Long-term effects of chromium, grape seed extract, and zinc on various metabolic parameters of rats.

Progressive insulin resistance may contribute to both enhanced glycosylation of proteins and nucleic acids and augmented free radical damage commonly associated with aging. Accordingly, ingestion of chromium and antioxidants which improve insulin sensitivity and/or lessen free radical formation could theoretically ameliorate these basic disorders and lessen signs and symptoms of chronic age-related disorders. However, this supposition is based primarily upon acute rather than chronic data. Therefore, we divided 104 F344/BN rats into 2 groups: a control group receiving a basic diet and a test group receiving the same diet with added chromium polynicotinate (5 ppm), zinc monomethionine (18 ppm elemental zinc), and a grape seed extract high in flavonoids (250 ppm). Initial mean systolic blood pressures (SBP) of both control and test groups were 122 mm Hg. Over the first 7 months, the SBP of the control animals steadily increased to 140 mm Hg and remained at this level for the next 7-8 months. In contrast, the SBP of the test animals initially decreased over the first 4 months to as low as 110-114 mm Hg. The SBP then increased over the following months, essentially reaching the starting value of 120 mm Hg. This was still significantly lower than control (p < 0.001). In 12 control and 12 test rats, hepatic TBARS formation, an estimate of lipid peroxidation/free radical formation, was significantly lower after 1 year ingesting the test diet (p < 0.04); and HbA1C was also statistically significantly lower in the test group (5.4 vs. 4.8%, p < 0.003). Circulating levels of cholesterol, HDL, and triglycerides were similar between the two groups. Body, kidney, and liver weights were not different after 1 year ingesting the different diets; but epididymal fat pad weight was less in the group receiving supplements. We conclude that after prolonged supplementation a combination of agents known to sensitize insulin response and act as antioxidants (chromium polynicotinate, grape seed extract, and zinc monomethionine) can markedly lower SBP in normotensive rats, lessen oxidative damage to fats as suggested by decreased TBARS formation, and lower HbA1C without showing signs of toxicity.