Beneath the Surface

Silhouette of a person’s head with orange, yellow and green over tan background.

by Ryan Barrs

Historically, daily sun exposure fulfilled the vitamin D needs of humans. Modern living, however, has made it challenging to get enough vitamin D since we spend much of our time indoors and eat few vitamin D-rich foods (e.g., oily fish). Fortified foods have helped increase our daily intake, but vitamin D deficiency is still very common.

Vitamin D insufficiency and deficiency affect 1 billion people worldwide.1 The National Health and Nutrition Examination Survey (NHANES) found that from 2001 to 2010, 28.9% of American adults were deficient in vitamin D. Non-Hispanic black American adults were the most deficient, at 71.9%, four times higher than the rate for non-Hispanic white Americans and almost twice that for Hispanics.2

Coincidentally, African Americans also have higher disease rates and mortality rates than white Americans, according to the Centers for Disease Control and Prevention.3 Socioeconomic factors are a major contributor to these health disparities, but the role of vitamin D is often ignored.

“I think it has been overlooked for a long time,” says Carol Wagner, M.D., a neonatologist at MUSC Children’s Health who studies the effects of vitamin D supplementation on human health, particularly in women and children.

Dark skin has more melanin, which reduces the amount of UVB radiation available for vitamin D conversion in the skin, and therefore needs longer sun exposure than fairer skin to produce the same amount of vitamin D.

Low vitamin D related to skin color has been associated with the severity and prevalence of multiple diseases, and new studies support recognizing vitamin D status as a biological determinant of health disparities.4,5

Maternal and pediatric health

Vitamin D is classically known for its role in skeletal health, but it modulates many different systems in the body, including the immune system. “It certainly affects calcium and bone metabolism,” explains Wagner. “But it has also been shown to affect your innate and adaptive immunity.”

Wagner recently led a study examining the relationship between vitamin D status and the vaginal microbiome during pregnancy. The study found that lower levels of circulating vitamin D in pregnant women of African descent were associated with a greater abundance of Megasphaera — a type of bacteria linked to bacterial vaginosis, an infection of the vaginal canal that can increase the risk of preterm birth.6 Women of African ancestry are twice as likely to be diagnosed with bacterial vaginosis and are more than twice as likely to give birth early preterm (<34>7,8

Early intervention between the first and second trimesters may be key to suppressing vaginal microflora associated with preterm birth.9 “It appears that vitamin D is far more important early in pregnancy than later,” said Wagner. “We now screen all pregnant women at their first prenatal visit for vitamin D deficiency.”

Wagner advocates for vitamin D supplementation during pregnancy. “A pregnant woman should take a prenatal vitamin but should also discuss her vitamin D level with her doctor,” Wagner says. “We really want women to have a level around 40 ng/mL.”

Beyond environmental impacts, genetics also contributes to differences in vitamin D status among racial groups. Dan Newton, Ph.D., a scientist in the Department of Pediatrics at MUSC, found that differences in the gene encoding vitamin D-binding protein (VDBP) affect vitamin D status in children. “Vitamin D-binding protein is one of the most abundant proteins in the blood, and it carries about 85% of vitamin D metabolites,” explains Newton.

Newton found that most African American children had VDBP gene variants associated with low vitamin D.8 Even when these children received the recommended daily allowance (RDA) of vitamin D, which is 600 IU for children older than 1 year, they did not reach sufficiency. Genotypic differences can affect responses to vitamin D supplementation, and that should be taken into consideration when creating a treatment plan.

Men’s health

The Transdisciplinary Collaborative Center (TCC) in Precision Medicine and Minority Men’s Health was established at MUSC in 2016 to tackle disparities in health outcomes among minority men. Stephen Savage, M.D., director of minimally invasive urology, is leading a project to investigate the effects of vitamin D supplementation on prostate cancer.

Savage recently found that there are biological differences in the prostate tissue between African Americans and European Americans. African Americans had a higher expression of inflammatory genes in their prostate, which may contribute to more aggressive disease progression.10 “We’re seeing inflammatory changes which appear to be related to heredity and vitamin D,” said Savage.

In a collaboration with the Department of Veterans Affairs, Savage and his colleagues showed that, compared to historical controls, supplementation at 4,000 IU/day for a year reduced tumor progression in low-risk patients undergoing active surveillance.11 Vitamin D sufficiency may therefore be beneficial for low-risk prostate cancer patients.

Savage and his collaborators in the MUSC TCC hope to unify social, environmental, and biological determinants of prostate cancer to enable more personalized treatment.

Vitamin D is not a wonder drug, but it is a foundational nutrient with complex functions in human health and disease. Establishing an effective RDA for diverse populations is important for public health. The current RDA, which is 600-800 IU for adults, may be too low for many Americans to reliably reach sufficiency (>30 ng/mL), especially with limited sun exposure.12

A dose of around 4,000 IU/day has been shown to consistently raise the vitamin D status of women and men effectively, regardless of race, without negative side effects. “Out of tens of thousands of people who have been in these trials, we are still waiting on our first adverse event,” says Bruce Hollis, Ph.D., professor emeritus in the Department of Pediatrics and a long-time vitamin D researcher at MUSC.

Future studies at MUSC and beyond will guide the understanding of vitamin D’s multifarious roles in human physiology and lead the development of more inclusive policies for vitamin D supplementation.

References

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  2. Liu X, et al. Br J Nutr. 2018;119(8):928-936. doi:10.1017/S0007114518000491.
  3. Guo W, et al. J Mol Cell Cardiol. 2014;75:131-140. doi:10.1016/j.yjmcc.2014.07.010.
  4. Wang H, et al. Aging Dis. 2017;8(3):346-353. doi:10.14336/AD.2016.1021.
  5. Weishaar T, Vergili JM. J Acad Nutr Diet. 2013;113(5):643-651. doi:10.1016/j.jand.2012.12.011.
  6. Jefferson KK, et al. J Perinatol. 2019;39(6):824-836. doi:10.1038/s41372-019-0343-8.
  7. Oliver EA, et al. Obstet Gynecol. 2018;131(2):281-289. doi:10.1097/AOG.0000000000002427.
  8. Fettweis JM, et al. Microbiology. 2014;160:2272-2282. doi:10.1099/mic.0.081034-0.
  9. Stout MJ, et al. Am J Obstet Gynecol. 2017;217(3):356.e1-356.e18. doi:10.1016/j.ajog.2017.05.030.
  10. Hardiman G, et al. Pharmacogenomics. 2016;17(10):1129-1143. doi:10.2217/pgs-2016-0025.
  11. Marshall DT, et al. J Clin Endocrinol Metab. 2012;97(7):2315-2324. doi:10.1210/jc.2012-1451.
  12. Glerup H, et al. J Intern Med. 2000;247(2):260-268. doi:10.1046/j.1365-2796.2000.00595.x.