COVID-19 Prevention: Vitamin D Is Still a Valid Remedy
Nicoll et al.,
COVID-19 Prevention: Vitamin D Is Still a Valid Remedy,
Journal of Clinical Medicine, doi:10.3390/jcm11226818 (Review)
Discussion of limitations and concerns for
[Jolliffe].
Nicoll et al., 18 Nov 2022, peer-reviewed, 2 authors.
Contact:
rachel.nicoll@umu.se (corresponding author).
Abstract: Journal of
Clinical Medicine
Editorial
COVID-19 Prevention: Vitamin D Is Still a Valid Remedy
Rachel Nicoll * and Michael Y. Henein
Department of Public Health and Clinical Medicine and Heart Centre, Umea University, 901 87 Umea, Sweden
* Correspondence: rachel.nicoll@umu.se
Citation: Nicoll, R.; Henein, M.Y.
COVID-19 Prevention: Vitamin D Is
Still a Valid Remedy. J. Clin. Med.
2022, 11, 6818. https://doi.org/
10.3390/jcm11226818
Received: 13 November 2022
Accepted: 16 November 2022
Published: 18 November 2022
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Seven meta-analyses and systematic reviews and three later clinical trials argued that
low vitamin D status increased susceptibility to COVID-19 and the risk of greater disease
severity and mortality [1–10]. Furthermore, there are five meta-analyses and systematic
reviews of vitamin D supplementation for the prevention of acute respiratory infection
(ARI) [11,12] and COVID-19 [13–15], as well as a later clinical trial [16], all showing that
supplementation can protect against COVID-19 infection, disease severity, and death. The
evidence could not be much more conclusive than this.
Consequently, it was surprising to learn about Joliffe et al.’s recent randomized controlled trial of vitamin D to prevent ARIs and COVID-19, which concluded that ‘Among
people aged 16 years and older with suboptimal vitamin D status, implementation of a
population level test-and-treat approach to vitamin D supplementation was not associated
with a reduction in risk of all cause acute respiratory tract infection or COVID-19’ [17].
Joliffe et al.’s UK study was a test-and-treat approach used to determine the effect of
correcting suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) < 75 nmol/L) on
the risk of contracting ARIs and COVID-19. Those with 25(OH)D < 75 nmol/L (30 ng/mL)
were randomized to six months of supplementary vitamin D at 3200 IU/day, 800 IU/day, or
no supplements. The outcome was the percentage of subjects with confirmed ARI/COVID-19.
What was different about this trial that might have caused it to fail? Analysis of
Joliffe et al’s paper gives rise to a number of observations.
Of particular importance was the treatment of participants randomized to ‘No supplementation’. Instead of being given a placebo, as would be normal in a controlled study,
they were given nothing and were informed that it was a vitamin D trial, thereby alerting
them to the fact that vitamin D supplementation could be an important infection preventive in the middle of the COVID-19 pandemic. As a result, almost 50% reported taking
their own vitamin D supplements. We do not know what level of supplementation these
participants took and we can assume that if 50% reported supplementation, the actual
number was probably higher. As Dr David Grimes noted in a BMJ Rapid Response, this
was therefore ‘a randomised UNCONTROLLED study’ [18]; consequently, any comparison
of the intervention arm with the ‘no supplementation’ arm was rendered meaningless. The
authors sought to overcome this limitation by conducting sensitivity analysis, but this is no
substitute for conducting a properly controlled..
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