Multi-component molecular-level body composition reference methods: evolving concepts and future directions.
Open accessAbstract
Excess adiposity is the main phenotypic feature that defines human obesity and that plays a pathophysiological role in most chronic diseases. Measuring the amount of fat mass present is thus a central aspect of studying obesity at the individual and population levels. Nevertheless, a consensus is lacking among investigators on a single accepted 'reference' approach for quantifying fat mass in vivo. While the research community generally relies on the multi-component body volume class of 'reference' models for quantifying fat mass, no definable guide discerns among different applied equations for partitioning the four (fat, water, protein and mineral mass) or more quantified components, standardizes 'adjustment' or measurement system approaches for model-required labelled water dilution volumes and bone mineral mass estimates, or firmly establishes the body temperature at which model physical properties are assumed. The resulting differing reference strategies for quantifying body composition in vivo leads to small, but under some circumstances, important differences in the amount of measured body fat. Recent technological advances highlight opportunities to expand model applications to new subject groups and measured components such as total body protein. The current report reviews the historical evolution of multi-component body volume-based methods in the context of prevailing uncertainties and future potential.
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The four-compartment model is the most suitable reference method to assess FM and FFM at the molecular level.
“Although DXA cannot be considered the gold standard for the determination of FFM at the molecular level, and the four-compartment model (4C) is the most suitable reference method to assess FM and FFM at the molecular level (12), due to the complexity of the technique (13), the use of DXA to derive BIA equations has been widely accepted (14, 15).”
From Development and Cross-Validation of a Predictive Equation for Fat-Free Mass in Brazilian Adolescents by Bioelectrical Impedance (2022) · cites this paper as [12]
The Body Volume Approach section (page unavailable) says the four-component model improves the accuracy of body-fat estimates over two- and three-component models. But the Conclusions (page unavailable) say there is no agreed reference or gold-standard method. The paper therefore supports using the model as a reference for fat mass, not the stronger claim that it is the most suitable method for both FM and FFM. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe 4C model is the most appropriate reference method for assessing FM and FFM at the molecular level.
“The 4C model is the most appropriate reference method for assessing FM and FFM at the molecular level (12).”
From Development and Cross-Validation of a Predictive Equation for Fat-Free Mass in Brazilian Adolescents by Bioelectrical Impedance (2022) · cites this paper as [12]
The Body Volume Approach section says the four-component model improves the accuracy of body-fat estimates over two- and three-component models. But the Conclusions state that there is no agreed reference or gold-standard method, so the paper does not establish the 4C model as the most appropriate method for assessing FM and FFM. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDXA cannot be considered the gold standard for the determination of FFM at the molecular level.
“Although DXA cannot be considered the gold standard for the determination of FFM at the molecular level, and the four-compartment model (4C) is the most suitable reference method to assess FM and FFM at the molecular level (12), due to the complexity of the technique (13), the use of DXA to derive BIA equations has been widely accepted (14, 15).”
From Development and Cross-Validation of a Predictive Equation for Fat-Free Mass in Brazilian Adolescents by Bioelectrical Impedance (2022) · cites this paper as [12]
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“…for determining FFM and FM. Additionally, the use of multi-components models allows for the breakdown of FFM into different parts such as total body water (TBW), intra (ICW) and extracellular water (ECW), body cell mass (BCM), lean soft mass (LSM), skeletal muscle mass (SMM), and bone mass [7, 8].”
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Self-citation
- Authors
- Heymsfield, S. B., Ebbeling, C. B., Zheng, J., Pietrobelli, A., Strauss, B. J., Silva, A. M., & Ludwig, D. S.
- Affiliations
- Pennington Biomedical Research Center (US)
- Boston Children's Hospital (US)
- University of Verona (IT)
- Salford Royal NHS Foundation Trust (GB)
- Centro Interdisciplinar de Estudo da Performance Humana (PT)
- Corresponding author
- Heymsfield, S. B.
- Venue
- Obesity Reviews
- Publisher
- Wiley
- Published
- 2015-02-03
- Volume
- 16
- Issue
- 4
- Pages
- 282-294
- ISSN
- 1467-7881 (ISSN-L)
- 1467-789X
- PMC
- PMC4464774
- OpenAlex
- W1594872287
- Cited by
- 111
- References
- 85
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 17 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 12 · 2015: 2
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Obesity Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK082730, P30DK040561)
- Topics
- Health Sciences › Medicine › Physiology › Body Composition Measurement Techniques
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- body composition, reference method, obesity, excess adiposity, bone mineral mass, body temperature, total body protein
- MeSH terms
- Body Composition, Body Water, Cadaver, Humans, Models, Biological, Obesity, Reference Values, Absorptiometry, Photon, Body Mass Index
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