~ 030708 Alpha and Gamma-Tocopherol Reduce Oxidative Stress And Inflammation Markers In Metabolic Syndrome Patients

The March 15, 2008 issue of Free Radical Biology and Medicine published the results of a study conducted by investigators at the University of California Davis Medical Center in collaboration with researchers at the Linus Pauling Institute who report that supplementing with alpha and gamma-tocopherol reduced oxidative stress and inflammation in men and women with metabolic syndrome. Gamma-tocopherol is one of eight forms of vitamin E, which include four tocopherols and four tocotrienols. Alpha-tocopherol has been considered to be the main form of vitamin E for a number of years; however, research continues to confirm the importance of gamma and other tocopherols in human health.

Eighty men and women who had at least three metabolic syndrome features, which include increased waist circumference, elevated triglycerides, hypertension, elevated fasting blood sugar and low high density lipoprotein cholesterol, participated in the current study. The subjects were divided to receive 800 milligrams alpha-tocopherol, 800 milligrams gamma-tocopherol, 800 mg alpha plus 800 milligrams gamma-tocopherol, or a placebo daily for six weeks. Blood samples collected upon enrollment and at the end of the study were analyzed for inflammatory cytokines (interleukin-1b, tumor necrosis factor-alpha, interleukin 6), C-reactive protein (a marker of inflammation), oxidative stress biomarkers, and other factors. Urine samples were tested for nitrotyrosine, a marker for protein modification by nitric oxide-derived oxidants, which may be an inflammatory mediator in heart disease. Alpha and gamma-tocopherol and levels of their metabolites were measured in plasma and urine.

In the group that received alpha-tocopherol alone, plasma levels of the vitamin increased by the end of the study, while, significantly, gamma-tocopherol levels declined by 37 percent. Gamma-tocopherol levels doubled in those that received gamma-tocopherol alone, and increased to a smaller extent in the alpha-gamma combination group.

Although alpha-tocopherol, gamma-tocopherol and both tocopherols taken together reduced C-reactive protein, only the combination group experienced a significant reduction compared with the placebo group. The combination group as well as those who received only alpha-tocopherol experienced a reduction in tumor necrosis factor-alpha. All groups receiving tocopherols experienced a decrease in oxidative stress biomarkers. Urinary nitrotyrosine levels declined among those who received gamma or both tocopherols, but not in those receiving alpha-tocopherol alone.

"The combination of alpha-tocopherol and gamma-tocopherol supplementation appears to be superior to either supplementation alone on biomarkers of oxidative stress and inflammation and needs to be tested in prospective clinical trials to elucidate its utility in cardiovascular disease prevention," the authors conclude.

Related Health Concern: Chronic inflammation

Chronic inflammation is also involved in diseases as diverse as atherosclerosis, cancer, heart valve dysfunction, obesity, diabetes, congestive heart failure, digestive system diseases, and Alzheimer's disease (Brouqui et al. 1994; Devaux et al. 1997; De Keyser et al. 1998). In aged people with multiple degenerative diseases, the inflammatory marker, C-reactive protein, is often sharply elevated, indicating the presence of an underlying inflammatory disorder (Invitti 2002; Lee et al. 2002; Santoro et al. 2002; Sitzer et al. 2002). When a cytokine blood profile is conducted on people in a weakened condition, an excess level of one or more of the inflammatory cytokines, e.g., TNF-a, IL-6, IL-1(b), or IL-8, is usually found (Santoro et al. 2002).

In a study published in the July 18, 2001 issue of the Journal of the American Medical Association, a group from the famous Women's Health Study was evaluated to ascertain what risk factors could predict future development of Type II diabetes (Pradhan et al. 2001). The findings showed that baseline levels of C-reactive protein and interleukin-6 (IL-6) were significantly higher among those who subsequently developed diabetes compared to those who did not.

When comparing the highest versus lowest quartile, women with the higher IL-6 levels were 7.5 times more likely to develop diabetes while those in the higher C-reactive protein ranges were 15.7 times more likely to become diabetic. After adjusting for all other known risk factors, women with the highest IL-6 levels were 2.3 times at greater risk, while those with the highest C-reactive protein levels were 4.2 times more likely to become diabetic. It should be noted that these other diabetic risk factors (such as obesity, estrogen replacement therapy and smoking) all sharply increase inflammatory markers in the blood.
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