Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study

Background: Whether vitamin supplements decrease venous thrombosis risk is controversial. Previous reports did not all take confounding fully into account, either by randomization or by extensive adjustment. Objective: The aim of our study was to determine whether vitamin supplementation decreases the risk of venous thrombosis. Design: A large case-control study included 2506 patients with venous thrombosis, 2506 partner controls, and 2684 random-digit dialing (RDD) controls. When patients were compared with RDD controls, unconditional logistic regression was used to calculate ORs with 95% CIs. When patients were compared with partner controls, conditional logistic regression was used, providing further adjustment for unmeasured confounding. Results: Vitamin use yielded a 37% lower risk of venous thrombosis than no vitamin use (OR: 0.63; 95% CI: 0.57, 0.70) when comparing patients with RDD controls. Adjustment for several putative confounders did not change the estimate (OR: 0.68; 95% CI: 0.61, 0.77). The fully adjusted ORs for vitamin A, vitamin B-6, vitamin B-12, folic acid, vitamin C, vitamin D, vitamin E, and multivitamin use were in the same range. However, when patients were compared with partner controls, ORs attenuated to unity. Results were similar for provoked and unprovoked events, as well as for deep vein thrombosis and pulmonary embolism. Conclusions: After extensive adjustments, vitamin supplementation was no longer associated with a decreased risk of venous thrombosis in this study. Previous positive results may have been spurious as a result of uncontrolled confounding.