Nutritional and lifestyle correlates of the cancer-protective hormone melatonin

Context: Despite growing support for melatonin as a promising agent for cancer treatment and possibly cancer prevention, few studies have elucidated factors that influence endogenous melatonin. This overview summarizes dietary and lifestyle factors that have been shown to affect circulating melatonin levels. Biological mechanisms: To date, many animal studies and in vitro experiments have illustrated that melatonin possesses oncostatic activity. Mechanisms that are currently being studied include melatonin's activity as an indirect antioxidant and free radical scavenger; its action on the immune system; suppression of fatty acid uptake and metabolism; and its ability to increase the degradation of calmoduline and to induce apoptosis. Studies further suggest that melatonin reduces local estrogen synthesis, through down-regulation of the hypothalamic-pituitary reproductive axis and direct actions of melatonin at the tumor cell level, thus behaving as a SERM. Therapeutic applications: Several small clinical trials have demonstrated that melatonin has some potential, either alone or in combination with standard cancer therapy, to yield favorable responses. Melatonin or its precursor tryptophan have been found in numerous edible plants, but more studies are needed to evaluate the influence of diets rich in tryptophan and melatonin on circulating melatonin levels in humans. Age, BMI, parity, and the use of certain drugs remain the factors that have been associated most consistently with aMT6s levels. Discussion: Further insights into the effects of dietary and lifestyle factors that modulate circulating melatonin levels may provide the basis for novel interventions to exploit melatonin for the prevention and treatment of human diseases.