Evidence map›Paper›PMID 39449666›Full record

SynthesisNutrition reviews2025

Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies.

Ángela Alcalá-Santiago, Miguel Rodriguez-Barranco, María-José Sánchez, Ángel Gil, Belén García-Villanova, Esther Molina-Montes

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Nutrition reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ángela Alcalá-SantiagoDepartment of Nutrition and Food Science, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.ORCID 0000-0003-0648-5339
Miguel Rodriguez-BarrancoInstituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain.
María-José SánchezInstituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain.
Ángel GilInstituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain.ORCID 0000-0001-7663-0939
Belén García-VillanovaDepartment of Nutrition and Food Science, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
Esther Molina-MontesDepartment of Nutrition and Food Science, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.

Funding

Con-sejería de Salud y Consumo de la Junta de AndalucíaEuropean Regional Development Fund
6 · The paper itself

Abstract

contextExperimental and observational studies suggest that circulating micronutrients, including vitamin D (VD), may increase COVID-19 risk and its associated outcomes. Mendelian randomization (MR) studies provide valuable insight into the causal relationship between an exposure and disease outcomes.

objectivesThe aim was to conduct a systematic review and meta-analysis of causal inference studies that apply MR approaches to assess the role of these micronutrients, particularly VD, in COVID-19 risk, infection severity, and related inflammatory markers. DATA SOURCES: Searches (up to July 2023) were conducted in 4 databases. DATA EXTRACTION AND ANALYSIS: The quality of the studies was evaluated based on the MR-STROBE guidelines. Random-effects meta-analyses were conducted where possible.

resultsThere were 28 studies (2 overlapped) including 12 on micronutrients (8 on VD) and COVID-19, 4 on micronutrients (all on VD) and inflammation, and 12 on inflammatory markers and COVID-19. Some of these studies reported significant causal associations between VD or other micronutrients (vitamin C, vitamin B6, iron, zinc, copper, selenium, and magnesium) and COVID-19 outcomes. Associations in terms of causality were also nonsignificant with regard to inflammation-related markers, except for VD levels below 25 nmol/L and C-reactive protein (CRP). Some studies reported causal associations between cytokines, angiotensin-converting enzyme 2 (ACE2), and other inflammatory markers and COVID-19. Pooled MR estimates showed that VD was not significantly associated with COVID-19 outcomes, whereas ACE2 increased COVID-19 risk (MR odds ratio = 1.10; 95% CI: 1.01-1.19) but did not affect hospitalization or severity of the disease. The methodological quality of the studies was high in 13 studies, despite the majority (n = 24) utilizing 2-sample MR and evaluated pleiotropy.

conclusionMR studies exhibited diversity in their approaches but do not support a causal link between VD/micronutrients and COVID-19 outcomes. Whether inflammation mediates the VD-COVID-19 relationship remains uncertain, and highlights the need to address this aspect in future MR studies exploring micronutrient associations with COVID-19 outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022328224.

Indexed as

COVID-19InflammationMicronutrientsVitamin DBiomarkersHumansMendelian Randomization AnalysisSARS-CoV-2BiomarkersMicronutrientsVitamin Dcausal inferenceinflammatory markersMendelian randomizationmicronutrientsvitamin D

Identifiers

PMID39449666
PMCPMC12166185

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.