Higher vitamin A intake linked to lower skin cancer risk

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VitaminAPeople whose diets included high levels of vitamin A had a 17% reduction in risk for getting cutaneous squamous cell carcinoma, the second-most-common type of skin cancer, as compared to those who ate modest amounts of foods and supplements rich in vitamin A. That’s according to researchers from Brown University, who unearthed that finding after analysing data from two long-term observational studies.

Cutaneous squamous cell carcinoma is the second-most-common type of skin cancer among people with fair skin. Vitamin A is known to be essential for the healthy growth and maturation of skin cells, but prior studies on its effectiveness in reducing skin cancer risk have been mixed, said Eunyoung Cho, an associate professor of dermatology and epidemiology at Brown.

“Our study provides another reason to eat lots of fruits and vegetables as part of a healthy diet,” said Cho, who is also an associate epidemiologist at Brigham and Womens Hospital. “Skin cancer, including squamous cell carcinoma, is hard to prevent, but this study suggests that eating a healthy diet rich in vitamin A may be a way to reduce your risk, in addition to wearing sunscreen and reducing sun exposure.”

The research team led by Cho looked at the diet and skin cancer results of participants in two large, long-term observational studies: the Nurses Health Study, which followed 121,700 US women from 1984 to 2012, and the Health Professionals Follow-Up Study, which followed 51,529 US men from 1986 to 2012.

Between the two studies, some 123,000 participants were white (and thus had significant risk of developing skin cancer), had no prior history of cancer and completed the dietary reports multiple times. Among these individuals included in the team’s subsequent analysis, a total of 3,978 cases of squamous cell carcinoma were reported and verified within the 24- or 26-year follow-up periods.

Both studies also asked the participants about hair colour, the number of severe sunburns they had received in their lifetime and any family history of skin cancer, and the researchers adjusted for these and other factors. The studies did not, however, ask participants about their avoidance of mid-day sun, known to be a major risk factor for skin cancer.

After grouping the study participants into five categories by vitamin A intake levels, the researchers found that people in the category with the highest average daily total vitamin A intake were 17% less likely to get skin cancer than those in the category with the lowest total vitamin A intake.

Those in the highest category reported eating on average the amount of vitamin A equivalent to one medium baked sweet potato or two large carrots each day. Those in the lowest category reported eating a daily average amount of vitamin A equivalent to one-third cup of sweet potato fries or one small carrot, which is still above the US Recommended Dietary Allowance of vitamin A.

The team also found that the majority of vitamin A came from the participants’ diets, particularly from fruits and vegetables, rather than from animal-based foods or vitamin supplements. Plant-based sources of vitamin A include not only sweet potatoes and carrots, but leafy green vegetables and fruits like apricots and cantaloupe. Milk, some types of fish and liver are rich sources of animal-based vitamin A.

Cho cautioned that too much vitamin A, particularly from supplements and animal sources, can lead to nausea, liver toxicity, increased risk of osteoporosis and hip fracture, and even birth defects. Side effects from high levels of plant-based vitamin A are minimal, she added.

The researchers also found that eating high levels of other plant-based pigments similar to vitamin A – such as lycopene, commonly found in tomatoes and watermelon – was associated with decreased risk of skin cancer.

Because the analysis was based on studies surveying a large number of people about the foods they ate and observing whether or not they got skin cancer, rather than a randomised clinical trial, it cannot establish cause and effect. It’s possible that another factor may have led to the differences – such as the fact that people who consumed more vitamin A also tended to drink less alcohol.

As a next step, Cho would like to conduct a clinical trial to see if vitamin A supplements can prevent squamous cell carcinoma. However, she added, conducting a dietary clinical trial is quite challenging on a technical level, as is ensuring that participants actually stick to the diet.

“If a clinical trial cannot be done, then a large-scale prospective study like this is the best alternative for studying diet,” Cho said.

Importance: Retinoids are bioactive forms of vitamin A that are essential in the maintenance of epithelial maturation and differentiation. Synthetic retinoids are used in chemoprevention of skin cancer among high-risk populations with potential adverse effects. Epidemiologic data on vitamin A intake and risk of cutaneous squamous cell carcinoma (SCC) are limited.
Objective: To examine whether vitamin A intake is associated with a reduction in SCC risk.
Design, Settings, and Participants: This cohort study prospectively examined intake of vitamin A and carotenoids and SCC risk in the Nurses’ Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Diet was assessed repeatedly. Incident SCC was confirmed by pathologic reports. Data analysis was performed from June 21, 2017, to December 4, 2018.
Exposures: Intakes of vitamin A, retinol, and carotenoids.
Main Outcomes and Measures: Incident SCC. Cox proportional hazards regression models were used to compute cohort-specific hazard ratios (HRs) and 95% CIs. Pooled HRs of the cohort-specific results were calculated.
Results: A total of 3978 SCC cases in 75 170 women in the Nurses’ Health Study (mean [SD] age, 50.4 [7.2] years) and 48 400 men in the Health Professionals Follow-up Study (mean [SD] age, 54.3 [9.9] years) were documented. Higher total vitamin A was associated with a reduction in SCC risk; with quintile 1 as the reference, the pooled multivariate HRs for the increasing quintiles of vitamin A intake were 0.97 (95% CI, 0.87-1.07) for quintile 2, 0.97 (95% CI, 0.80-1.17) for quintile 3, 0.93 (95% CI, 0.84-1.03) for quintile 4, and 0.83 (95% CI, 0.75-0.93) for quintile 5 (P < .001 for trend). Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk; the pooled HRs for the highest quintiles of intake compared with the lowest quintiles were 0.88 (95% CI, 0.79-0.97; P = .001 for trend) for total retinol, 0.86 (95% CI, 0.76-0.96; P = .001 for trend) for beta cryptoxanthin, 0.87 (95% CI, 0.78-0.96; P < .001 for trend) for lycopene, and 0.89 (95% CI, 0.81-0.99; P = .02 for trend) for lutein and zeaxanthin. The results were generally consistent by sex and other SCC risk factors.
Conclusions and Relevance: This study suggests that increased intake of dietary vitamin A is associated with decreased risk of incident SCC. Future studies are needed to determine whether vitamin A supplementation has a role in chemoprevention of SCC.

Jongwoo Kim, Min Kyung Park, Wen-Qing Li, Abrar A Qureshi, Eunyoung Cho

Brown University material
JAMA Dermatology abstract

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