Vitamin C (ascorbic acid or its ascorbate salt) has some redeeming activities, but it can uncouple down-regulation of HMG-CoA Reductase by monooxygenase-catalyzed reactions, thereby increasing the potential for oncogenic expression and tumor growth. A preliminary probe with mice receiving 4 mg vitamin C/day/kg (the human equivalent of 280 mg/day) produced a slight, but probably insignificant increase in melanoma growth, raising serious doubts as to whether or not megadoses of vitamin C (more than half a gram) should be advocated for melanoma patients. High doses of vitamin C also can increase exposures to the autoxidation by-product, dehyroascorbic acid, which is reported to be diabetogenic. Because of these complications, other, more effective antioxidants, such as melatonin and/or vitamin E may be better choices for controlling the pathology of unregulated oxidative processes.
Ethoxyquin is a preservative used in human and animal foods to prevent fats from oxidizing and becoming rancid. Ethoxyquin has also been used as a herbicide suggesting an alternate route into our food chain. Its use in tires raises concerns that inhalation of dust from the wearing away of millions of tires might be a predisposing factor in lung cancer? Material Safety Data Sheets list ethoxyquin as a liver toxin, and there are reports in the literature linking topical exposures to contact dermatitis. Ethoxyquin and vitamin C reportedly can promote the growth of some tumors in laboratory animals.
Ethoxyquin bears an uncanny chemical and structural resemblance to melatonin, the main difference being a ring structure that is only one carbon larger. Ethoxyquin can probably bind to a receptor for melatonin but its "size and shape" could prevent it from functioning like the natural hormone and might cause an inhibition of melatonin's production and function. Though usually quite effective, it is interesting to note that the vitaletheine modulators have seldom produced long-term therapeutic benefits in animals maintained on ethoxyquin-containing diets.
Other non-nutritive antioxidants, such as BHA and BHT, are of concern for their estrogenic activities and for their dramatic effects upon prostaglandins, potent hormonal substances produced from arachidonic acid that control artery and smooth muscle contractions and the dilation of veins. This estrogenic activity may be particular problematic for women already suffering from the effects of the estrogen, diethylstilbesterol, administered to their mothers to allegedly prevent spontaneous abortions. Of the "natural antioxidants", vitamin E has some of the more interesting effects upon the monooxygenase activity and upon AIDS models. Effects of melatonin upon these systems are currently being investigated.
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