Can vitamin D prevent severe COVID-19 outcomes in older people?

Vitamin D deficiency is common in modern society, particularly among older people who are homebound. Vitamin D supplements in older people may have a role in preventing serious complications of COVID-19, according to data presented at AIM 2022.

“Vitamin D deficiency is associated with an impaired immune response to upper respiratory infection,” said Professor Timothy Kwok of the Department of Medicine & Therapeutics, Chinese University of Hong Kong. “As vitamin D promotes production of antimicrobial peptides from immune cells, reduces inflammatory cytokine production and endothelial dysfunction, and increases surfactant production in the lung, it may have a role in prevention of COVID-19.”

Two randomized controlled trials (RCTs) explored the effect of one mega dose of vitamin D3 (100,000 IU or 20,000 IU) on acute COVID-19 patients admitted to hospital. [BMC Med 2022;20:83; JAMA 2021;325:1053-1060] “Unfortunately, these trials did not demonstrate any significant effect of this intervention,” said Kwok.

In contrast, a real-life observational study reported positive effects of calcifediol (25-hydroxyvitamin D3 – an active form of vitamin D3) in patients hospitalized for COVID-19. Patients were assigned to the calcifediol group (532 µg on day 1, 266 µg on day 3, 7, 15 and 30; n=447; mean age, 61.8 years) or the control group (n=391; mean age, 62.4 years). Results showed that calcifediol-treated patients had significantly lower rates of intensive care unit admission (4.5 percent vs 21.0 percent; adjusted odds ratio [OR], 0.13; 95 percent confidence interval [CI], 0.07–0.23; p<0.001) and death (4.7 percent vs 15.9 percent; adjusted OR, 0.21; 95 percent CI, 0.10–0.43; <0.001) vs control. [J Clin Endocrinol Metab 2021;106:e4017-e4027]

“Active vitamin D3 [calcifediol or calcitriol] given at onset of COVID-19 may prevent serious complications in hospitalized patients with vitamin D deficiency, but monitoring of serum calcium may be required,” summarized Kwok.

“The key difference between these trials is that active vitamin D was used only in the positive trial,” explained Kwok. “Considering that there is some degree of liver dysfunction in patients with COVID-19, a mega dose of vitamin D3 [used in the negative trials] may not translate into a rapid increase of vitamin D level.”

“During the COVID-19 pandemic, there is an urgent need to improve vitamin D status quickly. Therefore, vitamin D3 supplementation at a high dose [ie, 2,000 IU/day] is recommended for elderly individuals who are homebound. The recommendation is based on a previous RCT in healthy older people, which showed that vitamin D at a dose of 2,000 IU/day did not increase the risk of hypercalcemia over 3 years,” added Kwok. “If one decides to use high-dose vitamin D, it is advisable not to use calcium supplements simultaneously.”

It is important to note that limited exposure to sunlight is a key reason for vitamin D deficiency. [J Korean Med Sci 2020;35:e50] “[Therefore,] all older people are encouraged to go out for sunshine, especially in the early morning and late afternoon,” recommended Kwok. “Also, old age homes should be designed to maximize exposure to sunlight for all residents.”