Is vitamin D recommended for treating COVID-19?

Key Practice Points

Intervention

Q: Is vitamin D recommended for treating COVID-19?

Last Updated: 2023-07-27

Key Practice Point #1

Recommendation

Very limited evidence suggests that vitamin D may reduce disease severity in individuals with moderate to severe COVID-19; however, results are limited by small studies with imprecise results. The safety of vitamin D could not be determined due to lack of reporting. Results from ongoing studies are needed prior to providing a recommendation regarding the effectiveness and safety of vitamin D for treating COVID-19.

Evidence Summary

A 2021 Cochrane review of individuals hospitalized with moderate to severe COVID-19 (two RCTs) reported low certainty of evidence that vitamin D may decrease the need for mechanical ventilation (RR 0.52). The effects of vitamin D on mortality and adverse events could not be determined due to inconsistent and imprecise results.

A 2022 systematic review and meta-analyses of systematic reviews identified ten systematic reviews representing three to 13 primary studies of all designs reported that vitamin D2 or D3 (280,000-400,000 IU) was associated with a decreased odds of mortality (OR 0.48), a decreased odds of ICU admission (OR 0.35) and a decreased requirement for mechanical ventilation (OR 0.54). Adverse events were not reported. The results of the review represent very low certainty of evidence as results from RCTs and nonrandomized studies were combined, there was considerable overlapping of primary studies for each outcome, and the studies were small and heterogeneous.

Grade of Evidence C

Remarks

It is difficult to determine if there is an association between vitamin D deficiency and severe COVID-19 as risk factors for both conditions are similar (e.g. poor health, poor diet or a preexisting health condition such as diabetes, liver and kidney disease).

A 2021 Cochrane living systematic review (an SR that is continually updated, incorporating relevant new evidence as it becomes available) examining the effectiveness and safety of vitamin D supplements for treating individuals with COVID-19 identified three RCTs (n=356 adults), 21 ongoing studies and three completed unpublished studies awaiting classification (1). The three RCTs were conducted in Brazil, Spain and India; two studies included participants hospitalized with moderate or severe disease and one study included outpatients with mild disease. For one study of moderate to severe disease, vitamin D3 was given intravenously (0.532 mg on day 1, then 0.266 mg on days 3 and 7 then weekly until discharge). In the other two studies, vitamin D3 was given orally (200,000 IU on day 1, then 60,000 IU/day over seven days and continued in one study if serum levels were low). A meta-analysis could not be conducted due to the heterogeneity among interventions.
- For individuals with moderate to severe disease (two RCTs, n=313 participants), the evidence was very uncertain regarding an effect on all-cause mortality at hospital discharge based on inconsistent and imprecise results. Based on one RCT (n=237), low certainty evidence suggested that vitamin D may decrease the need for mechanical ventilation (RR 0.52, 95%CI 0.24 to 1.13); this was limited based on imprecise results from one study with few events. It was unknown if vitamin D was associated with the risk of adverse events based on very low certainty of evidence from one RCT (RR 2.98, 95%CI 0.12 to 72.30). Subgroup analysis from one study did not identify an effect on outcomes based on vitamin D deficiency status at baseline.
- For individuals with mild disease (one RCT, n=40), no information was provided on all-cause mortality development of severe COVID symptoms, quality of life or adverse events.

The authors indicated that no conclusions could be drawn regarding the effectiveness of vitamin D supplements for treating COVID-19 based on very low certainty evidence and inconsistency in reporting adverse events.

A systematic review and meta-analysis (SRMA) of SRMAs published from December 2019 to January 2022 examined the effect of vitamin D supplementation on morbidity and mortality in patients hospitalized with COVD-19 (2). Ten SRs were identified (including the aforementioned Cochrane review (1)) that represented three to 13 primary studies of all designs, including RCTs. There was considerable overlap among primary studies reported in each SR. The quality of reviews was assessed using AMSTAR and GRADE and most SRs were identified to have low quality evidence based on small sample sizes and heterogeneous data. Most studies used oral cholecalciferol or calcifediol; the dosage varied with booster therapies provided ranging from 280,000 to 400,000 IU. The authors reported that vitamin D supplements decreased the odds of mortality (OR 0.48, 95%CI 0.35 to 0.66, seven SRs, I²=54%), decreased the odds of ICU admission (OR 0.35, 95%CI 0.28 to 0.44, seven SRs, I²=0%) and decreased the requirement for mechanical ventilation (OR 0.54, 95%CI 0.41 to 0.71, three SRs, I²=0%). Adverse events were not reported. The authors concluded that vitamin D has the potential to prevent and treat COVID-19-related outcomes and can be safely added to COVID-19 treatment procedures; however, further trials are required to validate its effect in various heterogeneous population groups (2). Despite this conclusion, the results of this review need to be considered with caution as the review suffers from a number of limitations including combining results from RCTs and nonrandomized studies, overlapping of primary studies reported for each outcome, small studies with heterogeneous data and the lack of reporting adverse events.

Contributors

Current Contributors

Dawna Royall

Author

Elaine Anderson

Reviewer

Shée Lillejord

Reviewer, Topic Advisor

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