Investigations on hypervitaminosis E in rats

In view of the fact that some fat soluble vitamins are toxic in large doses to experimental animals and man, this study was initiated to investigate the long-term effects of low, moderate and high levels of dietary vitamin E on various metabolic parameters in the rat. Six groups of female Wistar rats (50 g) were fed for as long as 16 months the basal vitamin E-free diet with supplements ranging from 0 to 25»000 IU vitamin E (DL-a-tocopheryl acetate) per kilogram diet. The levels of vitamin E chosen were 0, 25, 250, 2,500, 10,000 and 25,000 IU/kg diet; 0 representing vitamin E-free, 25 representing moderate level and 250 to 25»000 representing large doses. All nutrients in the basal diet except vitamin E were adequate. The focus of this study was on the effects of large doses of dietary vitamin E on: (l) the hematological indices such as hematocrit and hemoglobin levels, prothrombin time and erythrocyte hemolysis at 9, 12 and 16 months of treatment; (2) urinary creatine and creatinine levels at 11 months of treatment; (3) body weight and various organ weights at 8 and 16 months of treatment; (4) femoral parameters such as ash content, and calcium and phosphate concentrations of bone at 8 and 16 months of treatment; and (5) the levels of a-tocopherol, vitamin A, total lipids, and cholesterol in liver and plasma at 8 and 16 months of treatment. Rats fed 10,000 and 25.000 IU vitamin E/kg diet for 8 and 16 months had significantly reduced body weights in comparison to those receiving the moderate level of vitamin E. The depressing effect of excess dietary vitamin E on body weight was not as marked as that of vitamin E deficiency. There was little difference between the moderate and high vitamin E supplemented groups with respect to the weights of liver, uterus and kidney. However, high levels of dietary vitamin E increased the relative heart weights after 8 months and the spleen weights after 16 months. Hemoglobin and hematocrit values were not influenced by excessive amounts of vitamin E after 9 or 12 months of treatment. At 16 months however, the hematocrit values of rats fed 10,000 and 25,000 IU vitamin E/kg diet were increased significantly over those of rats fed 25 IU/kg diet. The prothrombin time was reduced in rats treated with excess dietary vitamin E for 12 and 16 months. Only vitamin E deficiency, but not excess vitamin E, was associated with increased membrane fragility of erythrocytes. In rats subjected to excess vitamin E for 16 months the ash content of bone was decreased. High levels of dietary vitamin E increased the plasma alkaline phosphatase activity after 16 months of treatment. These results indicate that there may be increased mineral turnover in bones of rats fed high levels of vitamin E for prolonged periods. Urinary levels of creatine and creatinine were not affected by high levels of dietary vitamin E. However, in the vitamin E deficient rats, the creatine excretion increased while the creatinine excretion decreased, resulting in a very high ratio of creatine/creatinine in urine. The α-tocopherol stored in liver rose significantly with increasing dietary vitamin E. A logarithmic relation was demonstrated between liver α-tocopherol concentration and dietary levels of vitamin E. The total α-tocopherol in whole liver of rats fed the different levels of vitamin E for 16 months was approximately double that in rats treated for 8 months. A curvilinear relationship between plasma tocopherol and the logarithm of dietary vitamin E was found in rats treated for 8 and 16 months. Total lipids in liver increased significantly with increasing dietary vitamin E in rats treated for 8 months, but not in rats treated for 16 months. There was little difference in liver cholesterol concentration between the moderately supplemented and highly supplemented groups. Increasing dietary vitamin E significantly lowered plasma total lipids and cholesterol in rats treated for 16 months. A quantitative examination of the data showed that the reduction in plasma total lipids was not simply a reflection of the cholesterol levels, and suggests that a high dietary level of vitamin E affected one or more of the constituents of the total lipids (phospholipids and/or triglycerides) other than cholesterol. From the findings of this long-term study, it appears that high levels of dietary vitamin E result in biochemical changes in some aspects of metabolism in rats. Some of the changes worth recognition are the depression in body weight, increase in relative spleen and heart weights, decrease in ash content of bones with concurrent increase in plasma alkaline phosphatase activity, increased hematocrit value and fatty liver in rats treated for 8 months. A logarithmic relationship was observed between dietary levels of vitamin E and the concentrations of this vitamin in liver and plasma. The results of this study suggest that excess vitamin E over prolonged periods of time have some harmful effects in rats.Land and Food Systems, Faculty ofGraduat