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Is supplementing with vitamin D the key to reducing long Covid risk?

A recent study showing that patients with long Covid had reduced vitamin D levels, raises the possibility that supplementing with the vitamin to ensure adequate levels may protect against this post-infection sequela. Rod Tucker considers the evidence.

A recent observational study published in The Journal of Clinical Endocrinology & Metabolism (JCEM), found that among patients initially hospitalised with Covid-19, those who developed long Covid had significantly lower vitamin D levels than a group of matched controls without the condition six months later.

This suggests that supplementing with the vitamin could help mitigate long Covid. Nevertheless, in order to prevent long Covid (also referred to as post-Covid condition), vitamin D should also have a role in protecting against infection with the virus in the first place.

With more than three years having passed since the start of the pandemic, is there now convincing evidence that supplementing with vitamin D reduces the risk of infection with Covid-19 virus and therefore the risk of long Covid?

Vitamin D and viral infections

The role of vitamin D in protecting against viral infections has been known for some time. In 2013, a systematic review of 11 placebo-controlled trials found that vitamin D had a protective effect against respiratory tract infections and these findings were confirmed in an update review from 2021.

Following the emergence of the Covid-19 virus, there was renewed interest in these findings, given how Covid-19 was perceived as a respiratory pathogen. Additionally, further support for the potential role of vitamin D came from observational studies demonstrating an inverse relationship between serum 25-hydroxyvitamin D concentrations and the incidence or severity of Covid-19 and how low serum vitamin D levels represented an independent risk factor for both Covid-19 infection and hospitalisation.

Given the relationship between low serum vitamin D levels and Covid-19, could supplementing with the vitamin reduce the risk of infection? The answer it seems, is only maybe. The available evidence is somewhat mixed though one study sounded a note of caution, suggesting how supplementing with the vitamin was potentially harmful.

This caution arose from an Italian study, undertaken in Lombardy during the early part of the pandemic, among those hospitalised with Covid-19. It observed that in patients previously taking taking vitamin D supplements, there was a trend towards higher mortality. As this was an observational study, the evidence was potentially unreliable. The real proof could only be derived from a randomised trial.

Fortunately, one such trial in a group of front-line healthcare workers with suboptimal vitamin D levels, found a significantly lower risk of infection among those supplementing with vitamin D. In contrast, however, a test-and-treat study in patients with suboptimal vitamin D levels, concluded that treatment with the vitamin was not associated with a reduction in the risk of Covid-19 infection.

Other work showed how giving patients hospitalised Covid-19 a vitamin D boost had no effect on their length of hospital stay, but the use of vitamin D did reduce the risk of death and intensive care unit (ICU) admission. More recently, a Spanish study comparing cholecalciferol or calcifediol supplementation, observed how both were associated with a lower risk of infection, less severe infection and a lower risk of death but only where serum vitamin D levels exceeded 30 ng/ml.

A protective role against long Covid

Although not definitive, it seems that vitamin D may well offer some protection against infection with Covid-19 and the subsequent adverse health outcomes such as ICU admission. But does vitamin D also exert a protective role against the development of long Covid and would supplementation help, particularly those with low serum levels?

Unfortunately, the answer is far from clear, but the available data does not seem to hold much promise. For instance, in one analysis of those with long Covid, characterised predominately by fatigue and reduced exercise tolerance, the authors concluded that these symptoms were independent of vitamin D levels. Other work has also failed to identify any relationship between vitamin D deficiency and post-Covid symptoms.

Part of the problem is that the risk factors for developing long Covid are less well defined than for infection. Long Covid is associated with a myriad of both physical and mental symptoms that negatively impact on quality of life. It has even been suggested that many long Covid symptoms are not directly due to the virus itself, but that the Covid virus is able to reactivate the Epstein-Barr virus.

While supplementing with vitamin D may well help to reduce the risk of developing a Covid-19 infection and the subsequent Covid-related adverse outcomes, the role of the vitamin in long Covid is more uncertain. Although the recent JCEM study highlighted that low vitamin D levels were associated with long Covid, there is an urgent need for randomised trials to explore the possible value of supplementing with the vitamin as a means of attenuating this debilitating post-infection sequela.

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