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A higher prevalence of vitamin D deficiency in people of color may be contributing to a higher burden of COVID-19 in minority populations. Dermatologists are encouraged to address vitamin D status in patients and recommend supplementation, which might have other health benefits.
Dermatologists are well aware that skin pigmentation affects cutaneous vitamin D synthesis, making vitamin D deficiency more common among people with skin of color. Now the COVID-19 pandemic increases the need to give due consideration to that connection, according to Pearl E. Grimes, MD.
Soon after COVID-19 case numbers started to rapidly rise worldwide, researchers began to hypothesize and investigate risk factors for infection and worse outcomes. Results showing associations with vitamin D deficiency appeared early and continued to grow.
In an article published in July 2020, Grimes and colleagues were the first to suggest that low vitamin D status could be among the variables explaining the higher burden of COVID-19 among people of color.1 Noting the need for further research to corroborate their hypothesis, the authors called on physicians to be aware of the higher prevalence of vitamin D deficiency in patients with skin of color and address the issue as a possible way to resolve the disparities in COVID-19 risks affecting minority populations.
Nine months later, information in an accumulating body of literature strengthens this call to action, said Grimes, director of The Grimes Center for Medical and Aesthetic Dermatology and founder and director of Vitiligo and Pigmentation Institute of Southern California in Los Angeles. “As we move this agenda forward, we need a cohesive effort where all physicians are talking to their patients about the importance of having a healthy level of vitamin D,” she told Dermatology Times®. “Physicians must continue to emphasize the importance of vaccination, frequent handwashing, wearing masks, and social distancing as strategies for protecting against COVID-19 infection. However, the available evidence indicates that having a healthy level of vitamin D is also important for decreasing the risk. Furthermore, data also support the idea that for individuals who develop COVID-19, having a healthy vitamin D level will increase the likelihood of having a better outcome.”
Published Evidence
Reviewing the evidence on the associations between vitamin D status and COVID-19 infection and outcomes, Grimes cited a meta-analysis published online in March 2021. Aggregating literature published through November 26, 2020, the authors identified 39 studies meeting the criteria for inclusion in their systematic review.2
Results of the meta-analysis showed linked vitamin D deficiency with increased risks of COVID-19, as well as higher composite severity and increased mortality from the disease. The findings were replicated in another meta-analysis published later in the month that reviewed 43 published studies using a literature search cutoff date of January 31, 2021.3
The relationship between vitamin D status and COVID-19 infection as it specifically applies to race and ethnicity was the topic of another study conducted at the University of Chicago, with results published online in March 2020.4 The findings further corroborate research showing an association between vitamin D deficiency (<20 ng/mL) and COVID-19 infection.
However, the study was primarily designed to investigate potential racial differences in COVID-19 risk among persons with vitamin D levels of 30 to less than 40 ng/mL, which some experts consider sufficient.
The investigators found that among Black people, the risk of testing positive for COVID-19 rose significantly, by 2.64-fold, among those with a vitamin D level of 30 to less than 40 ng/mL compared with those who had a level of at least 40 ng/mL. COVID-19 positivity rates among White people did not differ significantly when comparing the subgroup with a vitamin D level of 30 to less than 40 ng/mL and their counterparts with a higher level. The authors concluded that their findings support the idea that vitamin D supplementation could lead to COVID-19 infection rates.
Accounting for the Risk
As reviewed in the numerous published papers, including the article by Grimes, an association between vitamin D status and COVID-19 risk and outcomes is grounded on solid biologic plausibility. First, vitamin D signaling plays a key role in maintaining healthy innate and adaptive immune responses. In addition, and of particular relevance, vitamin D has been shown to mediate the induction of key antimicrobial peptides in the respiratory epithelium and inhibit production of proinflammatory cytokines that are upregulated in the COVID-19 cytokine storm.
“Two other recent meta-analyses published in the years preceding the COVID-19 pandemic linked vitamin D with risk of respiratory tract infections,” Grimes observed. “One found an increased risk of community-acquired pneumonia in persons with vitamin D levels less than 20 ng/mL, and another reported vitamin D supplementation protected against acute respiratory tract infection.”
Community Outreach
As she aims to raise health care providers’ awareness that vitamin D status may be an important modifiable risk factor for COVID-19, especially in patients with skin of color, Grimes also is taking the message directly to the public, encouraging patients to have a dialogue with their physicians about vitamin D. To accomplish this, Grimes collaborated with producer and director Felicia D. Henderson to produce an informational YouTube video, The Colors of COVID: Saving Lives and the Benefits of D-Z-C.
The 13-minute film features Henry W. Lim, MD, chairman and C.S. Livingood chair of the Department of Dermatology at Henry Ford Health System in Detroit, Michigan, alongside other medical and nutrition experts (Jonathan Sackier, MB; R. Swamy Venuturupalli, MD; and Lee Bell, BCHN) and Black celebrity activists (Tyler Perry, Angela Bassett, Nicole Ari Parker, and Jenifer Lewis). It concludes with this appeal: “Please consult your health care professional to ascertain what supplementation is right for you.”
The Bigger Picture
Hopefully, concern about contracting COVID-19 will lessen in the future. However, the need to recognize and address low vitamin D status in patients with skin of color will continue to be a priority, according to Grimes. “Clinicians need to be aware of evidence showing that vitamin D insufficiency is a risk factor for many serious diseases, including diabetes, hypertension, cardiovascular disease, autoimmune diseases, and various cancers that occur at disproportionately high rates in skin of color populations,” she said.
Grimes acknowledged that there are conflicting data about the benefit of vitamin D supplementation for reducing disease risks and improving health outcomes. In particular, skeptics cite results from the Vitamin D and Omega-3 Trial (VITAL; NCT01169259), a nationwide, randomized, placebo-controlled trial of healthy adults that found supplementation with vitamin D3 2000 IU per day did not lower the risk of invasive cancers or major cardiovascular events.5 “However, when you dive into the details of the published article, you see that the study [results] found a possible benefit for decreasing the incidence of cancer among Black participants,” she said.
While awaiting results from prospective studies that may help define the benefits of different dosing strategies, physicians should encourage patients with skin of color to take a daily vitamin D supplement, Grimes said. “The Institute of Medicine–recommended dietary allowance for vitamin D is 600 to 800 IU per day for adults, and the recommendation is based on bone health. Given the very high incidence of vitamin D deficiency in African Americans not taking supplements, higher doses are needed to achieve healthy levels.
“I think physicians can feel comfortable recommending to their adult patients that they take 1000 to 2000 IU of a vitamin D3 supplement each day,” she continued. “According to the National Academy of Medicine, most people can safely take up to 4000 IU per day without significant risk of hypercalcemia. I encourage health care providers to read the literature to develop their own knowledge base on this topic.”
References:
1. Grimes PE, Elbuluk N, Alexis AF. The relevance of vitamin D supplementation for people of color in the era of COVID-19. J Drugs Dermatol. 2020;19(7):782-783. doi:10.36849/JDD.2021.5414
2. Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CCT, Babajafari S. Association of vitamin D status with SARS-CoV-2 infection or COVID-19 severity: a systematic review and meta-analysis. Adv Nutr. Published online March 5, 2021. doi:10.1093/advances/nmab012
3. Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A. Therapeutic and prognostic role of vitamin D for COVID-19 infection: a systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol. Published online March 5, 2021.
4. Meltzer DO, Best TJ, Zhang H, et al. Association of vitamin D levels, race/ethnicity, and clinical characteristics with COVID-19 test results. JAMA Netw Open. 2021;4(3):e214117. doi:10.1016/j.jsbmb.2021.105883
5. 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. doi:10.1056/NEJMoa1809944