ReviewInternational journal of epidemiology2015
An enigma: why vitamin A supplementation does not always reduce mortality even though vitamin A deficiency is associated with increased mortality.
Review in International journal of epidemiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 4 of them syntheses that pooled 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.
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.
Who cites it
36 citing papers in PubMed, 4 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Pooled it
- Improvement of glucose metabolism in pregnant women through probiotic supplementation depends on gestational diabetes status: meta-analysis.Scientific reports · 2020Pooled it
- Early neonatal vitamin A supplementation and infant mortality: an individual participant data meta-analysis of randomised controlled trials.Archives of disease in childhood · 2019Pooled it
- Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival: A Review.EBioMedicine · 2016Pooled it
- Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania.Vaccine · 2022Trial
- The effect of neonatal vitamin A supplementation on morbidity and mortality at 12 months: a randomized trial.International journal of epidemiology · 2016Trial
- Rethinking Vitamin A Deficiency: Its Causes, Ophthalmologic Presentation, and Management Gaps at a New England Tertiary Hospital.Nutrients · 2026Article
- Epithelial remodeling and microbial dysbiosis in the lower respiratory tract of vitamin A-deficient mouse lungs.Scientific reports · 2026Article
- Spatial Distribution and Determinants of Inadequate Vitamin A-Rich Food Consumption Among Children Aged 6-23 Months in Somalia: Evidence from the 2020 Somalia Demographic and Health Survey.Pediatric health, medicine and therapeutics · 2026Article
- Degradable poly(β-amino ester) microparticles for cleansing products and food fortification.Nature chemical engineering · 2025Article
- Vitamin A supplementation coverage and its associated factors among children aged 6-59 months in West Azernet Berbere Woreda, South West Ethiopia.BMC pediatrics · 2023Article
- Implications of Non-Specific Effects for Testing, Approving, and Regulating Vaccines.Drug safety · 2023Article
- Vitamin A supplementation and estimated number of averted child deaths in Ethiopia: 15 years in practice (2005-2019).Maternal & child nutrition · 2021Article
- Factors associated with coverage of vitamin a supplementation among Bangladeshi children: mixed modelling approach.BMC public health · 2021Article
- Perspective: Integration to Implementation (I-to-I) and the Micronutrient Forum-Addressing the Safety and Effectiveness of Vitamin A Supplementation.Advances in nutrition (Bethesda, Md.) · 2020Article
- Article
- Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism.International journal of environmental research and public health · 2019Review
- RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding.Cellular and molecular life sciences : CMLS · 2019Article
- Does India Need a Universal High-Dose Vitamin A Supplementation Program?Indian journal of pediatrics · 2019Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVitamin A deficiency (VAD) is associated with increased mortality. To prevent VAD, WHO recommends high-dose vitamin A supplementation (VAS) every 4-6 months for children aged between 6 months and 5 years of age in countries at risk of VAD. The policy is based on randomized clinical trials (RCTs) conducted in the late 1980s and early 1990s. Recent RCTs indicate that the policy may have ceased to be beneficial. In addition, RCTs attempting to extend the benefits to younger children have yielded conflicting results. Stratified analyses suggest that whereas some subgroups benefit more than expected from VAS, other subgroups may experience negative effects. METHODS AND
resultsWe reviewed the potential modifiers of the effect of VAS. The variable effect of VAS was not explained by underlying differences in VAD. Rather, the effect may depend on the sex of the child, the vaccine status and previous supplementation with vitamin A. Vitamin A is known to affect the Th1/Th2 balance and, in addition, recent evidence suggests that vitamin A may also induce epigenetic changes leading to down-regulation of the innate immune response. Thus VAS protects against VAD but has also important and long-lasting immunological effects, and the effect of providing VAS may vary depending on the state of the immune system.
conclusionsTo design optimal VAS programmes which target those who benefit and avoid those harmed, more studies are needed. Work is ongoing to define whether neonatal VAS should be considered in subgroups. In the most recent RCT in older children, VAS doubled the mortality for males but halved mortality for females. Hence, we urgently need to re-assess the effect of VAS on older children in large-scale RCTs powered to study effect modification by sex and other potential effect modifiers, and with nested immunological studies.
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.