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Hydroxychloroquine alters lipoprotein particle concentrations and composition.

Thiago B Mendes1, Rachel G Miller2, Frederico G S Toledo1

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Journal of Clinical Lipidology
|February 18, 2026
PubMed
Summary

Hydroxychloroquine (HCQ) significantly lowers total cholesterol and triglycerides by reducing LDL particle concentration and VLDL triglyceride content. It also alters HDL particle distribution, suggesting potential cardiovascular benefits.

Keywords:
Apolipoprotein AApolipoprotein BCholesterolHDLHydroxychloroquineIDLLDLParticle numberTriglycerideVLDL

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Lipid Metabolism

Background:

  • Hydroxychloroquine (HCQ) is an immunomodulatory drug used for autoimmune conditions.
  • Observational studies suggest HCQ may reduce cholesterol and triglyceride levels, implying cardiovascular benefits.
  • Detailed characterization of lipoprotein particle changes induced by HCQ is lacking.

Purpose of the Study:

  • To evaluate the impact of HCQ on circulating lipids.
  • To assess changes in lipoprotein concentration and composition.
  • To elucidate the mechanisms behind HCQ's lipid-modulating effects.

Main Methods:

  • Post hoc analysis of a randomized, placebo-controlled, double-blind trial.
  • Participants were adults at risk for type 2 diabetes.
  • Placebo-adjusted changes from baseline were analyzed using mixed-effects models, controlling for covariates.

Main Results:

  • HCQ reduced total cholesterol (10.4%), LDL cholesterol (12.9%), and non-HDL cholesterol (15.0%).
  • LDL particle concentration decreased by 15.1%, and ApoB by 9.7%.
  • Triglycerides fell by 27.8%, with reduced triglyceride content per VLDL particle; HDL composition shifted towards larger particles.

Conclusions:

  • HCQ modifies lipoprotein concentration and composition distinctly across lipoprotein classes.
  • The drug lowers total cholesterol via reduced LDL particle concentration.
  • HCQ decreases triglycerides by reducing VLDL triglyceride content and alters HDL size distribution, suggesting potential atheroprotective effects.