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Metabolism and Metabolomics

Are methods of estimating fat-free mass loss with energy-restricted diets accurate?



Fat-free mass (FFM) often serves as a body composition outcome variable in weight loss studies. An important assumption is that the proportions of components that make up FFM remain stable following weight loss; some body composition models rely on these “constants”. This exploratory study examined key FFM component proportions before and following weight loss in two studies of participants with overweight and obesity.


201 men and women consumed calorie-restricted moderate- or very-low carbohydrate diets leading to 10–18% weight loss in 9–15 weeks. Measured total body fat, lean mass, bone mineral, total body water (TBW), and body weight at baseline and follow-up were used to derive FFM and its chemical proportions using a four-component model.


A consistent finding in both studies was a non-significant reduction in bone mineral and a corresponding increase (p < 0.001) in bone mineral/FFM; FFM density increased significantly in one group of women and in all four participant groups combined (both, p < 0.05). FFM hydration (TBW/FFM) increased in all groups of men and women, one significantly (p < 0.01), and in the combined sample (borderline, p < 0.10). The proportion of FFM as protein decreased across all groups, two significantly (p < 0.05–0.01) and in the combined sample (p < 0.05).


FFM relative proportions of chemical components may not be identical before and after short-term weight loss, an observation impacting some widely used body composition models and methods. Caution is thus needed when applying FFM as a safety signal or to index metabolic evaluations in clinical trials when these body composition approaches are used.

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Fig. 1: Qualitative depiction of changes in FFM chemical component composition with weight loss.

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Data availability

Data described in this manuscript will be made available upon request and approval by the investigators.


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(FS)2 was supported by grants from Nutrition Science Initiative (made possible by gifts from Arnold Ventures and Robert Lloyd Corkin Charitable Foundation), New Balance Foundation, Many Voices Foundation, and Blue Cross Blue Shield. FB4 was supported by a grant from Arnold Ventures.

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Authors and Affiliations



CBE, JMWW, and DSL designed research; SBH, CE, JMWW, and DSL conducted research; CE and DSL provided essential materials; SBH, CE, JMWW, CM, MH, and JS analyzed data; SBH, CE, JMMWW, CM, MH, JS, and DSL wrote the paper and had primary responsibility for final content.

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Correspondence to Steven B. Heymsfield.

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Competing interests

Dr. Heymsfield reports his role on the Medical Advisory Boards of Tanita Corporation, Amgen, and Medifast; he is also an Amazon Scholar. DSL received royalties for books that recommend a low-glycemic load diet; his spouse owns a nutrition education and consulting business.

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Protocols for FB4 and (FS)2 were approved by the Institutional Review Board at Boston Children’s Hospital and written informed consent was obtained from all participants.

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Heymsfield, S.B., Ludwig, D.S., Wong, J.M.W. et al. Are methods of estimating fat-free mass loss with energy-restricted diets accurate?. Eur J Clin Nutr 77, 525–531 (2023).

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