Can LDL cholesterol be too low? Possible risks of extremely low levels

A. G. Olsson, B. Angelin, G. Assmann, C. J. Binder, I. Björkhem, A. Cedazo-Minguez, J. Cohen, A. von Eckardstein, E. Farinaro, D. Müller-Wieland, K. G. Parhofer, P. Parini, R. S. Rosenson, J. Starup-Linde, M. J. Tikkanen, L. Yvan-Charvet

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood–brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important.

Original languageEnglish (US)
Pages (from-to)534-553
Number of pages20
JournalJournal of Internal Medicine
Volume281
Issue number6
DOIs
StatePublished - Jun 1 2017

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LDL Cholesterol
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
VLDL Cholesterol
Inborn Genetic Diseases
Rare Diseases
Drug-Related Side Effects and Adverse Reactions
Bile Acids and Salts
Lipid Metabolism
Type 2 Diabetes Mellitus
Cognition
Communicable Diseases
Cardiovascular Diseases
Central Nervous System
Steroids
Clinical Trials
Hormones
Depression
Neoplasms
Therapeutics

Keywords

  • abetalipoproteinaemia
  • adverse effects
  • hypocholesterolaemia
  • low-density lipoprotein
  • safety

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Olsson, A. G., Angelin, B., Assmann, G., Binder, C. J., Björkhem, I., Cedazo-Minguez, A., ... Yvan-Charvet, L. (2017). Can LDL cholesterol be too low? Possible risks of extremely low levels. Journal of Internal Medicine, 281(6), 534-553. https://doi.org/10.1111/joim.12614

Can LDL cholesterol be too low? Possible risks of extremely low levels. / Olsson, A. G.; Angelin, B.; Assmann, G.; Binder, C. J.; Björkhem, I.; Cedazo-Minguez, A.; Cohen, J.; von Eckardstein, A.; Farinaro, E.; Müller-Wieland, D.; Parhofer, K. G.; Parini, P.; Rosenson, R. S.; Starup-Linde, J.; Tikkanen, M. J.; Yvan-Charvet, L.

In: Journal of Internal Medicine, Vol. 281, No. 6, 01.06.2017, p. 534-553.

Research output: Contribution to journalArticle

Olsson, AG, Angelin, B, Assmann, G, Binder, CJ, Björkhem, I, Cedazo-Minguez, A, Cohen, J, von Eckardstein, A, Farinaro, E, Müller-Wieland, D, Parhofer, KG, Parini, P, Rosenson, RS, Starup-Linde, J, Tikkanen, MJ & Yvan-Charvet, L 2017, 'Can LDL cholesterol be too low? Possible risks of extremely low levels', Journal of Internal Medicine, vol. 281, no. 6, pp. 534-553. https://doi.org/10.1111/joim.12614
Olsson AG, Angelin B, Assmann G, Binder CJ, Björkhem I, Cedazo-Minguez A et al. Can LDL cholesterol be too low? Possible risks of extremely low levels. Journal of Internal Medicine. 2017 Jun 1;281(6):534-553. https://doi.org/10.1111/joim.12614
Olsson, A. G. ; Angelin, B. ; Assmann, G. ; Binder, C. J. ; Björkhem, I. ; Cedazo-Minguez, A. ; Cohen, J. ; von Eckardstein, A. ; Farinaro, E. ; Müller-Wieland, D. ; Parhofer, K. G. ; Parini, P. ; Rosenson, R. S. ; Starup-Linde, J. ; Tikkanen, M. J. ; Yvan-Charvet, L. / Can LDL cholesterol be too low? Possible risks of extremely low levels. In: Journal of Internal Medicine. 2017 ; Vol. 281, No. 6. pp. 534-553.
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AU - Cedazo-Minguez, A.

AU - Cohen, J.

AU - von Eckardstein, A.

AU - Farinaro, E.

AU - Müller-Wieland, D.

AU - Parhofer, K. G.

AU - Parini, P.

AU - Rosenson, R. S.

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