Diabetic subgroup may benefit from vitamin E.
CHICAGO -- Evidence continues to build that vitamin E, an antioxidant supplement that became discredited and discarded for preventing cardiovascular disease events through the accumulated results from several large, negative trials, may actually have a substantial benefit for a select subgroup of patients with diabetes.
The key appears to be targeting vitamin E to patients with diabetes who also have a haptoglobin 2-2 genotype, which means they lack a robust antioxidant effect from this blood protein. Roughly a third of people in Western populations carry this genotype. Everyone else has a 1-1 or 2-1 genotype, both of which produce haptoglobin with adequate antioxidant activity.
The latest results to back up this paradigm came from a post hoc analysis of the 1,027 women with diabetes enrolled in the Women's Health Study (WHS). In this analysis, women with diabetes and the haptoglobin 2-2 genotype who received an every other-day supplement of 600 IU of vitamin E had a 15% reduced rate of cardiovascular disease events during an average 10 years of follow-up compared with similar women randomized to placebo, Dr. Shany Blum said at the meeting.
In contrast, post hoc analysis of WHS women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of cardiovascular disease events during follow-up compared with similar women who received placebo.
The stroke rate in women with the 2-1 haptoglobin genotype was 5.7% in those who received vitamin E and 1.2% in the placebo arm, a 4.5-fold increased rate of stroke after adjustment, said Dr. Blum, a researcher at the Technion-Israel Institute of Technology in Haifa.
These findings follow similar observations about the interaction of vitamin E and the haptoglobin genotype in both women and men with diabetes in a post hoc analysis of data from the Heart Outcomes Prevention Evaluation (HOPE) study (N. Engl. J. Med. 2000;342:154-60), and from a prospective test of vitamin E compared with placebo in 1,434 patients with diabetes and the haptoglobin 2-2 genotype in the Israel Cardiovascular Events Reduction With Vitamin E (ICARE) study (Arterioscler. Thromb. Vasc. Biol. 2008;28:341-7).
Both studies used a daily supplement with 400 IU of vitamin E. The Haifa researchers published a metaanalysis of the results from HOPE and ICARE in patients with diabetes analyzed by their haptoglobin genotype last May (Pharmacogenomics 2010; 11:675-84).
"We have now addressed, in three independent studies, the ability to target specifically haptoglobin 2-2 individuals with antioxidant treatment, particularly vitamin E," said Dr. Andrew R Levy, professor of anatomy and cell biology at the Technion-Israel Institute and the lead investigator of these analyses and the ICARE study.
"We've now shown in the HOPE study, ICARE, and WHS that patients with the 2-2 genotype [and diabetes] benefited from receiving vitamin E. In HOPE, they had about a 30% reduction in cardiovascular events [compared with patients who received placebo], in ICARE about a 45% reduction in cardiovascular events, and in the WHS about a 15% reduction in cardiovascular events," Dr. Levy said in an interview.
The HOPE and WHS studies "had previously both shown no overall benefit from vitamin E" compared with placebo when the analysis included all participants, regardless of their diabetes status and haptoglobin genotype status. "But when we specifically targeted people with 2-2, they benefited from vitamin E treatment," he said.
Dr. Levy stressed that in his opinion this paradigm needs additional testing in a large, prospective trial before physicians start routinely prescribing vitamin E to patients with diabetes and a haptoglobin 2-2 genotype. He conceded, however, that such a study may be difficult to fund, as no drug company stands to reap a financial benefit from vitamin E, an inexpensive generic agent.
At least one expert familiar with this work believes the evidence that Dr. Levy and his associates have collected warrants starting vitamin E supplementation immediately in informed and willing patients who have the right risk profile.
A daily dose of 400 IU of vitamin E is "cheap and innocuous," commented Dr. Eliot A. Brinton, director of the metabolism section in the cardiovascular genetics division at the University of Utah, Salt Lake City. "The question that I would pose to my patients with diabetes is 'Do you want this?' Many of my patients would probably say yes, they do."
Major Finding: Among women with diabetes who had the haptoglobin 2-2 genotype, every-other-day supplementation with 600 IU of vitamin E led to a 15% reduction in all cardiovascular events during 10 years of follow-up and a 4.5-fold reduction in stroke compared with similar women who were randomized to placebo.
Data Source: Post hoc analysis of 1,027 women with diabetes who were enrolled in the Women's Health Study.
Disclosures: Dr. Blum said he had no disclosures. Dr Levy has served as a consultant for Synvista Therapeutics. Dr. Brinton said that he has served as a consultant to. or as a speaker for, Abbott, Amarin. AstraZeneca. Atherotech, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline Kaneka, Kowa, Kronos Longevity Research Institute, Merck, and Takeda. He has received research grants from Abbott, the Aurora Foundation, and GlaxoSmithKline, and has been an expert witness for the law firm of Reilly Pozner.
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|Title Annotation:||METABOLIC DISORDERS|
|Author:||Zoler, Mitchel L.|
|Publication:||Family Practice News|
|Date:||Feb 1, 2011|
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