Vitamin A
Classification: AATC code: A11CA01, S01X, S01XA02
Summary
A meta-analysis of the effect on mortality by vitamin A supplementation at birth in children in development countries showed a reduction of the mortality risk ratio in boys but an increase in girls at 12 months’ follow-up. A smaller study showed shorter hospital care for pneumonia in moderate malnourished girls treated with vitamin A. However, all results are difficult to interpret since there are many confounding factors.
Additional information
It has been hypothesized that vitamin A amplifies immune reactions [1]. Vitamin A may amplify the non-specific effects of vaccines on childhood mortality [1-4]. Thus, vitamin A in combination with vaccines could theoretically improve the vaccine response [1]. Vaccines may have effects on overall mortality and morbidity beyond the specific protection against the targeted disease – the so-called non-specific effects [1]. Depending on type of immune response, vitamin A may be either harmful or beneficial and also depend on patient's sex [1].
Pharmacokinetics and dosing
A randomized study of normal birth-weight newborns (2 200 boys, 2 145 girls) who received BCG vaccine and vitamin A 50 000 IU showed higher levels of retinol binding protein in boys compared to girls at the age of 4 months [5]. The same finding was shown after adjusting for CRP (C-reactive protein) in a re-analysis of a subgroup of children [6]. A randomized vitamin A vs placebo study in children aged 6 months to 2 years (555 boys, 547 girls) found similar vitamin A concentrations in boys and girls [7].
The recommended intake of vitamin A depends on age and in adults (from the age of 14 in the US) there is a difference between men and women [8].
Effects
A Vietnamese study of vitamin A supplementation compared with placebo in moderately malnourished babies (256 girls, 336 boys) found supplemented girls >12 months to have shorter hospitalization time for pneumonia [9].
Sex differences in the effect of vitamin A on the immune system have been studied in combination with vaccines.A meta-analysis (57 913 boys, 54 138 girls) of vitamin A supplementation at birth showed an increased mortality risk ratio in girls (1.2) at 12 months follow-up [10].Vitamin A co-administered with measles vaccine induced increased white blood cell counts in girls and a decrease in boys. There was a larger increase in white blood cell counts in previously un-supplemented girls compared to those previously supplemented [2]. Vitamin A shifted the effect of measles vaccine in a pro-inflammatory direction [3]. In another study, vitamin A affected in vitro cytokine production differentially depending on patients’ sex and genotype [11]. Girls who had received vitamin A but notDTP (diphtheria tetanus pertussis vaccine) had a lower spontaneous production of TNF-α and IL-10 one day after sampling [1,12].
A meta-analysis of vitamin A supplementation and the risk of miscarriage (217 726 women) showed no beneficial effect of vitamin A [13].
Adverse effects
In a Bandim Health Project study (Guinnea Bissau) children aged 6 months to 5 years received oral polio vaccine (2535 boys, 2448 girls) and were randomized to the recommended or half dose vitamin A. Girls receiving the higher dose had a higher mortality compared to boys or girls receiving the lower vitamin A dose. The incidence of diarrhea, fever and consultations at a hospital or health center was similar in boys and girls though [14].
An analysis of adverse events from vitamin A co-administered with all vaccines in children (854 boys, 819 girls) showed that the frequency of signs of increased intracranial pressure was elevated in boys but not in girls while fever 14 days after receiving live vaccines was more frequent in girls than in boys 2 weeks after vaccination. The incidence of respiratory infections after receiving vitamin A and inactivated vaccine was increased in boys but not in girls (1.44 vs 0.72). Similarly, more boys with vitamin A co-administered with DTP had local reactions [15].
Reproductive health issues
High doses of vitamin A during pregnancy can increase the risk off fetal malformations/be teratogenic [16,17]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Other information
A large review of vitamin A intake in different Western countries (74 628 women, 6 628 men) found no difference between men and women in intake of vitamin A [18].
Updated: 2018-01-04
Date of litterature search: 2017-04-10
References
- Benn CS, Balé C, Sommerfelt H, Friis H, Aaby P. Hypothesis: Vitamin A supplementation and childhood mortality: amplification of the non-specific effects of vaccines?. Int J Epidemiol. 2003;32:822-8. PubMed
- Jensen KJ, Fisker AB, Andersen A, Sartono E, Yazdanbakhsh M, Aaby P et al. The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production. Br J Nutr. 2016;115:619-28. PubMed
- Jensen KJ, Søndergaard M, Andersen A, Sartono E, Martins C, Garly ML et al. A randomized trial of an early measles vaccine at 4½ months of age in Guinea-Bissau: sex-differential immunological effects. PLoS One. 2014;9:e97536. PubMed
- Aaby P, Martins CL, Garly ML, Balé C, Andersen A, Rodrigues A et al. Non-specific effects of standard measles vaccine at 45 and 9 months of age on childhood mortality: randomised controlled trial. BMJ. 2010;341:c6495. PubMed
- Benn CS, Diness BR, Roth A, Nante E, Fisker AB, Lisse IM et al. Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial. BMJ. 2008;336:1416-20. PubMed
- Fisker AB, Lisse IM, Aaby P, Erhardt JG, Rodrigues A, Bibby BM et al. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age. Am J Clin Nutr. 2007;86:1032-9. PubMed
- Danneskiold-Samsøe N, Fisker AB, Jørgensen MJ, Ravn H, Andersen A, Balde ID et al. Determinants of vitamin a deficiency in children between 6 months and 2 years of age in Guinea-Bissau. BMC Public Health. 2013;13:172. PubMed
- Vitamin A Fact Sheet for Health Professionals. National Institutes of Health [www]. [cited 2017-04-10]. länk
- Si NV, Grytter C, Vy NN, Hue NB, Pedersen FK. High dose vitamin A supplementation in the course of pneumonia in Vietnamese children. Acta Paediatr. 1997;86:1052-5. PubMed
- Benn CS, Aaby P, Fisker AB. Neonatal vitamin A: time to move on?. Lancet. 2015;386:132-3. PubMed
- Jørgensen MJ, Fisker AB, Erikstrup C, Claesson MH, Benn CS. SNP may modify the effect of vitamin A supplementation at birth on cytokine production in a whole blood culture assay. Br J Nutr. 2012;107:615-20. PubMed
- Jørgensen MJ, Fisker AB, Sartono E, Andersen A, Erikstrup C, Lisse IM et al. The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau. Br J Nutr. 2013;109:467-77. PubMed
- Balogun OO, da Silva Lopes K, Ota E, Takemoto Y, Rumbold A, Takegata M et al. Vitamin supplementation for preventing miscarriage. Cochrane Database Syst Rev. 2016;5:CD004073. PubMed
- Benn CS, Martins C, Rodrigues A, Jensen H, Lisse IM, Aaby P. Randomised study of effect of different doses of vitamin A on childhood morbidity and mortality. BMJ. 2005;331:1428-32. PubMed
- Fisker AB, Bale C, Jørgensen MJ, Balde I, Hornshøj L, Bibby BM et al. High-dose vitamin A supplementation administered with vaccinations after 6 months of age: sex-differential adverse reactions and morbidity. Vaccine. 2013;31:3191-8. PubMed
- Livsmedelsverket Vitamin A. Livsmedelsverket [www]. [cited 2017-04-10]. länk
- Briggs GG & Freeman RK. Drugs in Pregnancy and Lactation 10th Ed. Wolters Kluwer; 2015[cited 2017-04-10]. länk
- Weber D, Grune T. The contribution of β-carotene to vitamin A supply of humans. Mol Nutr Food Res. 2012;56:251-8. PubMed
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson