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Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men
Open accessAbstract
Background The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat.Objective We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition.Design Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW).Results Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass.Conclusion The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.
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“With a KD, ketonemia is maximal within approximately 2 weeks [152].”
From International Society of Sports Nutrition position stand: diets for body weight reduction (2026) · cites this paper as [152]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By contrast, AT does not occur after glycogen depletion in response to an isocaloric ketogenic diet and moderate weight loss [78].”
From Changes in energy expenditure with weight gain and weight loss in humans (2016) · cites this paper as [78]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Compared with the baseline diet, the ketogenic diet was not accompanied by increased body fat loss but coincided with increased protein utilization and loss of fat-free mass [19].”
From Body Composition Changes in Weight Loss: Strategies and Supplementation for Maintaining Lean Body Mass, a Brief Review (2018) · cites this paper as [19]
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In the citing paper
“Fat oxidation increases via the KD reaches maximal levels and plateaus within the first week of the diet [152].”
From International Society of Sports Nutrition position stand: diets for body weight reduction (2026) · cites this paper as [152]
In the citing paper
“In comparisons conducted under matched energy intake, KD did not demonstrate superiority over higher carbohydrate diets in reducing body weight [48].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [48]
In the citing paper
“Differences in total body weight loss were, however, small [48].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [48]
In the citing paper
“In a short term, tightly controlled metabolic study comparing isocaloric diets, KD was associated with higher fat oxidation and lower insulin concentrations, whereas the high carbohydrate diet resulted in greater adipose tissue loss.”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [48]
In the citing paper
“KD characterized by a very low carbohydrate intake below 50 g/day and a high fat content typically providing 70 to 80% of total energy, results in the maintenance of state of ketosis [48].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [48]
In the citing paper
“However, metabolic studies conducted under conditions of balanced energy intake indicate that the KD is not superior to diets higher in carbohydrates in terms of fat loss [48].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [48]
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 [55]
In the citing paper
“The results indicated EE was 151 kcal/d higher for the very-low-carbohydrate diet as measured by the doubly labeled water (DLW) method.”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [55]
In the citing paper
“Results from two well-controlled metabolic ward studies also support this conclusion, in terms of the substitution of fat in place of carbohydrates resulting in higher EE [55, 56••].”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [55]
In the citing paper
“The more rapid total weight loss in the first few weeks observed from low-carbohydrate diets compared to low-fat diets likely involves loss of water weight and lean body mass, as evidenced from two well-controlled metabolic ward studies [55, 56].”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [55]
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Metadata
- Authors
- Hall, K. D., Chen, K. Y., Guo, J., Lam, Y. Y., Leibel, R. L., Mayer, L. E., Reitman, M. L., Rosenbaum, M., Smith, S. R., Walsh, B. T., & Ravussin, E.
- Affiliations
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Pennington Biomedical Research Center (US)
- Columbia University (US)
- Translational Research Institute for Metabolism and Diabetes (US)
- Corresponding author
- Hall, Kevin D
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 104
- Issue
- 2
- Pages
- 324-333
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC4962163
- OpenAlex
- W2469199053
- Cited by
- 330
- References
- 48
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 23 · 2023: 37 · 2022: 39 · 2021: 42 · 2020: 39 · 2019: 51 · 2018: 26 · 2017: 22 · 2016: 8
- FWCI
- 28.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1 TR00040)
- National Institute of Diabetes and Digestive and Kidney Diseases (UL1 TR00040, P30DK026687, P30DK072476)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- ketogenic diet, isocaloric diet, energy expenditure, body composition, obesity, overweight men, respiratory quotient, fat oxidation, fat-free mass loss, protein utilization, weight loss
- MeSH terms
- Adipose Tissue, Adult, Body Composition, Energy Intake, Dietary Carbohydrates, Dietary Fats, Energy Metabolism, Humans, Male, Obesity, Weight Loss, Overweight, Diet, Carbohydrate-Restricted, Diet, Ketogenic
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