Studies have suggested that Vitamin E may lower the risk of cardiovascular events and microvascular complications in patients with diabetes mellitus. A recent study showed that Vitamin E might preferentially improve cardiovascular risk in haptoglobin 2-2 (Hp 2-2) genotype diabetes individuals. In a double-blind crossover study in Hp2-2 type 2 diabetes mellitus patients who were given 8weeks of daily Vitamin E 400 IU supplementation showed significant improvement in peripheral vascular function. Haptoglobin, Diabetes and Vitamin E Hp 2-2 diabetics represent a subgroup of patients who have increased oxidative stress. The Hp 2-2 proteins do not adequately control the oxidative stress in these patients. In this subgroup of patients, a high dose of Vitamin E may have a beneficial effect. HOPE Trial In the Heart Outcomes Prevention Evaluation (HOPE) study, the influence of Vitamin E supplementation (400 IU/day) or placebo was assessed in 9,541 men and women. The participants included in the study had cardiovascular disease, diabetes and an additional risk factor. After a follow-up of approximately 4.5 years, the results revealed that Hp 2-2 individuals with diabetes receiving Vitamin E benefitted from this treatment. The Vitamin E treated patients exhibited an approximately 50% statistically significant reduction in the risk of myocardial infarction and cardiovascular death. ICARE Study In 2008, the Israel Cardiovascular Events Reduction with Vitamin E (ICARE) study participants were randomized to Vitamin E (400 IU/day) or placebo for 18 months. The findings showed a statistically significant reduction of 50% in the cardiovascular events in Hp 2-2 diabetic individuals. It was also reported that dual therapy with statins and Vitamin E is superior to statins monotherapy in reducing the risk of cardiovascular disease in individuals with diabetes mellitus and the Hp 2-2 genotype. WAVE Study In this study, a combination of Vitamins E and C was used. On the one hand, Vitamin E treatment improved cholesterol efflux from macrophages and prevented high-density lipoprotein (HDL) oxidation; on the other hand, Vitamin C did not. This study suggested a probability that by combining Vitamin C and E interferes with the shielding effect of Vitamin E on HDL function. Suggested Reading Dalan R, Goh LL, Lim CJ, et al. Impact of vitamin E supplementation on vascular function in haptoglobin genotype stratified diabetes patients (EVAS trial): a randomised controlled trial. Nutr Diabetes. 2020;10:13. Costacou T, Wiener JB, Berinstein EM, Levy AP. Vitamin E, high-density lipoproteins, and vascular protection in diabetes. In: Diabetes-Oxidative Stress and Dietary Antioxidants. 2nd Edition, 2020. pp. 39-406. Han J, Zhao C, Cai J, et al. Comparative efficacy of vitamin supplements on prevention of major cardiovascular disease: systematic review with network meta-analysis. Complement Ther Clin Pract. 2020;39:101142. Craven PA, DeRubertis FR, Kagan VE, et al. Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes. J Am Soc Nephrol. 1997;8(9):1405-14. Goldenstein H, Levy NS, Lipener YT, et al. Patient selection in Vitamin E treatment in diabetes mellitus. Expert Rev Cardiovasc Ther. 2013;11(3):319-26.