Evidence-Based Nutritional Chemoprevention of Melanoma
Can nutritional supplements prevent melanoma? Interest in the role of nutrition in health dates back at least two and one-half millennia, and many Hippocratic writings emphasize the role of diet. Historically, Scurvy was the scourge of long ocean voyagers, and arctic explorers who ate polar bear liver suffered symptoms of Vitamin A intoxication. Nutritional deficiency studies in rats, emphasizing the morphological and biochemical changes in skin, were common in the first two decades of the JID (1940-1950s).
We now know the molecular basis of the action of most vitamins, and we understand the nuclear receptors of fat soluble vitamins (A and D) and their effects on gene transcription, so the time is ripe for looking at the evidence for and against vitamins’ influence on disease.
The effect of Vitamin A and carotenoids (dietary and in pills from bottles) on the incidence of melanoma is actively being studied. Conducting such epidemiological studies is an arduous endeavor, requiring active participant involvement, significant funding, and the understanding that rats and molecules are not people. The ‘holy of holies’ -- the randomized controlled trial -- is difficult to perform in long-term nutritional studies. Parts of the VITAL (VITamin And Lifestyle) study include 69,635 individuals (approximately 94% white) from western Washington (including Seattle) who are being followed with respect to nutritional assessment and melanoma incidence (as well as other diseases). The population is relatively well-educated (86% “some college”); participants reported high levels of multivitamin and other supplement use, and 27% reported NSAID use. Older individuals reported less supplement use. There were not enough participants to allow all the subgroup analysis that might be desired, a challenge even in relatively large epidemiological studies.
In a recent JID article, Asgari and colleagues report 566 melanomas (256 in situ and 309 invasive) developed in this population over an average of 5.84 years of follow-up. Agonizingly detailed prospective nutritional histories as well as vitamin and mineral supplement histories are maintained for this cohort. The reliability of the questionnaires was ascertained by repeated testing and detailed nutritional interviews, and validation was tested by comparing the results of nutritional questionnaires with blood levels of various minerals and nutrients, including beta-carotene. The investigators calculated retinol and carotenoid levels from the nutritional data and stratified them. The statistical models they used corrected for the multiple variables in the study.
Yes, exact daily levels of intake and blood and tissue levels of the nutrients might make the study better, but the perfect should not be the enemy of the doable. This is evidence-based nutritional medicine in the real world. Beta-carotene, one of 563 dietary carotenoids, has less than a 10% conversion rate to pro-vitamin A, and some common carotenoids such as lutein, lycopene and zeaxanthin are not precursors of vitamin A at all. In the data presented, carotenoids – whether dietary or in the form of supplements -- had no effect on melanoma incidence.
By contrast, increased Retinol levels from supplements were associated with reduced levels of melanoma. Current use of supplements was an important variable, but not past use of supplements. Interestingly, this effect was more prominent in melanomas on sun-exposed areas. The reduction in melanoma incidence in women was responsible for the overall reported melanoma risk reduction.
SO: What to tell the next person who asks about Vitamin A supplementation to prevent melanoma?
Diet per se is not effective in reducing melanoma, and dietary or supplemental carotenoids do not seem to have a protective effect against the disease. The data suggests that some individuals are benefited, as measured by dietary histories, by supplemental retinoids. Whether the increased levels of vitamin A have deleterious health effects is not clear. Since DNA was collected on some of the VITAL patients, eventually it may be possible to identify subgroups of patients at varying risks for melanoma (and, thereby, subgroups of patients who may benefit more from retinoid supplements).
We would be especially interested in comments from those with experience with large preventive studies, the role of nutrition in skin diseases, and issues issues related to melanoma studies that may confound preventive studies. What other thoughts does this article provoke? Let’s hear from you.
Credit: This image is by Identity Photogr@phy and it is used via a Creative Commons License; the original can be found on Flickr.