Statins are anti-inflammatory, no question about it. But how do they work in inflammation? In human cardiovascular diseases, endothelial dysfunction (ED) is an inflammatory pathological state of the inner lining of blood vessels (endothelium) that leads to cardiovascular disease. Normal functions of endothelial cells include facilitation of coagulation, platelet adhesion, immune function, and control of volume and electrolyte content in and out of the blood vessels. Both statins and vitamin D reduce this endothelial inflammation.
However, the cause of endothelial dysfunction is unknown. Endothelial dysfunction is present in about half of people with chest pain, even in the absence of overt blockages in large coronary arteries. Curiously, endothelial dysfunction is not predicted by typical risk factors for atherosclerosis, e.g., obesity, hypertension, high cholesterol, and smoking.
Endothelial dysfunction can be assessed in various ways. Vitamin D has been reported to be associated with endothelial function. In a small placebo controlled study, a single dose (100,000 IU) of vitamin D2 improved endothelial dysfunction (flow mediated vasodilation or FMD) before and after 8 weeks of administration of vitamin D2 in type 2 diabetic patients with vitamin D deficiency, even after adjusting for changes in blood pressure. Likewise, in patients with severe vitamin D deficiency endothelial dysfunction improved after 300,000 IU vitamin D3 over 3 months. Others have found that inadequate 25(OH)D levels are associated with worse endothelial dysfunction in healthy middle-aged/older adults.
Recently, Dr Christian Ott and colleagues of the University of Erlangen-Nuremberg in Germany conducted a double-blind randomized controlled trial of 31 patients with high cholesterol who also had vitamin D insufficiency (25(OH)D <30 ng/ml).
Ott C, Raff U, Schneider MP, Titze SI, Schmieder RE.25-Hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment. Clin Res Cardiol. 2012 Dec 21.
The scientists assigned half of the patients to get 10 mg/day of Crestor for 6 weeks and the other half got placebo. Analysis revealed that baseline vitamin D levels were an independent determinant of endothelial dysfunction. In other words, low vitamin D levels were associated with more dysfunction.
After the course of treatment, compared to placebo, Crestor treatment significantly increased 25(OH)D levels, a frequently replicated finding. Endothelial dysfunction was significantly better after 6 weeks of Crestor than after placebo (p = 0.044).
The authors concluded,
“Our present observations indicate that vitamin D deficiency is independently associated with impaired endothelial function in the renal vasculature, and rosuvastatin (Crestor) treatment beneficially influenced vitamin D levels and associated impaired renal endothelial function.”
To my knowledge, this is the first study to directly implicate vitamin D improving endothelial dysfunction as the mechanism of action of the statins. However, there is no known explanation for the mechanism by which statins increase vitamin D levels, but virtually all studies on statins show that they do.
Cholesterol and vitamin D have the same pre cursor, namely 7-dehydrocholesterol, but the precise interaction and regulation are not known. Perhaps statins somehow increase the level of 7-dehydrocholesterol available for synthesis of vitamin D in the skin. So far, studies failed to demonstrate that statins activate the vitamin D receptor.
If the simplest explanation is the best, it is that the anti-inflammatory mechanism of action of the statins may be to simply raise vitamin D levels. While we need more research, if this is indeed the case that statins work by increasing vitamin D levels, there are better ways to raise you vitamin D levels than taking statins, although I am confronting a multi-billion dollar business.