Statins are some of the most widely prescribed drugs in the world. Their use has expanded into many areas such as autoimmune disorders, cancer, obesity, and Alzheimer’s disease. However, it is cholesterol that drives the statin market. The US market for statins nearly tripled when the National Cholesterol Education Program (NCEP) revised its guidelines to recommend statins as primary prevention. Although the NCEP panel cited randomized trials to support statin therapy for primary prevention of occlusive cardiovascular disease, a report in Lancet questioned the conclusion.
Journalists have also questioned the interests of the doctors who made the NCEP recommendations, as 8 of the 9 doctors on the NCEP panel were discovered to have been paid by statin manufacturers. Pfizer’s Lipitor was the world’s top-selling medicine last year, with sales of $13.3 billion. AstraZeneca’s Crestor, which made $5.38 billion in sales during 2009, is one of the company’s bestselling medicines.
How do statins work? We know they inhibit an enzyme involved in the production of cholesterol. However, if that is their mechanism of action, why didn’t the five previous classes of lipid lowering drugs work? Maybe the stains work in another way, one shown repeatedly in scientific trials. That is, perhaps statins raise vitamin D levels. I count eight studies that looked at the issue:
Lovastatin (Mevacor, Altocor, Altoprev):
- Wilczek H, Sobra J, Justová V, Ceska R, Jůzová Z, Procházková R, Kvasilová M, Pacovský V. [Iatropathogenic effect of Mevacor on vitamin D metabolism]. Cas Lek Cesk. 1989 Sep 29;128(40):1254-6. Czech.
Simvastatin (Zocor, Lipex):
- Liberopoulos EN, Makariou SE, Moutzouri E, Kostapanos MS, Challa A, Elisaf M. Effect of Simvastatin/Ezetimibe 10/10 mg Versus Simvastatin 40 mg on Serum Vitamin D Levels. J Cardiovasc Pharmacol Ther. 2013 Jan 2.
- Wilczek H, Sobra J, Ceska R, Justová V, Jůzová Z, Procházková R, Kvasilová M. [Monitoring plasma levels of vitamin D metabolites in simvastatin (Zocor) therapy in patients with familial hypercholesterolemia]. Cas Lek Cesk. 1994 Dec 5;133(23):727-9. Czech.
- Rejnmark L, Vestergaard P, Heickendorff L, Mosekilde L. Simvastatin does not affect vitamin d status, but low vitamin d levels are associated with dyslipidemia: results from a randomised, controlled trial. Int J Endocrinol. 2010;2010:957174.
- Yavuz B, Ertugrul DT, Cil H, Ata N, Akin KO, Yalcin AA, Kucukazman M, Dal K, Hokkaomeroglu MS, Yavuz BB, Tutal E. Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther. 2009 Aug;23(4):295-9.
- Ertugrul DT, Yavuz B, Cil H, Ata N, Akin KO, Kucukazman M, Yalcin AA, Dal K, Yavuz BB, Tutal E. STATIN-D Study: Comparison of the Influences of Rosuvastatin and Fluvastatin Treatment on the Levels of 25 Hydroxyvitamin D. Cardiovasc Ther. 2010 Mar 27.
- Makariou SE, Liberopoulos EN, Agouridis AP, Challa A, Elisaf M. Effect of rosuvastatin monotherapy and in combination with fenofibrate or omega-3 fatty acids on serum vitamin D levels. J Cardiovasc Pharmacol Ther. 2012 Dec;17(4):382-6.
- Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A. Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol. 2007 Apr 1;99(7):903-5. Epub 2007 Feb 8.
All but one of the eight studies shows the same thing: statins raise vitamin D levels. Is that there true mechanism of action?