A randomized controlled trial published in the Journal of Clinical Pharmacology found that the treatment of vitamin D deficiency enhanced the anticoagulant effect of warfarin in patients with thromboembolism.
Thromboembolism occurs when a clot (thrombus) forms in a blood vessel and breaks loose into the blood stream to plug another vessel. The clot may clog a blood vessel in the lungs (pulmonary embolism), brain (stroke), kidneys, leg (deep vein thrombosis) or gastrointestinal tract. Thromboembolisms affect approximately 900,000 people and are responsible for up to 100,000 American deaths each year in the treatments for thromboembolisms involve anticoagulants (blood thinners), aspirin or vasodilators.
Research has found that vitamin D deficiency is extremely prevalent among patients with thrombosis. In fact, research suggests that vitamin D deficiency may be a risk factor for the development of cardiovascular disease.
Heart muscle cells and blood vessel walls contain vitamin D receptors. Scientists believe that vitamin D is likely involved with thrombosis due to its role in inflammation. Inflammation is a large risk factor for the development of thrombosis. C-reactive protein (CRP), a common marker of inflammation, can increase the blood clotting activity of tissue factor (TF). Furthermore, interaction of TF with P-selectin (an adhesion molecule) has been shown to accelerate clotting. Therefore, P-selectin is considered a pro-coagulant element and is considered one of the most accurate markers for thrombosis.
Few studies have been conducted evaluating the relationship between vitamin D and thrombosis. Although limited, the current evidence leads researchers to believe vitamin D may possess anticoagulant properties. For example, a randomized controlled trial reported a significantly lower incidence of thrombotic events in cancer patients who took active vitamin D compared to those who were given placebo. No studies have evaluated the impact of treating vitamin D deficiency for the improvement of thrombosis.
In a recent randomized controlled trial, researchers aimed to evaluate the effects of treating vitamin D deficiency on CRP and P-selectin levels. To do this, the researchers divided 70 vitamin D deficient (< 30 ng/ml) patients with deep vein thrombosis or pulmonary embolism into two groups: a treatment group and a control group. The treatment group received 50,000 IU of vitamin D3 weekly for 8 weeks followed by 50,000 IU every two weeks for four more weeks. The control group did not receive any supplementation.
P-selectin, CRP and vitamin D status were measured at baseline, one and three months after the intervention. The researchers wanted to know whether vitamin D supplementation would reduce P-selectin and hs-CRP levels. As a secondary outcome, the researchers assessed the doses of warfarin, an anti-coagulant, among the patients. Here is what the researchers found:
- The average baseline vitamin D levels were 15.3 ng/ml and 15.5 ng/ml in the treatment and control groups, respectively.
- After one month of vitamin D supplementation, the treatment group’s vitamin D levels increased from an average of 15.3 ng/ml to 62.5 ng/ml (p = 0.006).
- After three months of supplementing, the treatment’s group increased to 73.2 ng/ml (p = 0.001).
- There was no significant decrease in CRP levels (p = 0.525).
- P-selectin decreased after three months, but this difference was not significant (p = 0.230).
- Those who were given vitamin D used significantly lower warfarin doses than those who were not treated (p = 0.03).
The researchers stated,
“The results indicated that treatment of vitamin D deficiency had no significant effect on [CRP] or P-selectin after 3 months follow up period among patients with deep vein [thrombosis/pulmonary embolism]. However, treatment of vitamin D deficiency in [thromboembolism] patients resulted in lower doses of warfarin.”
They continued to state,
“This observation is the first clinical report of enhancement of anticoagulant effect of warfarin by supplementing of vitamin D.”
The RCT design allowed for the study to prove causality. However, the study presented results that were contrary to previous research findings, concluding that vitamin D supplementation did not reduce CRP levels. Thus, further research is needed to clarify the role of vitamin D for CRP levels in thromboembolism patients. Most importantly, the study suggests that vitamin D supplementation may improve the efficacy of warfarin for patients with thromboembolism.
Tovey, A. & Cannell, JJ. Pilot RCT discovers vitamin D supplementation may enhance the effect of blood thinners for blood clots. The Vitamin D Council Blog & Newsletter, 2016.
Hejazi, M. et al. The effect of treatment of vitamin D deficiency on the level of P-selectin and hs-CRP in patients with thromboembolism; a pilot randomized clinical trial . Journal of Clinical Pharmacology, 2016.