Assessing the Effects of Micronutrients on Viral Infection in Humans: A Systematic Review and Meta-AnalysistextShim, Samuel HyunwoocreatorLiu, SiminAdvisorZullo, AndrewReaderBrown University. Department of Epidemiologysponsor2021ix, 33 p.born digitalThesis (Sc. M.)--Brown University, 2021thesesBackground: Although many micronutrients are known to have important roles in the regulation of the immune system, the clinical efficacies of micronutrients in the prevention of viral infections remain uncertain. We therefore conducted a systematic review and meta-analysis of available experimental and observational studies evaluating the roles of micronutrients in relation to viral infection risk in humans. Objective: The objective was to synthesize evidence regarding the roles of micronutrient supplementation and viral infections among apparently healthy humans. Design: We systematically searched PUBMED/MEDLINE and Embase for both experimental and observational studies that directly assessed the roles of vitamin A, vitamin C, vitamin D, vitamin E, and zinc supplementations in relation to measles, norovirus, HIV, HPV, and respiratory tract infections in humans. Screening of studies was conducted by two independent assessors and agreement obtained via consensus. Quantitative meta-analytical assessment was performed on eligible studies. Risk of bias and quality assessment of the included studies were performed using the Cochrane risk-of-bias assessment tool and the Newcastle-Ottawa Scale. Results: Of 1,039 studies screened, we identified 22 relevant studies comprising 260,566 participants (40,997 from 17 randomized controlled trials, 3,127 from one prospective cohort study, 202,990 from three retrospective cohort studies, and 13,452 participants from one cross-sectional study). Three of these 22 studies investigated vitamin A, five investigated vitamin C, nine investigated vitamin D, two investigated vitamin E, and three investigated zinc. We quantitatively evaluated 10 randomized controlled trials (1,931 infection cases out of 4,532 participants) using a random-effects model. Although large heterogeneities were identified across available studies (I2 = 54%; 95% CI: [5%, 77%]), there appeared to be some benefits associated with supplementation of vitamin C (1,000 mg/day), vitamin D (2,000 IU/day), vitamin E (200 IU/day), and zinc (184 mg/day) on lower risk of viral respiratory tract infection (RR: 0.83; 95% CI: [0.70, 0.98]). Conclusions: Supplementation of vitamin C, vitamin D, vitamin E, and zinc may lower viral respiratory tract infection risk in apparently healthy individuals. However, available studies were limited by small sample size and large amount of heterogeneities in study design and characteristics of outcomes reported in diverse populations. Findings of this systematic review and meta-analysis not only support the need for large-scale randomized intervention studies to determine the balance of benefits or risks associated with micronutrient supplementation in the primary prevention for viral infection but guide the specific design for such a large intervention trial in humans.Virus diseasesNutritionInfectionEnglishRPB20210607