Effect of micronutrient supplementation in addition to nutritional therapy on clinical outcomes of medical inpatients: results of an updated systematic review and meta-analysis

Background: There is increasing evidence from randomized controlled trials showing that different types of nutritional support interventions improve clinical outcomes in malnourished medical inpatients. Whether trials using micronutrient supplementation in addition to nutritional therapy are superior to trials without micronutrient supplementation remains unclear. Methods: This is a secondary analysis of a systematic search and meta-analysis. We searched Cochrane Library, MEDLINE, and EMBASE electronic database from inception to December 15, 2020, for randomized controlled trials comparing the nutritional support interventions vs. usual care on all-cause mortality (primary endpoint) of medical inpatients with nutritional risk. We stratified trials based on whether or not micronutrient supplementation was used as part of the nutritional strategy. Results: We included 23 randomized controlled trials (5 trials with and 18 trials without micronutrient supplementation) with a total of 6745 patients. Overall, mortality was significantly lower in patients receiving nutritional support compared to control group patients with an odds ratio of 0.74 (95% CI 0.59–0.94, p = 0.01). There was no difference between trials with and without micronutrient supplementation on mortality (odds ratio 0.70 (95% CI 0.46–1.08) vs. 0.77 (95% CI 0.57–1.04), I² = 0%, p for subgroup difference = 0.73). Similarly, no differences in effect were found regarding non-elective readmissions and length of hospital stay. Conclusions: While nutritional support reduces mortality and improves other clinical outcomes, we did not find evidence that trials using micronutrient supplementation in addition to nutritional therapy were superior to trials with no supplementation. The role of micronutrient supplementation in addition to nutritional support needs further research.