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Vitamin E rapidly is becoming a vital link in the prevention and even possibly the reversal of microvascular and macrovascular complications in patients with diabetes. A growing body of research shows that doses in excess of 1,000 IU daily inhibit the inflammatory response, inhibiting monocyte activity and plaque formation, and also prevent retinopathy and nephropathy.
One macrovascular study from the University of Texas (UT) Southwestern Medical Center in Dallas could be the first to show the anti-inflammatory properties of vitamin E at 1,800 IU daily doses.1 A second UT study shows that 1,200 IU dosages daily for people with Type 2 diabetes reduce levels of C-reactive protein (CRP), a predictor for cardiovascular disease.2 And the microvascular study, from Joslin Diabetes Center in Boston, suggests the oxidative effects of vitamin E improve blood flow to the eyes and kidneys with 1,200 IU daily doses.3
The research has potential long-term benefits for patients with diabetes, but it is not yet at the point for clinical recommendations, says George King, MD, Joslin’s acting director of research and supervisor of the microvascular study. In fact, says King, there is no sign anyone is prepared to study the long-term effects of high-dose vitamin E supplementation and clinical practice and its impact on the lives of patients with diabetes. "If vitamin E was a patentable drug, this study would have been done five or 10 years ago," King says. "But since it is not patentable, no one is willing to spend the millions of dollars it would cost for a supplement that costs 25 cents a day."
King does not recommend that patients with diabetes start popping vitamin E like candy, but he says 400 IU to 800 IU daily "won’t hurt, and it may help." Doses higher than 2,000 IU can cause easy bruising and bleeding and are potentially dangerous for patients on warfarin and other thinning agents, says King.
In the first UT Southwestern study on the supplement, researchers compared patients with Type 2 diabetes with healthy controls; 25 patients were randomized to each of three groups and were given 1,200 IU of vitamin E daily for three months, followed by a two-month washout period. Blood was taken from all patients at the beginning of the study, after three months, and again after the washout. The effect of vitamin E was similar in all three groups.
"This is the first study that shows that vitamin E has anti-inflammatory effects in diabetic patients," says Sridevi Devaraj, PhD, assistant professor of pathology at UT and lead author in the study. "This could be a further therapy to prevent vascular complications in diabetes since inflammation seems to be critical as a causative factor in diabetic vascular disease," she adds.
Devaraj found that inflammation caused by white blood cells — monocytes — was significantly reduced with a daily dosage of 1,200 IU of vitamin E, reducing plaque formation on artery walls. The monocyte is crucial and the most readily accessible cell involved in atherogenesis. Study data showed the diabetic monocyte was more active and promoted more inflammation and more free radicals and cytokines, or messenger molecules. The diabetic monocyte also caused more adhesion to lining cells of the artery wall. "It was very important to elucidate the pivotal roles for inflammation in diabetic vascular disease and examine how it could be modulated," says Devaraj.
The second study of 75 subjects found that high intake of the antioxidant vitamin E reduces CRP levels, a predictor of cardiovascular disease. Study participants were divided into three groups:
Each person in each group was given 1,200 IU of natural vitamin E (alpha-tocopherol) daily for three months. Researchers measured each participant’s CRP levels before and after supplementation and after a two-month washout period. They found that vitamin E supplementation lowered CRP levels by 30% in all three groups. Levels of the monocyte interleukin-6, which elicits the secretion of CRP from the liver, decreased an average of 50% in all groups.
"Since this study shows that vitamin E lowers CRP significantly in both diabetics and nondiabetics, it suggests that vitamin E could be an additional therapy in our quest to reduce cardiovascular disease," says Ishwarlal Jialal, MD, PhD, UT professor of pathology and internal medicine and principal investigator in both studies. Jialal's earlier studies have shown that vitamin E is a potent antioxidant.
Blood tests administered before the vitamin E therapy began also showed that diabetic patients, especially those with vascular complications, have increased levels of CRP and interleukin-6. Studies have shown that individuals with and without heart disease and stroke complications are more prone to subsequent heart attacks and stroke if CRP levels are 2 mg/liter or greater.
The Joslin study, published in 1999, looked at 36 patients with Type 1 diabetes and without signs of microvascular complications plus a control group of nine healthy people. They were randomized to 1,800 IU of vitamin E daily or placebo for four months. Before the vitamin E was taken, the baseline blood flow in the retinas of patients with diabetes was 17.3% lower than in the nondiabetic subjects. After four months of 1,800 IU per day of vitamin E, on average, the retinal blood flow of the patients with diabetes returned to 88% of normal. Blood sugar control was unchanged during the study.
"After vitamin E treatment, the blood flow in those patients with diabetes was significantly increased and kidney function appears to be improved as well. The treatment was most beneficial in those cases where blood sugar control was the poorest and the retinal and kidney abnormalities were greatest," says King, who is director of the vascular cell biology section at Joslin and a professor of medicine at Harvard Medical School.
Vitamin E is a low-cost, readily obtainable nutritional supplement with the potential to enhance or even replace more expensive prescription drugs. Vitamin E is found in many common foods, including vegetable oils (soybean, corn, cottonseed, and safflower) and products made from these oils (such as margarine), wheat germ, nuts, and green leafy vegetables.
The recommended daily intake of vitamin E is 60 IU. However, it is very difficult to obtain this amount through normal dietary intake, and nearly impossible to get the high-dose amounts needed to address the micro- and macrovascular benefits that arise in patients with diabetes, says King.
1. Devaraj S, Jialal I. Low-density lipoprotein postsecretory modification, monocyte function and circulating adhesion molecules in Type 2 diabetic patients with and without macrovascular complications: The effect of alpha-tocopherol supplementation. Circulation 2000; 102:191-196.
2. O’Byrne D, Grundy S, Packer L, Devaraj S, et al. Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans. Free Radic Biol Med 2000; 29:834-845.
3. Bursell SE, Clermont AC, King GL, et al. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with Type 1 diabetes. Diabetes Care 1999; 22:1,245-1,251. www.nhlbi.nih.gov/guidelines/obesity/practgde.htm.