MADRID—Individuals with type 2 diabetes and hypertension are best advised to avoid taking supplemental vitamin E, especially if they’re on pressure-lowering drugs.
Data from an Australian study indicate that compared with a soy oil placebo, mixed tocopherols and RRR-d-alpha tocopherol, the two most common supplemental forms of vitamin E, can increase mean daytime and nighttime blood pressures. Dr. Ian B. Puddey, of the Department of Medicine, University of Western Australia, Perth, presented the surprising findings at the 16th Annual European Meeting on Hypertension.
The vitamin E did reduce oxidative stress, evidenced by consistent falls in urinary f-2-isoprostane (a marker of oxidative stress) among the treated patients. But this beneficial effect is outweighed by the observed hypertensive effect of the vitamin. The Australian investigators saw increases in both systolic and diastolic pressures, as well as pulse pressure, and pulse rate in the vitamin E treated patients. Dr. Puddey said these findings were unexpected and quite surprising.
The observations emerged out of a trial in which the investigators randomized 55 patients with type 2 diabetes and hypertension to treatment with either a placebo (soy oil stripped of all tocopherols), 500 mg per day of mixed gamma, alpha and delta tocopherols, or 500 mg of RRR-alpha tocopherol. They used 24-hour ambulatory monitors to track blood pressure changes throughout the day and night. Many of the patients were also taking at least one antihypertensive drug, and two-thirds were on statins or other lipid-lowering drugs.
Dr. Puddey said the experiment was designed around a hypothesis that vitamin E would actually lower blood pressure; the investigators expected to see higher mean pressures among the placebo treated people. This was not the case.
They actually saw a small decline in blood pressure in the placebo group, but increased mean pressures in both the alpha-tocopherol and mixed tocopherol groups. The mean increase was 7 mmHg systolic and 5 mmHg diastolic for the vitamin E treated patients. The pressure increases were sustained and consistent throughout the 24-hour monitoring periods, showing no diurnal variation.
Though the clinical significance is unclear, they also observed a small increase in mean heart rate of 2 beats per minute in the subjects taking the vitamin E.
These findings are very surprising given that prior animal studies showed marked reduction in blood pressure among stroke-prone rats treated with vitamin E at doses equivalent to human doses of 120 IU per day. Dr. Puddey added that there is only one other human study of vitamin E’s impact on blood pressure in diabetic individuals. It showed a non-significant increase in systolic pressure and an impairment of endothelial function.
Dr. Puddey believes the current findings carry an important clinical message: that vitamin E is not always a benign substance, and diabetic people with hypertension need to be extremely careful with it.
He and his colleagues have no obvious explanation for observed pressure increases. He noted, however, that the various forms of vitamin E are metabolized by hepatic cytochrome P450 enzymes, the same enzymes that process many commonly used cardiovascular drugs. So one possible explanation is that the vitamin interfered with the metabolism of the various drugs the patients were taking, leading to a loss of pressure control. This speculation remains to be evaluated in future studies.
Vitamin E has been taking it on the chin in recent years, as a number of studies have shown that it does not have the cardioprotective effects it was presumed to have. Critics have contended that most of these trials have exclusively used alpha-tocopherol, only one of the 8 tocopherols and tocotrienols found in natural food sources of vitamin E. That argument is harder to uphold in the case of this Australian trial, since the investigators used mixed tocopherols as well as alpha-tocopherol.
Dr. Puddey believes that a vitamin E–induced increase in blood pressure may be an important factor underlying the findings of a recent metanalysis by Miller et al. (Ann Int Med. 2005) showing that vitamin E at doses of 500–2,000 IU per day increased overall mortality rates, a finding which shocked many in the nutritional medicine field.
Though it is clear that people with diabetes and hypertension should avoid taking large doses of vitamin E, Dr. Puddey stressed that these findings should not be extrapolated to vilify the vitamin in general. There is not yet any evidence that vitamin E produces blood pressure increases in either non-diabetic hypertensive individuals, or the general population.
