Vitamin A

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 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].