Last week, we set the stage by breaking down the science behind cholesterol: how it moves through our body, why it causes disease, and when we discovered the link between LDL and atherosclerosis. This week, armed with that knowledge, we’re asking the big question: what do we do about high cholesterol? Statins emerged as a highly effective intervention but one that is not without its share of controversy and misinformation. We delve into the story and science of statins and other cholesterol-lowering drugs, from their brilliant discovery to early promising trials, from barriers preventing their use to the heaps of misinformation abounding on the internet. How do statins actually work? What does penicillin have to do with their discovery? What’s the deal with side effects? Tune in for all this and more.
| History | Biology |
| Al-Dalakta, Astefanos, et al. “Inaccurate information regarding cardiovascular disease prevention enabled by generative artificial intelligence.” American Journal of Preventive Cardiology 25 (2026): 101404. | Silverman, M.G., Ference, B.A., Im, K., Wiviott, S.D., Giugliano, R.P., Grundy, S.M., Braunwald, E. and Sabatine, M.S., 2016. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. Jama, 316(12), pp.1289-1297. |
| Bhandari, Buna, et al. “Misinformation on cardiovascular disease spreads through social networks: a scoping review.” BMJ Public Health 4.1 (2026). | Blumenthal, R.S., Morris, P.B., Gaudino, M., Johnson, H.M., Anderson, T.S., Bittner, V.A., Blankstein, R., Brewer, L.C., Cho, L., de Ferranti, S.D. and Gianos, E., 2026. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. JACC. |
| Chester, Adrian, and Ahmed El Guindy. “From Fleming to Endo: The discovery of statins.” Global cardiology science & practice 2021.4 (2021): e202132. | Global Burden of Cardiovascular Diseases and Risks 2023 Collaborators, 2025. Global, regional, and national burden of cardiovascular diseases and risk factors in 204 countries and territories, 1990-2023. Journal of the American College of Cardiology, 86(22), pp.2167-2243. |
| Reith, Christina, et al. “Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials.” The Lancet 400.10355 (2022): 832-845. | Reith, C., Baigent, C., Blackwell, L., Emberson, J., Spata, E., Davies, K., Halls, H., Holland, L., Wilson, K., Armitage, J. and Harper, C., 2022. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. The Lancet, 400(10355), pp.832-845. |
| Endo, Akira. “A gift from nature: the birth of the statins.” Nature medicine 14.10 (2008): 1050-1052. | Domanski, M.J., Tian, X., Wu, C.O., Reis, J.P., Dey, A.K., Gu, Y., Zhao, L., Bae, S., Liu, K., Hasan, A.A. and Zimrin, D., 2020. Time course of LDL cholesterol exposure and cardiovascular disease event risk. Journal of the American College of Cardiology, 76(13), pp.1507-1516. |
| Endo, Akira. “A historical perspective on the discovery of statins.” Proceedings of the Japan Academy, Series B 86.5 (2010): 484-493. | Duncan, M.S., Vasan, R.S. and Xanthakis, V., 2019. Trajectories of blood lipid concentrations over the adult life course and risk of cardiovascular disease and all‐cause mortality: observations from the Framingham study over 35 years. Journal of the American Heart Association, 8(11), p.e011433. |
| Johnson, Heather M. “The impact of health misinformation and health literacy on the management of dyslipidemia.” American Journal of Preventive Cardiology (2025): 101289. | Yusuf, S., Lonn, E., Pais, P., Bosch, J., Lopez-Jaramillo, P., Zhu, J., Xavier, D., Avezum, A., Leiter, L.A., Piegas, L.S. and Parkhomenko, A., 2016. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. New England Journal of Medicine, 374(21), pp.2032-2043. |
| Ju, Angela, et al. “Patient beliefs and attitudes to taking statins: systematic review of qualitative studies.” British Journal of General Practice (2018). | Kirkpatrick, C.F., Sikand, G., Petersen, K.S., Anderson, C.A., Aspry, K.E., Bolick, J.P., Kris-Etherton, P.M. and Maki, K.C., 2023. Nutrition interventions for adults with dyslipidemia: a clinical perspective from the National Lipid Association. Journal of clinical lipidology, 17(4), pp.428-451. |
| Klimov, Anatoli N., and Vladimir A. Nagornev. “Evolution of cholesterol concept of atherogenesis from Anitchkov to our days.” Pediatric Pathology & Molecular Medicine 21.3 (2002): 307-320. | Carter, S., Hill, A.M., Yandell, C., Wood, L., Coates, A.M. and Buckley, J.D., 2025. Impact of dietary cholesterol from eggs and saturated fat on LDL cholesterol levels: a randomized cross-over study. The American Journal of Clinical Nutrition, 122(1), pp.83-91. |
| Nelson, Adam J., Rishi Puri, and Steven E. Nissen. “Statins in a distorted mirror of media.” Current atherosclerosis reports 22.8 (2020): 37. | Hu, F.B. and Willett, W.C., 2002. Optimal diets for prevention of coronary heart disease. Jama, 288(20), pp.2569-2578. |
| Pedro-Botet, Juan, and Juan Rubiés-Prat. “Statin-associated muscle symptoms: beware of the nocebo effect.” The Lancet 389.10088 (2017): 2445-2446. | US Preventive Services Task Force, Mangione, C.M., Barry, M.J., Nicholson, W.K., Cabana, M., Chelmow, D., Coker, T.R., Davis, E.M., Donahue, K.E., Jaén, C.R. and Kubik, M., 2022. Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement. Jama, 328(8), pp.746-753. |
| Penson, Peter E., et al. “Introducing the ‘Drucebo’effect in statin therapy: a systematic review of studies comparing reported rates of statin‐associated muscle symptoms, under blinded and open‐label conditions.” Journal of Cachexia, Sarcopenia and Muscle 9.6 (2018): 1023-1033. | Rehberger Likozar, A., Zavrtanik, M. and Šebeštjen, M., 2020. Lipoprotein (a) in atherosclerosis: from pathophysiology to clinical relevance and treatment options. Annals of medicine, 52(5), pp.162-177. |
| Rea, Philip A. “Statins: From Fungus to Pharma: The curiosity of biochemists, mixed with some obvious economic incentives, created a family of powerful cardiovascular drugs.” American Scientist 96.5 (2008): 408-415. | Berger, S., Raman, G., Vishwanathan, R., Jacques, P.F. and Johnson, E.J., 2015. Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis. The American journal of clinical nutrition, 102(2), pp.276-294. |
| Schekman, Randy. “Discovery of the cellular and molecular basis of cholesterol control.” Proceedings of the National Academy of Sciences 110.37 (2013): 14833-14836. | Jeong, S.M., Choi, S., Kim, K., Kim, S.M., Lee, G., Park, S.Y., Kim, Y.Y., Son, J.S., Yun, J.M. and Park, S.M., 2018. Effect of change in total cholesterol levels on cardiovascular disease among young adults. Journal of the American Heart Association, 7(12), p.e008819. |
| Steinberg, Daniel. “The cholesterol controversy is over. Why did it take so long?.” Circulation 80.4 (1989): 1070-1078. | Wadhera, R.K., Steen, D.L., Khan, I., Giugliano, R.P. and Foody, J.M., 2016. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. Journal of clinical lipidology, 10(3), pp.472-489. |
| Steinberg, Daniel. “Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part I.” Journal of lipid research 45.9 (2004): 1583-1593. | Yusuf, S., Bosch, J., Dagenais, G., Zhu, J., Xavier, D., Liu, L., Pais, P., López-Jaramillo, P., Leiter, L.A., Dans, A. and Avezum, A., 2016. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. New England Journal of Medicine, 374(21), pp.2021-2031. |
| Steinberg, Daniel. “Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans.” Journal of lipid research 46.2 (2005): 179-190. | Chen, L., Chen, S., Bai, X., Su, M., He, L., Li, G., He, G., Yang, Y., Zhang, X., Cui, J. and Xu, W., 2024. Low-density lipoprotein cholesterol, cardiovascular disease risk, and mortality in China. JAMA network open, 7(7), p.e2422558. |
| Steinberg, Daniel. “An interpretive history of the cholesterol controversy, part III: mechanistically defining the role of hyperlipidemia.” J Lipid Res 46.10 (2005): 2037-2051. | Townsend, N., Kazakiewicz, D., Lucy Wright, F., Timmis, A., Huculeci, R., Torbica, A., Gale, C.P., Achenbach, S., Weidinger, F. and Vardas, P., 2022. Epidemiology of cardiovascular disease in Europe. Nature Reviews Cardiology, 19(2), pp.133-143. |
| Steinberg, Daniel. “Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost1.” Journal of Lipid Research 47.1 (2006): 1-14. | Marcus, M.E., Manne-Goehler, J., Theilmann, M., Farzadfar, F., Moghaddam, S.S., Keykhaei, M., Hajebi, A., Tschida, S., Lemp, J.M., Aryal, K.K. and Dunn, M., 2022. Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data. The Lancet Global Health, 10(3), pp.e369-e379. |
| Steinberg, Daniel. “Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the statins and the end of the controversy.” Journal of lipid research 47.7 (2006): 1339-1351. | Chobufo, M.D., Regner, S.R., Zeb, I., Lacoste, J.L., Virani, S.S. and Balla, S., 2022. Burden and predictors of statin use in primary and secondary prevention of atherosclerotic vascular disease in the US: from the National Health and Nutrition Examination Survey 2017–2020. European journal of preventive cardiology, 29(14), pp.1830-1838. |
| Stossel, Thomas P. “The discovery of statins.” Cell 134.6 (2008): 903-905. | Global Cardiovascular Risk Consortium, 2023. Global effect of modifiable risk factors on cardiovascular disease and mortality. New England Journal of Medicine, 389(14), pp.1273-1285. |
| Tabas, Ira. “Cholesterol in health and disease.” The Journal of clinical investigation 110.5 (2002): 583-590. | |
| Xie, Minjia, Seth S. Martin, and Alexander Turchin. “Reasons for non-acceptance of statin therapy by patients at high cardiovascular risk.” Scientific reports 15.1 (2025): 17014. |
Disclaimer: This post may contain affiliate links. If you buy something through one of these links, you won’t pay a penny more, but we’ll get a small commission which helps us keep things running. Thanks!
