Nutritional and lifestyle correlates of the cancer-protective hormone melatonin

Abstract

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.

Introduction

Melatonin (5-methoxy-N-acetyltryptamine), a derivative of the essential amino acid tryptophan, is an indolamine hormone with levels that vary throughout the day, following a distinct 24-h (“circadian”) rhythm. While produced primarily in the pineal gland, melatonin can also be found in cells of the bone marrow [1], [2] and the gastrointestinal tract [3], [4], [5]. 6-Sulphatoxymelatonin (aMT6s), melatonin's major metabolite, is secreted in urine and, if measured in first morning urine, reflects peak melatonin production from the night before.

Melatonin has been shown to be protective against a variety of cancers in animal models and experimental studies [6]. In the Nurses’ Health Study II (NHS II), higher levels of melatonin were associated with a decreased risk of breast cancer [7]. Observational studies, including those from the two prospective Nurses’ Health Study cohorts, also tend to support this evidence: in both the Nurses’ Health Study (NHS) and NHS II, night work (through light exposure at night, which is associated with lower melatonin levels) has been found to increase both breast as well as colon cancer risk [8], [9], [10]. As trials are under way to study exogenous melatonin's potential in breast cancer prevention, it appears prudent to understand what other factors modify endogenous melatonin levels. Among the factors that have been most consistently linked to melatonin levels to date are age, night work, body mass index (BMI) and parity.

Because humans cannot produce melatonin's precursor tryptophan, it must be part of their diet. Thus, foods high in tryptophan such as milk, meat, poultry (including turkey), fish, sesame seeds, beans, lentils, rice and certain nuts may be associated with variations in melatonin levels. Few studies have explored the influence of nutritional factors on melatonin levels. The aim of this study is to review and summarize dietary and lifestyle factors that have been shown to affect circulating melatonin levels. Data sources were MEDLINE from January 1960 to December 2006, experts in the field, bibliographies, and abstracts. Search terms included melatonin, tryptophan, and lifestyle as well as dietary terms.