Nutrition Notes

Is There a Role for Vitamin A in Reducing Risk for Skin Cancer?

Think about vitamin A and what probably comes to mind first is night blindness. Impaired dark adaptation is one of the earliest signs of vitamin A deficiency, but apart from its role in eyesight, vitamin A has innumerable other functions in the body. It’s essential for healthy skin, proper immune function, reproductive health, regulation of cellular growth, differentiation and gene expression, and healthy pre- and postnatal development. There’s a reason our grandparents had to choke down a spoonful of cod liver oil every day! (Like almost everything in health and nutrition, though, vitamin A has a U-shaped curve. Deficiency can impair fertility and healthy fetal development, but too much vitamin A may be teratogenic.) Zeroing in on vitamin A and the skin, vitamin A and retinoid-containing compounds have long been used to treat various skin conditions, and research from earlier this year suggests that higher vitamin A intakes may be protective against cutaneous squamous cell carcinoma.

This research, published in JAMA Dermatology, was an observational study. It identified an association between higher reported vitamin A intakes and reduced incidence of squamous cell carcinoma (SCC), but it’s critical to note that associations don’t prove cause and effect. Moreover, the association identified here may be somewhat tenuous, because vitamin A intakes were assessed via food frequency questionnaires, which are notoriously unreliable. (If you have trouble remembering what you ate for lunch six days ago, try remembering—accurately—the quantities of certain foods you’ve consumed during the last several years, as well as the frequency.) The validity of food frequency questionnaires and other memory-based recall methods is coming under increased scrutiny. Some researchers have gone so far as to say these types of data are so unreliable that they have “engendered a fictional discourse” on the relationships between dietary elements and various diseases.

Unfortunately, we can’t be certain what the true intake of vitamin A among participants was. Moreover, long-term intake was largely estimated:

“Because dietary intake may prevent skin carcinogenesis during an extended period, we used cumulative means of vitamin A and carotenoid intakes during the follow-up period as a time varying exposure measure to better estimate long-term dietary intake and to minimize within-person variation. For example, intake in 1986 was used for 1986-1990 follow-up, and the mean of 1986 and 1990 intake was used for 1990-1994 follow-up and so on.”

This kind of weakness is not unique to this study. This is a drawback common to all observational and epidemiological research. These endeavors are helpful for identifying associations and for generating hypotheses, but those hypotheses then need to be further tested in clinical trials if possible. Taking this shortcoming into account, we can still potentially learn from the findings.

Data were taken from two large prospective cohort studies: the Nurses’ Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Risk for SCC was determined after adjusting for potential confounders such as hair color, smoking, family history of skin cancer, and the number of severe sunburns they had received during their lifetime. Other important factors were not adjusted for, though, such as avoidance of midday sun.

Participants were divided into quintiles of vitamin A intake. Those in the highest intake quintile reported eating a daily average of the amount of vitamin A equivalents in one medium sweet potato or two large carrots. Intake in the lowest quintile was approximately the equivalent of one small carrot or one-third of a cup of sweet potato—an amount that is still above the current Recommended Dietary Allowance (RDA) for vitamin A. With the lowest intake quintile as the reference point, the pooled multivariate hazard ratios for increasing intake quintiles were 0.97 (95% CI: 0.87-1.07) for quintile 2, 0.97 (0.80-1.17) for quintile 3, 0.93 (0.84-1.03)

for quintile 4, and 0.83 (0.75-0.93) for quintile 5. Similar numbers were seen for lycopene, lutein, and zeaxanthin, even though these carotenoids do not have vitamin A activity.

Taking into account the roles of vitamin A in the immune system, gene expression, and cell differentiation, this nutrient may indeed have a protective role against SCC. But more research will be needed to get closer to establishing cause and effect. For now, this is an intriguing association and perhaps gives patients another reason to make sure they’re getting enough vegetables and fruits—especially the brightly colored yellow, orange, red and green ones. In fact, it’s possible the association between higher estimated vitamin A intake and reduced risk for SCC is not driven by the vitamin A, itself, but by an overall healthy lifestyle. (People who put an emphasis on their health may be more likely to consume nutrient-rich vegetables in place of less wholesome foods. So it could be the vitamin A or any number of other compounds that come along for the ride in these foods or other healthy foods these individuals reported consuming.)

It’s worth taking a quick look at the difference between true vitamin A and its carotenoid precursors. Just as “vitamin E” is an umbrella term for multiple distinct compounds that make up the vitamin E complex, “vitamin A” refers to a host of related compounds called retinoids (retinol, retinal, and retinoic acid). The vitamin A found in animal foods is in the form of retinol, also called preformed vitamin A. It’s a yellow, fat-soluble compound that serves as a precursor to retinoic acid, the most active form of vitamin A in the body. The vitamin A precursors in plant foods are provitamin A carotenoids and they include β-carotene, α-carotene, and β-cryptoxanthin. These can all be converted to retinol in the body, but other commonly consumed carotenoids—such as lycopene, lutein, and zeaxanthin—cannot.

Regarding how to get enough vitamin A, a paper that assessed intake of retinol activity equivalents (RAE) in over a hundred thousand participants from eight different countries concluded that even in the industrialized world, where frank malnutrition is rare, an adequate vitamin A intake cannot be achieved through preformed vitamin A or β-carotene alone, but rather, these must be combined.

Absorption of provitamin A carotenoids and their conversion to vitamin A varies widely among individuals. Absorption of β-carotene from plant foods ranges from 5% to 65% in humans. The bioavailability and vitamin A equivalency of β-carotene are highly variable and are impacted by numerous factors related to the foods themselves, and to the health status of the individual consuming them. These include the food matrix, processing techniques, the concentration of β-carotene, and the amounts of dietary fat, fiber, and preformed vitamin A in the diet, as well as an individual’s vitamin A status, gut integrity, status of other nutrients, and genetic polymorphisms that affect β-carotene metabolism.

Taking these limitations into consideration, β-carotene is still an important contributor to total vitamin A status, especially in vegetarians and strict vegans, and in parts of the world where access to sources of preformed vitamin A is limited. Unlike overdoing preformed vitamin A, high doses of beta-carotene have not been shown to be teratogenic and are unlikely to induce vitamin A toxicity. So, like in much of nutrition, balance appears to be key: some vitamin A from animal foods, augmented by carotenes from plants, with supplementation or inclusion of specific vitamin A-rich foods on an individual basis depending on needs.