietary period |
| GLP1 | fasting and postprandial, end of each dietary period |
| PYY | fasting and postprandial, end of each dietary period |
| Amylin | fasting and postprandial, end of each dietary period |
| Leptin | end of each dietary period |
| Metabolomic analysis | Evaluate the effect of diet on metabolomic profile in plasma, with the aim of assessing dietary adherence and exploring diet-disease mechanisms | end of each dietary period |
| 41547934 | Derived | Angelidi AM, Bartell E, Huang Y, Zeleznik OA, Estanyol-Torres N, Mi MY, Bhupathiraju SN, Kelly RS, Wittenbecher C, Lasky-Su J, Clish CB, Ludwig DS, Ebbeling CB, Hirschhorn JN. Weight-independent effects of dietary carbohydrate-to-fat ratio on metabolomic profiles: secondary outcomes of a 5-month randomized controlled feeding trial. Nat Commun. 2026 Jan 17;17(1):1662. doi: 10.1038/s41467-026-68353-z. |
| 28694840 | Derived | Hron BM, Ebbeling CB, Feldman HA, Ludwig DS. Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary macronutrient composition and relationship with metabolism. Nutr Metab (Lond). 2017 Jul 5;14:44. doi: 10.1186/s12986-017-0198-y. eCollection 2017. |
| 28077380 | Derived | Esko T, Hirschhorn JN, Feldman HA, Hsu YH, Deik AA, Clish CB, Ebbeling CB, Ludwig DS. Metabolomic profiles as reliable biomarkers of dietary composition. Am J Clin Nutr. 2017 Mar;105(3):547-554. doi: 10.3945/ajcn.116.144428. Epub 2017 Jan 11. |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |