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Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial
Open accessAbstract
Objective: To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure. Design: Randomized trial. Setting: Multicenter collaboration at US two sites, August 2014 to May 2017. Participants: 164 adults aged 18-65 years with a body mass index of 25 or more. Interventions: After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose). Main outcome measures: The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin. Results: Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (−6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol). Conclusions: Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion. Trial registration: ClinicalTrials.gov NCT02068885 .
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“Furthermore, studies suggest a unique diet–phenotype interaction, in that individuals with high insulin secretion or other abnormalities of glucose homeostasis appear especially susceptible to adverse metabolic responses and weight gain when consuming a high-GL diet (96, 105–110).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [106]
In the citing paper
“data from a large 5-mo study demonstrating increased energy expenditure when consuming a low-carbohydrate diet during weight-loss maintenance appear robust (106, 153, 154).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [106]
In the citing paper
“More recent studies have indicated that weight loss is often similar to comparison diets in the long term, but low-carbohydrate diets may have advantages in reducing diabetic medication and reducing triglycerides, while increasing HDL cholesterol [51–53, 54••, 55, 56••].”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [51]
In the citing paper
“Total EE was greatest in the lowest-carbohydrate group, and there was a linear trend of 52 kcal/d per 10% reduction in dietary carbohydrates.”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [51]
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Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates
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Research works printed but not linked: 1
- Holsen L, Cerit H, Lennerz B, et al. Hypothalamic and nucleus accumbens cerebral blood flow vary as a function of long-term carbohydrate-to-fat ratio diets [abstract]. Neuropsychopharmacology (American College of Neuropsychopharmacology 56th Annual Meeting, Palm Springs) 2017;42:S150-1. https://www.nature.com/articles/npp2017264.pdf
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Kirkpatrick, C. F., Bolick, J. P., Kris-Etherton, P. M., Sikand, G., Aspry, K. E., Soffer, D. E., Willard, K.-E., & Maki, K. C. (2019) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2019.08.003 · Cited by 390
The carbohydrate-insulin model: A physiological perspective on the obesity pandemic
Ludwig, D. S., Aronne, L. J., Astrup, A., de Cabo, R., Cantley, L. C., Friedman, M. I., Heymsfield, S. B., Johnson, J. D., King, J. C., Krauss, R. M., et al. (2021) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab270 · Cited by 292
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Metadata
- Authors
- Ebbeling, C. B., Feldman, H. A., Klein, G. L., Wong, J. M. W., Bielak, L., Steltz, S. K., Luoto, P. K., Wolfe, R. R., Wong, W. W., & Ludwig, D. S.
- Affiliations
- Boston Children's Hospital (US)
- Framingham State University (US)
- University of Arkansas for Medical Sciences (US)
- Baylor College of Medicine (US)
- Corresponding author
- Ludwig, David S
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2018-11-14
- Volume
- 363
- Pages
- k4583
- ISSN
- 1756-1833 (ISSN-L)
- 0959-8138
- PMC
- PMC6233655
- OpenAlex
- W2900786730
- Cited by
- 274
- References
- 91
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 24 · 2023: 41 · 2022: 36 · 2021: 43 · 2020: 47 · 2019: 40 · 2018: 3
- FWCI
- 22.80
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-11-03)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMJ (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Framingham State University Digital Repository (Framingham State University) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Brigham and Women's Hospital
- Ohio State University
- Laura and John Arnold Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK082730)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- low-carbohydrate diet, energy expenditure, weight loss maintenance, carbohydrate-to-fat ratio, insulin secretion, resting energy expenditure, physical activity, leptin, ghrelin, obesity, dietary protein, energy balance, appetite-regulating hormones, weight regain prevention
- MeSH terms
- Adolescent, Adult, Aged, Energy Metabolism, Female, Humans, Insulin, Male, Middle Aged, Weight Loss, Body Mass Index, Treatment Outcome, Overweight, Carbohydrate Metabolism, Diet, Carbohydrate-Restricted, Young Adult
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