Vitamin A

Vitamin A is synthesized in the liver of vertebrates from b-carotene. Retinol derivatives, i.e. retinal (carbon 15 becomes an aldehyde group) and retinoic acid (carbon 15 becomes a carboxylic group) act as visual pigment and hormone, respectively. Retinoic acid binds to receptor proteins in the nucleus, which then interact with transcription factors thus modulating gene expression in the development of epithelial tissue, including skin (1). Most of the biological activity of vitamin A is carried out by the above derivatives although in many research articles mention is made of vitamin A when describing the action of this vitamin.

  • Involved in reproduction, growth and development, e.g. teeth and bone formation
  • Essential for normal immune system maturation and function. There is evidence to suggest that vitamin A deficiency is a risk factor for low antibody production (2). In animal models it was shown that vitamin A supplementation enhanced cytokine production and secretory immunoglobulin A response to influenza virus infection although supplementation did not alter the clinical or virologic outcome of viral pneumonia (3). Vitamin A supplementation was also found to reduce morbidity and mortality in several infectious diseases such as severe diarrhea, measles-related pneumonia and malaria. Modulation of the immune response by vitamin A varies widely depending on the type of infection and immune response involved (4).
  • Stimulates antitumor activity in cancer cell lines. All-trans-retinoic acid exhibited an inhibitory effect on cell growth, cell cycle and alkaline phosphatase activity in human pancreatic cancer cells in vitro (5) while the retinoic acid derivative ABPN [4-amino-2- butyrylamino)phenyl(2E, 4E, 6E, 8E) -3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate] was shown to inhibit the growth of colon cancer cells (6).
  • b-carotene (pro-vitamin A) exhibits antioxidant activity (quencher of singlet oxygen)
  • Vitamin A deficiency leads to: impaired immune function, poor night vision, skin problems
  • Interactions: Vitamin E and zinc are important for the proper function of vitamin A. In animal models it was shown that a low zinc intake during pregnancy may lead to teratogenic effects and vitamin A supplementation did not affect the level of zinc in plasma and liver of pregnant rats. In contrast, the concentration of vitamin A in plasma and liver of pregnant rats was affected by the concentration of dietary zinc (7). In humans, the mechanism underlying the impaired vitamin A metabolism found in zinc deficiency is far from clear. It has been suggested that a severe zinc deficiency can impair liver retinol binding protein synthesis and cause a decrease in retinene reductase activity (zinc-dependent enzyme). Zinc-deficient humans exhibit an impaired dark adaptation (8).
  • Best food sources: liver, kidney, butter, whole milk, dark green leafy vegetables
References
1. Reichrath, J. et al. (2007) Horm.Metab.Res. 39(2) 71-84. Vitamins as hormones.
2. Ross, A.C. (2007) Vitam.Horm. 75, 197-222. Vitamin A supplementation and retinoic acid treatment in the
    regulation of antibody responses in vivo.
3. Cui, D., Moldoveanu, Z. and Stephensen, C.B. (2000) J.Nutr. 130, 1132-1139. High-level dietary vitamin A
   enhances T-helper type 2 cytokine production and secretory immunoglobulin A response to influenza A virus
    infection in BALB/c mice.
4. Semba, R.D. (1999) Proc.Nutr.Soc. 58(3) 719-727. Vitamin A and immunity to viral, bacterial and protozoan
    infections.
5. Guo, J. et al. (2006) J.Gastroenterol.Hepatol. 21(2) 443-448. Antitumor effects of all-trans-retinoic acid on
   cultured human pancreatic cancer cells.
6. Um, S.J. et al. (2003) Int.J.Cancer 107(6) 1038-1046. Novel retinoic acid derivative ABPN has potent inhibitory
   activity on cell growth and apoptosis in cancer cells.
7. Peters, A.J. et al. (1986) J.Nutr. 116(9) 1765-1771. Zinc-vitamin A interaction in pregnant and fetal rats:
   supplemental vitamin A does not prevent zinc deficiency-induced teratogenesis.
8, Nutrient Interactions (Bodwell, C.E. and Erdman, W., eds) CRC Press, Boca Raton, Fl. pp. 171-174, 1988.