ABSTRACT
High doses of vitamin E close to the upper limit of toxicity (UL) but still recommended and considered as harmless and beneficial, can possibly cause a number of adverse effects. In a 14-day study, in which male mice were exposed to intra peritoneal doses of 100 and 200 mg vitamin E (alpha-tocopherol)/kg bw/day, biomarkers of oxidative stress related processes (ROM, TTL), and biomakers of tissue toxicity (ALP, ALT, AST, LDH) and inflammation (MCP-1, IL-6, TNF-α, PAI-1 and resistin) were determined. Oxidative stress parameters in plasma did not change, whereas some biomarkers of inflammation were statistically significantly higher on exposure to vitamin E. In the liver, beneficial effects on tissue biomarkers were observed, whereas the inflammation biomarkers showed an U-shaped relation with the dose of vitamin E. In the kidney, the biomarkers of tissue damage showed mixed effects, whereas a substantial increase in the inflammation biomarkers was observed. In the brain, the biomarkers of tissue toxicity showed beneficial effects, whereas the inflammatory biomarkers showed an increase or an U-shaped behaviour with increasing doses of vitamin E. Especially, a dose of 200 mg of vitamin E/kg bw/day showed a number of adverse effects in several tissues. These results confirm our previous study in male mice with exposure of vitamin E by feed. Since the dose of 200 mg of vitamin E/kg bw/day is lower than the upper limit for vitamin E, the UL should be re-evaluated, in view of the effects in kidney and brain.
ABSTRACT
The benefits of multi-vitamin and mineral supplements in the (elderly) population are questioned and even adverse side effects have been reported. In the present study, the potential adverse effects of a low-dose of multivitamin and minerals is examined by a biomarker approach in young and old human volunteers. A low dose of vitamins and minerals being 100% of the recommended daily intake (RDI) of each vitamin and 18-150% of the RDI of minerals was given for one month and 2 times this dose for another month. The renal toxicity was monitored by measurement of serum of creatinine, urea and uric acid. Changes in renal biomarkers were not observed in each of the groups. Hepatotoxicity was followed by the enzymes alanine aminotransferase and aspartate aminotransferase, albumin, total cholesterol and bilirubin. The activity of alanine aminotransferase statistically significantly increased in both women groups only. In the young group, the activities increased from 15.2 IU/L to 18.1 IU/L (P = 0.102). In the older women group, the activity increased from 19.0 to 20.9 IU/L (P = 0.017). The increase in the activity of aspartate aminotransferase occurred in the two women groups as well, but the increase was only statistically significant in the older women group with a mean increase from 20.5 to 23.4 IU/L (P = 0.013). In 16% of the women, the enzyme activities were above the upper threshold value of the clinical reference range after supplementation. This finding supports the recommendation to perform more toxicity studies on supplements before marketing.
ABSTRACT
A food consumption survey in the Dutch elderly population (51-69 years of age) showed an increased trend in micronutrient supplement intake (36.4%; 120/347 participants). Because data on chemical sensitivity in the elderly is lacking, evaluation as to whether the current uncertainty factor (UF) of 10 is sufficient to protect the elderly was investigated using the micronutrient consumption data in the elderly Dutch population as a case study. Theories of ageing, and differences in toxicokinetic and toxicodynamics are briefly discussed in the context of chemical sensitivity in the elderly. Evidence suggests that for the healthy elderly, no additional default UFs are recommended because the present UF of 10 is probably sufficient. However, more research is needed to ensure that there is no additional risk, particularly in the not-so healthy elderly population. Although there is a trend of increased consumption of micronutrient supplements (i.e. vitamins and minerals) by the Dutch population, the existing European legislation for micronutrients in fortified foods (Regulation 1925/2006) and food supplements (Directive 2002/46) is now being translated to simultaneously set maximum levels of micronutrients in foods and in supplements. For the healthy elderly, no foreseeable risk is expected due to the consumption of micronutrients. For the unhealthy elderly, the effects of micronutrient consumption are not yet known and therefore, dietary supplement intakes need to be continuously monitored with detailed questioning on health status, supplement and prescription drug use. In addition, the generation of an international and up-todate database on the composition of available dietary supplements is needed to fill the current data gaps.