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Lipid analyses in patient samples taken before and after initiation of amiodarone therapy showed a systematic increase of desmosterol upon drug administration, strongly arguing for a direct causal link between amiodarone and desmosterol accumulation. Mechanistically, we found that amiodarone resulted in desmosterol accumulation in cultured human cells and that the compound directly inhibited the 24\u2010dehydrocholesterol reductase (DHCR24) enzyme activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These novel findings demonstrate that amiodarone blocks the cholesterol synthesis pathway by inhibiting DHCR24, causing a robust accumulation of cellular desmosterol in cells and in the sera of amiodarone\u2010treated patients. It is conceivable that the antiarrhythmic potential and side effects of amiodarone may in part result from inhibition of the cholesterol synthesis pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13095","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T14:38:50Z","timestamp":1589639930000},"page":"560-569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Amiodarone disrupts cholesterol biosynthesis pathway and causes accumulation of circulating desmosterol by inhibiting 24\u2010dehydrocholesterol reductase"],"prefix":"10.1111","volume":"288","author":[{"given":"P.","family":"Simonen","sequence":"first","affiliation":[{"name":"From the Heart and Lung Center Cardiology University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Stem Cells and Metabolism Research Program Faculty of Medicine University of Helsinki Helsinki Finland"},{"name":"Minerva Foundation Institute for Medical Research Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. 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