Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis

Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects metaanalyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: −6% (95% CI −9% to −2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was <60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference: −9% (95% CI −16% to −2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference: −47% (95% CI −73% to −21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes. Key questions What is already known? ► Vitamin C and D supplementation reduce the risk of acute respiratory tract infections (ARIs). ► Vitamin C and zinc supplementation shorten the duration of ARI symptoms. What are the new findings? ► The preventive effect of vitamin D against ARIs is greater when the diagnosis is based on clinical diagnosis or laboratory testing, rather than self-report. An optimal dosing regimen would include a daily dose ≥2000 IU vitamin D and a loading dose <60 000 IU. ► Vitamin D supplementation shortens the duration of ARI symptoms mildly, though the effect did not differ by dose. ► The preventive effect of vitamin C against ARIs is greater among men and residents of middle-income countries. ► Zinc supplementation has no effect on the risk of ARIs. What do the new findings imply? ► Micronutrient supplementation may prevent (vitamin D and C) and treat (vitamin D, C and zinc) for ARIs, including SARS-CoV-2 infection. It is unclear whether the magnitude of the effects of these..