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Underweight but not underfat: is fat-free mass a key factor in constitutionally thin women?

Abstract

Constitutional thinness is defined as a state of severe underweight with a body mass index similar to anorectic patients (BMI < 17.5 kg/m2), in the absence of any eating disorders or other obvious disruptive factors impacting energy balance. The analysis of body composition is essential as a first approach to characterize constitutional thinness and might help identify new discriminating differences between constitutional thinness and anorexia nervosa. A meta-analytical approach was performed to compare body composition of constitutionally thin, anorectic, and normal-weight subjects from all available studies found in the literature. The statistical analysis was carried out on large sample sizes: n = 205 females with constitutional thinness, n = 228 normal-weight control females, and n = 258 females with anorexia nervosa. Despite being as underweight as anorectic patients, constitutionally thin participants paradoxically presented higher percentages of fat mass than anorectic patients (18.9% vs. 11.4%, respectively; SMD [95% CI]: 1.62 [1.16; 2.08]), even found in the normal healthy ranges. Constitutionally thin people, however, display as low fat-free mass as anorectic patients. These observations question the use of high-fat diets in this population and bring new insights for nutrition and/or training strategies directed toward muscle mass gain. The present results give new elements to further distinguish constitutional thinness from anorexia nervosa and reinforce the need to better investigate the atypical phenotype of constitutional thinness.

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Fig. 1
Fig. 2: Fat mass percentage, body weight, body mass index, and fat-free mass comparisons between patients with anorexia nervosa, constitutionally thin people and normal-weight participants.

References

  1. 1.

    Grafe E. Constitutional undernutrition of doubtful origin (Chapter VIII). In: Metabolic diseases and their treatment. Lea & Febiger, Philadelphia; 1933. p. 211–2.

  2. 2.

    Germain N, Galusca B, Caron-Dorval D, Martin J-F, Pujos-Guillot E, Boirie Y, et al. Specific appetite, energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness. Nutr Diabetes. 2014;4:e126.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Ling Y, Galusca B, Hager J, Feasson L, Valsesia A, Epelbaum J, et al. Rational and design of an overfeeding protocol in constitutional thinness: understanding the physiology, metabolism and genetic background of resistance to weight gain. Annales d’Endocrinologie. 2016;77:563–9.

    PubMed  Article  Google Scholar 

  4. 4.

    Estour B, Galusca B, Germain N. Constitutional thinness and anorexia nervosa: a possible misdiagnosis? Front Endocrinol (Lausanne). 2014;5:175.

    Article  Google Scholar 

  5. 5.

    Estour B, Marouani N, Sigaud T, Lang F, Fakra E, Ling Y, et al. Differentiating constitutional thinness from anorexia nervosa in DSM 5 era. Psychoneuroendocrinology. 2017;84:94–100.

    PubMed  Article  Google Scholar 

  6. 6.

    Galusca B, Verney J, Meugnier E, Ling Y, Edouard P, Feasson L, et al. Reduced fibre size, capillary supply and mitochondrial activity in constitutional thinness’ skeletal muscle. Acta Physiol (Oxf). 2018;224:e13097.

    CAS  Article  Google Scholar 

  7. 7.

    Tolle V, Kadem M, Bluet-Pajot M-T, Frere D, Foulon C, Bossu C, et al. Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab. 2003;88:109–16.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Tagami T, Satoh N, Usui T, Yamada K, Shimatsu A, Kuzuya H. Adiponectin in anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab. 2004;89:1833–7.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Miljic D, Pekic S, Djurovic M, Doknic M, Milic N, Casanueva FF, et al. Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol release in patients with anorexia nervosa. J Clin Endocrinol Metab. 2006;91:1491–5.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Bossu C, Galusca B, Normand S, Germain N, Collet P, Frere D, et al. Energy expenditure adjusted for body composition differentiates constitutional thinness from both normal subjects and anorexia nervosa. Am J Physiol Endocrinol Metab. 2007;292:E132–7.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Germain N, Galusca B, Le Roux CW, Bossu C, Ghatei MA, Lang F, et al. Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin. Am J Clin Nutr. 2007;85:967–71.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Santonicola A, Siniscalchi M, Capone P, Gallotta S, Ciacci C, Iovino P. Prevalence of functional dyspepsia and its subgroups in patients with eating disorders. World J Gastroenterol. 2012;18:4379–85.

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Gunes A, Yıldırım Bas F, Arslan B, Tok L, Tok Ö, Salman Z. Assessment of corneal parameters in patients with constitutional thinness using scheimpflug imaging. Semin Ophthalmol. 2016;33:175–8.

    PubMed  Google Scholar 

  14. 14.

    Bailly M, Germain N, Féasson L, Costes F, Estour B, Hourdé C, et al. Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile. Appl Physiol Nutr Metab. 2020;45:1287–98.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Ling Y, Galusca B, Martin F-P, Bartova S, Carayol J, Moco S, et al. Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding. J Cachexia Sarcopenia Muscle. 2020;11:1187–99.

    PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Marra M, Pasanisi F, Montagnese C, De Filippo E, De Caprio C, de Magistris L, et al. BMR variability in women of different weight. Clin Nutr. 2007;26:567–72.

    PubMed  Article  Google Scholar 

  17. 17.

    Marra M, Caldara A, Montagnese C, De Filippo E, Pasanisi F, Contaldo F, et al. Bioelectrical impedance phase angle in constitutionally lean females, ballet dancers and patients with anorexia nervosa. Eur J Clin Nutr. 2009;63:905–8.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Pasanisi F, Pace L, Fonti R, Marra M, Sgambati D, De Caprio C, et al. Evidence of brown fat activity in constitutional leanness. J Clin Endocrinol Metab. 2013;98:1214–8.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Florent V, Baroncini M, Jissendi-Tchofo P, Lopes R, Vanhoutte M, Rasika S. et al. Hypothalamic structural and functional imbalances in anorexia nervosa. Neuroendocrinology. 2019;110:552–62.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Marra M, Sammarco R, De Filippo E, De Caprio C, Speranza E, Contaldo F, et al. Resting energy expenditure, body composition and phase angle in anorectic, ballet dancers and constitutionally lean males. Nutrients. 2019;11:502.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  21. 21.

    Ling Y, Carayol J, Galusca B, Canto C, Montaurier C, Matone A, et al. Persistent low body weight in humans is associated with higher mitochondrial activity in white adipose tissue. Am J Clin Nutr. 2019;110:605–16.

    PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Hasegawa A, Usui C, Kawano H, Sakamoto S, Higuchi M. Characteristics of body composition and resting energy expenditure in lean young women. J Nutr Sci Vitaminol. 2011;57:74–9.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Galusca B, Zouch M, Germain N, Bossu C, Frere D, Lang F, et al. Constitutional thinness: unusual human phenotype of low bone quality. J Clin Endocrinol Metab. 2008;93:110–7.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Bailly M, Germain N, Galusca B, Courteix D, Thivel D, Verney J. Definition and diagnosis of constitutional thinness: a systematic review. Br J Nutr. 2020;124:531–47.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Zurlo F, Larson K, Bogardus C, Ravussin E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Investig. 1990;86:1423.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Müller MJ, Bosy-Westphal A, Later W, Haas V, Heller M. Functional body composition: insights into the regulation of energy metabolism and some clinical applications. Eur J Clin Nutr. 2009;63:1045–56.

    PubMed  Article  Google Scholar 

  27. 27.

    Germain N, Galusca B, Grouselle D, Frere D, Tolle V, Zizzari P, et al. Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa. Psychoneuroendocrinology. 2009;34:413–9.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Galusca B, Jeandel L, Germain N, Alexandre D, Leprince J, Anouar Y, et al. Orexigenic neuropeptide 26RFa: new evidence for an adaptive profile of appetite regulation in anorexia nervosa. J Clin Endocrinol Metab. 2012;97:2012–8.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Galusca B, Prévost G, Germain N, Dubuc I, Ling Y, Anouar Y, et al. Neuropeptide Y and α-MSH circadian levels in two populations with low body weight: anorexia nervosa and constitutional thinness. PLoS ONE. 2015;10:e0122040.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  30. 30.

    Germain N, Viltart O, Loyens A, Bruchet C, Nadin K, Wolowczuk I, et al. Interleukin-7 plasma levels in human differentiate anorexia nervosa, constitutional thinness and healthy obesity. PLoS ONE. 2016;11:e0161890.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  31. 31.

    Guy-Grand B, Basdevant A. Etiopathogenesis and general orientation in the diagnosis of thinness. Rev Prat. 1982;32:237–43.

    CAS  PubMed  Google Scholar 

  32. 32.

    Apfelbaum M, Sachet P. Constitutional thinness. Rev Prat. 1982;32:245–7.

    CAS  PubMed  Google Scholar 

  33. 33.

    Jeukendrup A, Gleeson M. Normal ranges of body weight and body fat. In: Sport nutrition. Human Kinetics Publishers, Illinois; 2010. p. 488.

  34. 34.

    Branco BHM, Bernuci MP, Marques DC, Carvalho IZ, Barrero CAL, de Oliveira FM, et al. Proposal of a normative table for body fat percentages of Brazilian young adults through bioimpedanciometry. J Exerc Rehabil. 2018;14:974–9.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Nelson KM, Weinsier RL, Long CL, Schutz Y. Prediction of resting energy expenditure from fat-free mass and fat mass. Am J Clin Nutr. 1992;56:848–56.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Bosy-Westphal A, Müller MJ, Boschmann M, Klaus S, Kreymann G, Lührmann PM, et al. Grade of adiposity affects the impact of fat mass on resting energy expenditure in women. Br J Nutr. 2009;101:474–7.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Ostlund RE, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab. 1996;81:3909–13.

    CAS  PubMed  Google Scholar 

  38. 38.

    Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007;8:21–34.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Blundell JE, Goodson S, Halford JC. Regulation of appetite: role of leptin in signalling systems for drive and satiety. Int J Obes Relat Metab Disord. 2001;25(Suppl 1):S29–34.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Karageorgiou V, Furukawa TA, Tsigkaropoulou E, Karavia A, Gournellis R, Soureti A, et al. Adipokines in anorexia nervosa: a systematic review and meta-analysis. Psychoneuroendocrinology. 2020;112:104485.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y. Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index. Am J Clin Nutr. 2000;72:694–701.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Dulloo AG, Jacquet J, Miles-Chan JL, Schutz Y. Passive and active roles of fat-free mass in the control of energy intake and body composition regulation. Eur J Clin Nutr. 2016;71:353–7.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Dulloo AG, Miles-Chan JL, Schutz Y. Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition. Eur J Clin Nutr. 2018;72:657–64.

    PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Dulloo AG, Jacquet J, Solinas G, Montani J-P, Schutz Y. Body composition phenotypes in pathways to obesity and the metabolic syndrome. Int J Obes (Lond). 2010;34(Suppl 2):S4–17.

    Article  Google Scholar 

  45. 45.

    Verney J, Schwartz C, Amiche S, Pereira B, Thivel D. Comparisons of a multi-frequency bioelectrical impedance analysis to the dual-energy X-ray absorptiometry scan in healthy young adults depending on their physical activity level. J Hum Kinet. 2015;47:73–80.

    PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Velazquez-Alva MDC, Irigoyen-Camacho ME, Huerta-Huerta R, Delgadillo-Velazquez J. A comparison of dual energy x-ray absorptiometry and two bioelectrical impedance analyzers to measure body fat percentage and fat-free mass index in a group of Mexican young women. Nutr Hosp. 2014;29:1038–46.

    Google Scholar 

  47. 47.

    Thivel D, Verney J, Miguet M, Masurier J, Cardenoux C, Lambert C, et al. The accuracy of bioelectrical impedance to track body composition changes depends on the degree of obesity in adolescents with obesity. Nutr Res. 2018;54:60–8.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Gade J, Astrup A, Vinther A, Zerahn B. Comparison of a dual-frequency bio-impedance analyser with dual-energy X-ray absorptiometry for assessment of body composition in geriatric patients. Clin Physiol Funct Imaging. 2020;40:290–301.

    PubMed  Article  Google Scholar 

  49. 49.

    Ayvaz G. Methods for body composition analysis in adults. TOOBESJ. 2011;3:62–9.

    Article  Google Scholar 

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Conceptualization: DT and JV; Process of screening and selection of publications: MB, JV, and DT; Data extraction: MB and AB; Statistical analyses: BP; Writing the article: MB and AB; Supervision and revision of the article: JV, DT, NG, BG, DC, and YB.

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Correspondence to Mélina Bailly.

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Bailly, M., Boscaro, A., Pereira, B. et al. Underweight but not underfat: is fat-free mass a key factor in constitutionally thin women?. Eur J Clin Nutr (2021). https://doi.org/10.1038/s41430-021-00895-5

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