Melanoma, the uncontrolled growth of pigment-producing cells, is the most serious form of skin cancer and is expected to afflict an estimated 122,000 men and women in the U.S. in 2009, according to the American Academy of Dermatology. Two years ago, the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study (Journal of Nutrition 137:2098-2105, Sept. 2007) reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants. However, a new study from researchers at Kaiser Permanente in Oakland, CA, took the SUVIMAX study to task, refuting its results and reassuring consumers that taking vitamins will not increase their chances of developing melanoma.

The 2007 SUVIMAX study tested the efficacy of antioxidants in reducing the cancer incidence in the general population and found that oral daily supplementation with a combination of antioxidants—120 mg of vitamin C, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium and 20 mg of zinc—over the course of 7.5 years increased the incidence of melanoma in women by 4%. The study results prompted the researchers to conclude that their results suggested that “regular intake of such nutrients may be associated with harmful effects.”

Kaiser Permanente researchers sought to confirm these findings by examining melanoma incidence in their Vitamins and Lifestyle (VITAL) study, a 2-year-long population-based prospective cohort study that examined a total of 69,671 men and women from western Washington state, aged 50-76. The participants answered a lengthy questionnaire about their lifestyle, health history, diet, supplement use, personal characteristics and cancer risk factors in spanning the past decade. About 66% of the participants were either current or past users of multivitamins.

Researchers paid particular attention to the self-reported use of the five supplements used in the SUVIMAX trial—vitamin C, vitamin E, beta carotene, selenium and zinc—in the 10 years before baseline. The doses of vitamin C, vitamin E and zinc supplements used in the SUVIMAX study corresponded to the amounts found in a standard multivitamin. In the SUVIMAX study, the beta carotene and selenium doses were several times greater than those in a standard multivitamin, prompting researchers to conduct further analyses on the supplemental use of those two nutrients.

In the end, the researchers did not detect a significant connection between multivitamin use and melanoma risk in women or in men. They also did not observe increased melanoma risk with the use of supplemental beta carotene at doses comparable with those of the SUVIMAX study. Their complete findings were published in the Archives of Dermatology (Vol. 145 (No. 8), Aug. 2009).

Points of Conjecture

In addition to their vitamin research, the Kaiser Permanente team also speculated on where the SUVIMAX study went wrong, writing that its results could be attributed to “methodological shortcomings.”

“Their analysis,” they wrote, “was limited to a subsample of participants who agreed to answer a single question on their lifetime sun exposure (‘How would you describe the intensity of your skin’s exposure to the sun during your lifetime?’), which could introduce selection bias and limit generalizability. Also, the response to that question, which was the only melanoma risk factor ascertained other than age, current smoking status and latitude of residence, was excluded from their multivariable analysis.”

The study also identified few incident melanomas, they said, possibly “owing to inaccurate case ascertainment, which may explain the 5-fold lower rates of incident melanomas in the SUVIMAX trial (25 cases per 100,000 person-years) compared with the VITAL study (120 cases per 100,000 person-years).”

They also cited several limitations in the SUVIMAX study, including the absence of detailed information on some known melanoma risk factors, such as sunlight exposure at early ages and number of birthmarks, moles or any other kind of skin growths (nevi) the participant might have had.

With regard to antioxidant supplement usage, Kaiser Permanente researchers also pointed to SUVIMAX’s lack of physiologic measures (such as serum levels) of such usage, relying instead on self-reported use data. “In summary,” they wrote, “these data suggest no association between self-reported multivitamin use and supplemental selenium and beta carotene use similar to doses used in the SUVIMAX study and melanoma risk.”

They concluded by advising that the results of the SUVIMAX study “should be interpreted with caution.”

Lead study author, Maryam Asgari, MD, MPH, dermatologist and research scientist, Kaiser Permanente, said she was inspired to convene this study because she was worried the results of the SUVIMAX trail were misleading. “I was concerned about the results of the SUVIMAX trial suggesting that women who were taking nutritionally appropriate doses of certain supplements were at increased risk of melanoma,” she said, noting that at present she is not planning additional research in this area of study.

“Because an estimated 48% to 55% of U.S. adults use vitamin or mineral supplements regularly, it’s important for consumers to know that our study did not replicate the findings from the SUVIMAX study,” concluded Dr. Asgari. “No one study can tell the whole story, so it’s important for scientists and consumers alike to consider the entire evidence base.”