From scientific studies to niche-market magazines, supplements are in the spotlight. A recent article published in Outside magazine, a publication for outdoor recreation enthusiasts, questioned the complicated relationship of sun exposure, sunscreen use, and vitamin D.1

Lower mortality rates from cardiovascular disease (CVD) and cancer have been observed in populations residing in regions with greater exposure to sunlight, a requisite for cutaneous vitamin D synthesis.2 Similarly, low serum levels of 25-hydroxyvitamin D have been linked with increased risks for CVD and cancer.2 Because of the risk for skin cancer associated with sun exposure, vitamin D supplementation has frequently been recommended as a strategy to reduce cancer and CVD risk.

However, because of the dearth of conclusive findings on this topic, both the US Preventive Services Task Force and the Institute of Medicine have stated that evidence regarding the effectiveness of vitamin D supplementation to reduce cancer and CVD risk is insufficient.3,4 Numerous study limitations have been cited, including insufficient statistical power, inadequate sample size and trial duration, and the use of low doses of vitamin D.2

The Latest on Vitamin D

In the Vitamin D and Omega-3 Trial (VITAL; NCT01169259) published January 2019 in the New England Journal of Medicine, researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, sought to address these gaps.2 They conducted a randomized, placebo-controlled trial involving 25,871 American adults who were healthy at baseline (51% women; mean age 67.1 years).

The sample included 5106 black participants, for whom the issue of vitamin D is “particularly relevant because their cutaneous synthesis of vitamin D in response to solar radiation is lower than that in persons in other racial or ethnic groups,” according to the researchers. Participants were randomly assigned to one of the following conditions: vitamin D, n-3 fatty acids, both agents, or both placebos. The median follow-up period was 5.3 years (range, 3.8-6.1 years).

The results showed no significant differences among groups in the incidence of cancer or CV events. The authors noted that their trial examined only one dose of vitamin D, and ongoing studies are investigating the effects of various doses. Additionally, a “2-year post-intervention follow-up of our cohort is ongoing to capture latency effects and increase statistical power to assess end points,” the authors wrote.

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Reconsidering Sun Exposure

Other recent findings appear to support the positive health effects of sunlight itself, with the implication that perhaps current sun exposure guidelines may be too rigid or even harmful. Multiple studies have reported beneficial effects of sun exposure on CV and metabolic parameters, including blood pressure, by means of increased plasma levels of nitric oxide metabolites.5 Research published in 2018, however, failed to demonstrate a reduction in blood pressure in 10 healthy participants after ultraviolet-A exposure that was roughly equivalent to 30 minutes of summer sun.5

Study authors did observe associated increases in plasma (nitric oxide 2−), as well as reductions in whole body oxygen utilization and resting metabolic rate, which “suggests that exposure to sunlight has a meaningful acute impact on metabolic function.”

In a 2016 prospective cohort study of 29,518 Swedish women, those who avoided sun exposure showed a shorter life expectancy than those with greater levels of sun exposure, which was “mainly due to a dose-dependent significantly increased risk of CVD and noncancer/non-CVD deaths, as compared to the moderate and high sun exposure groups,” according to the paper.6 Previous results demonstrated a 2-fold risk for mortality in the lowest vs highest sun exposure groups.7

Although women with the most active sun exposure were found to have a higher cancer-related mortality risk than the other groups, the investigators wrote that this was likely because of the longer life expectancy of these participants. They also found that nonsmokers “who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking.”

Medical Bag checked in with the following experts for further discussion regarding the implications of these various findings: Raja Sivamani, MD, MS, CAP, adjunct associate professor of clinical dermatology and director of clinical research at the University of California, Davis, and medical editor of LearnSkin.com; and Nina Shapiro, MD, director of pediatric otolaryngology and professor of head and neck surgery at the David Geffen School of Medicine at the University of California, Los Angeles, and author of the book, Hype: A Doctor’s Guide to Medical Myths, Exaggerated Claims and Bad Advice.

Medical Bag: Emerging research suggests that avoidance of sun exposure and supplementation with vitamin D may not be as beneficial as previously believed. What are your thoughts about these findings?

Dr Sivamani: We know that sunlight plays a role in a healthy lifestyle, but it does matter how it’s done. To broadly say that sunlight is good for people would discount the fact that it can also cause sunburns and deadly skin cancers. Sun avoidance and sun exposure need to be tailored to the patient. If my patient is very light skinned and burns within minutes, I will emphasize the need to be very careful with sunlight. On the other hand, if my patient has darker skin, I’m still going to discuss how sunlight can cause photoaging when done in excess, even if they don’t burn quickly.

I think prudent sun exposure has benefits beyond vitamin D, so supplementation will not make up for being outdoors, staying active, and the benefits on mood that are linked with careful sun exposure.8 The conversation about sun exposure needs to be individualized between the patient and their dermatologist.

Dr Shapiro: The notion of vitamin D supplementation in lieu of sun exposure stems from the notion that vitamin D, in its active form, is made by the skin’s exposure to sunlight. As sun exposure puts individuals at risk for skin cancers, the concept of instituting sun avoidance — which would reduce vitamin D levels — and replacement of sunlight with vitamin D supplementation has been in debate for several years.

In the VITAL study, there was no evidence that vitamin D supplementation reduced the risk for cancer and CVD. While these findings are important, there are likely many confounding factors that were not accounted for, such as diet, exercise, activity levels, family risks, and so on.

Medical Bag: Based on existing data, what are the relevant takeaways and treatment implications for clinicians?

Dr Sivamani: As noted above, clinicians should individualize the conversation to each patient, but guidelines should largely be aimed at reducing the public health epidemic of melanomas that can reduce lifespans by decades.

Dr Shapiro: The relevant takeaways are that vitamin D supplementation may not have any benefit on risk reduction for cancers and CVD. That said, the article discussing sun exposure as a potential factor for the reduction of cancer risk should be taken minimally, as sun exposure in and of itself carries known real risks. In that study, it’s possible that participants exposed to more sunlight were more physically active.

Medical Bag: What should be the focus of future efforts in these areas, in terms of research, guideline revision, or otherwise?

Dr Sivamani: A better conversation around smart sun exposure is needed: What are the right times to be outside? Is 10 to 15 minutes of sun exposure in the morning or evening adequate to get the benefits of sunlight? The next step is to have a more integrative conversation between dermatologists and other experts to understand each side of the debate and then develop guidelines that remain mindful of the deadly nature of skin cancer.

Dr Shapiro: Next steps should be to engage in longer-term studies looking specifically at serum levels of vitamin D, with and without supplementation, over long periods of time, and these serum levels’ association with positive or negative risks for cancer and CVD.

References

  1. Jacobsen R. Is Sunscreen the New Margarine? Outside. https://www.outsideonline.com/2380751/sunscreen-sun-exposure-skin-cancer-science. January 10, 2019. Accessed March 5, 2019.
  2. Manson JE, Cook NR, Lee IM, et al; VITAL Research Group. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019;380(1):33-44.  
  3. Moyer VA. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(8):558-564.
  4. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. November 30, 2010. Accessed March 5, 2019.
  5. Monaghan C, McIlvenna LC, Liddle L, et al. The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes. Eur J Appl Physiol. 2018;118(5):1043-1052.
  6. Lindqvist PG, Epstein E, Nielsen K, Landin-Olsson M, Ingvar C, Olsson H. Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort. J Intern Med. 2016;280(4):375-387.
  7. Lindqvist PG, Epstein E, Landin-Olsson M, et al. Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort. J Intern Med. 2014;276(1):77-86.
  8. Holick MF. Biological effects of sunlight, ultraviolet radiation, visible light, infrared radiation and vitamin D for health. Anticancer Res. 2016;36(3):1345-1356.