Hypercholesterolemia in Underweight Individuals: Mechanisms, Clinical Significance and Practical Recommendations
DOI:
https://doi.org/10.12775/QS.2026.73.75089Keywords
anorexia nervosa, hypercholesterolemia, underweight, malnutrition, lipid metabolism, nutritional rehabilitationAbstract
Introduction. Hypercholesterolemia is typically associated with obesity and metabolic syndrome, yet elevated total and LDL cholesterol are also frequently observed in underweight individuals, including patients with anorexia nervosa (AN). This paradox can cause diagnostic uncertainty when lipid results are interpreted based on concepts derived from obesity-related dyslipidemia.
Aim. To summarize current evidence on mechanisms underlying hypercholesterolemia in underweight individuals, with emphasis on AN, and to outline its clinical significance and management.
Materials and Methods. A narrative review of PubMed and Google Scholar literature published up to July 2026, prioritizing systematic reviews, meta-analyses, and observational studies on lipid abnormalities in underweight populations.
Results. Hypercholesterolemia in starvation states arises from reduced hepatic LDL-receptor activity, a low-T3 endocrine state, altered cortisol, insulin and leptin signalling, impaired bile acid synthesis, and altered lipoprotein transport, rather than dietary cholesterol intake. These adaptations differ from obesity-driven dyslipidemia and generally improve with nutritional rehabilitation.
Conclusions. Hypercholesterolemia associated with underweight is usually a reversible metabolic adaptation to prolonged energy deficiency. Nutritional rehabilitation should be the primary treatment strategy, whereas persistent lipid abnormalities after weight restoration require further diagnostic evaluation.
References
1. Hussain AA, Hübel C, Hindborg M, Lindkvist E, Kastrup AM, Yilmaz Z, et al. Increased lipid and lipoprotein concentrations in anorexia nervosa: a systematic review and meta-analysis. Int J Eat Disord. 2019 Jun;52(6):611–29. https://doi.org/10.1002/eat.23051
2. Gizzi G, Cataldi S, Mazzeschi C, Delvecchio E, Ceccarini MR, Codini M, et al. Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk. Int J Mol Sci. 2022 Jul 5;23(13):7466. https://doi.org/10.3390/ijms23137466
3. Winston AP. The clinical biochemistry of anorexia nervosa. Ann Clin Biochem. 2012 Mar 1;49(2):132–43. https://doi.org/10.1258/acb.2011.011185
4. Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol. 2008 Feb;9(2):125–38. https://doi.org/10.1038/nrm2336
5. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990 Feb 1;343(6257):425–30. https://doi.org/10.1038/343425a0
6. Cost J, Krantz MJ, Mehler PS. Medical complications of anorexia nervosa. Cleve Clin J Med. 2020 Jun;87(6):361–6. https://doi.org/10.3949/ccjm.87a.19084
7. Iwan K, Bielak A, Gryta J, Janczewska M, Kalicka M, Kolasa A, et al. How do eating disorders can affect the endocrine system? - literature review. J Educ Health Sport. 2023 Jun 5;37(1):140–52. https://doi.org/10.12775/JEHS.2023.37.01.011
8. Klop B, Elte JWF, Cabezas MC. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients. 2013 Apr 12;5(4):1218–40. https://doi.org/10.3390/nu5041218
9. Brown MS, Goldstein JL. A Receptor-Mediated Pathway for Cholesterol Homeostasis. Science. 1986 Apr 4;232(4746):34–47. https://doi.org/10.1126/science.3513311
10. Weinbrenner T, Züger M, Jacoby G, Herpertz S, Liedtke R, Sudhop T, et al. Lipoprotein metabolism in patients with anorexia nervosa: a case–control study investigating the mechanisms leading to hypercholesterolaemia. Br J Nutr. 2004;91(6):959-969. https://doi.org/10.1079/BJN20041151
11. Rigaud D, Tallonneau I, Vergès B. Hypercholesterolaemia in anorexia nervosa: frequency and changes during refeeding. Diabetes Metab. 2009 Feb;35(1):57–63. https://doi.org/10.1016/j.diabet.2008.08.004
12. Ohwada R, Hotta M, Oikawa S, Takano K. Etiology of hypercholesterolemia in patients with anorexia nervosa. Int J Eat Disord. 2006 Nov;39(7):598–601. https://doi.org/10.1002/eat.20298
13. Westmoreland P, Krantz MJ, Mehler PS. Medical Complications of Anorexia Nervosa and Bulimia. Am J Med. 2016 Jan;129(1):30–7. https://doi.org/10.1016/j.amjmed.2015.06.031
14. Miller KK. Endocrine effects of anorexia nervosa. Endocrinol Metab Clin North Am. 2013 Sep;42(3):515–28. https://doi.org/10.1016/j.ecl.2013.05.007
15. NESTEL PJ. Cholesterol Metabolism in Anorexia Nervosa and Hypercholesterolemia. J Clin Endocrinol Metab. 1974 Feb 1;38(2):325–8. https://doi.org/10.1210/jcem-38-2-325
16. Gooding HC, de Ferranti SD. Cardiovascular risk assessment and cholesterol management in adolescents: getting to the heart of the matter. Curr Opin Pediatr. 2010 Aug;22(4):398–404. https://doi.org/10.1097/MOP.0b013e32833a6e22
17. Giovinazzo S, Sukkar SG, Rosa GM, Zappi A, Bezante GP, Balbi M, et al. Anorexia nervosa and heart disease: a systematic review. Eat Weight Disord EWD. 2019 Apr;24(2):199–207. https://doi.org/10.1007/s40519-018-0567-1
18. Mazurek K, Gęborys A, Wojcieszak M, Kania J, Miazga D, Maziarczyk A, et al. Systemic Consequences of Anorexia Nervosa: Multiorgan Disfunction and Long-Term Complications. Qual Sport. 2026 Feb 26;52:68741. https://doi.org/10.12775/QS.2026.52.68741
19. Buszek S, Widawska K, Bajak M, Czerniak P, Buszek J, Wajdowicz H, et al. Complications of anorexia nervosa - literature review. Qual Sport. 2024 Dec 13;35:56393. https://doi.org/10.12775/QS.2024.35.56393
20. Feillet F, Feillet-Coudray C, Bard JM, Parra HJ, Favre E, Kabuth B, et al. Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa. Clin Chim Acta. 2000 Apr 1;294(1):45–56. https://doi.org/10.1016/S0009-8981(99)00256-9
21. Diagnostic and statistical manual of mental disorders: DSM-5TM, 5th ed. Arlington, VA, US: American Psychiatric Publishing, Inc.; 2013. xliv, 947 p. (Diagnostic and statistical manual of mental disorders: DSM-5TM, 5th ed). https://doi.org/10.1176/appi.books.9780890425596
22. Mehler PS, Brown C. Anorexia nervosa – medical complications. J Eat Disord. 2015 Mar 31;3(1):11. https://doi.org/10.1186/s40337-015-0040-8
23. Morgan JF, Reid F, Lacey JH. The SCOFF questionnaire: assessment of a new screening tool for eating disorders. BMJ. 1999 Dec 4;319(7223):1467–8. https://doi.org/10.1136/bmj.319.7223.1467
24. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):e285–350. https://doi.org/10.1016/j.jacc.2018.11.003
25. Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, et al. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018 Aug 7;72(6):662–80. https://doi.org/10.1016/j.jacc.2018.05.044
26. Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008 Jun 28;336(7659):1495–8. https://doi.org/10.1136/bmj.a301
27. Marko N, Niewiadomska J, Furtak D, Grela W, Tulej D, Głogowska P, et al. Refeeding syndrome as a serious complication of a treatment of patients with anorexia nervosa - a literature review. J Educ Health Sport. 2025 Apr 3;80:58488. https://doi.org/10.12775/JEHS.2025.80.58488
28. 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 Oct;84:94–100. https://doi.org/10.1016/j.psyneuen.2017.06.015
29. Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, et al. The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S). Br J Sports Med. 2014 Apr;48(7):491–7. https://doi.org/10.1136/bjsports-2014-093502
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