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JULY 9, 2015 by MAE CHAN
High Dose Vitamin A Supplementation Encouraged By The World Health Organization Found To Shut Down Immunity

Although vitamin A deficiency is a common problem in low and middle income countries, recommendations for high-dose vitamin A supplements by the World Health Organization (WHO) has come under criticism by many researchers for its overall effect on the immune system. Researchers have now confirmed that too much vitamin A shuts down the body's immune memory and leave its defences open, says study.

The primary risks of too much vitamin A (either acute or chronic excess) are birth defects, liver abnormalities, central nervous system disorders, and lower bone mineral density that might increase osteoporosis risk. Since the American diet contains many fortified foods, the relationship between vitamin A and decreased bone density has become a greater concern.

By far the most important provitamin A carotenoid is beta-carotene; other provitamin A carotenoids are alpha-carotene and beta-cryptoxanthin. The body converts these plant pigments into vitamin A. Both provitamin A and preformed vitamin A must be metabolized intracellularly to retinal and retinoic acid, the active forms of vitamin A, to support the vitamin's important biological functions.

All vitamin A toxicity issues pertain to retinol intake (in foods and supplements containing retinol, retinyl palmitate, or retinyl acetate) and NOT food-based sources or carotenoid intake (like beta-carotene). Degrees of toxicity is also related to absorption rates.

Shuts Down Immunity

Because vitamin A is fat soluble, the body stores excess amounts, primarily in the liver, and these levels can accumulate. Although excess preformed vitamin A can have significant toxicity (known as hypervitaminosis A), large amounts of beta-carotene and other provitamin A carotenoids are not associated with major adverse effects

Researchers found that in vitro immune cells mixed with vitamin A produced fewer of the immune proteins cytokines when stimulated with mitogens and antigens.

The cells were 'trained' with different microbes (bacillus Calmette-Guerin). Yet when vitamin A was added, the microbes did not activate the immune cells, as if they had 'forgotten' they fought the intruders before.

The researchers concluded: "Short-term exposure of human monocytes to all-trans-retinoic acid [ATRA] results in long-term immune inhibition characterised by lower cytokine responses upon stimulation with a second stimulus."

Published in the Journal of Leukocyte Biology, the study shed light on why too much vitamin A may be harmful. They said the effect was due to a play-off between different histones - SUV39H2, H3K9me3 and H3K4me3 - which play a role in gene regulation. An increased expression of a histone methyltransferase, SUV39H2, suppressed others but when this was stopped cytokine production was restored.

Dr Mihai Netea, one of the researchers behind the study, said: "This study helps to explain the mechanisms of anti-inflammatory effects of vitamin A and by doing so opens the door to identifying novel ways to modulate the immune response and restore its function in situations in which it is dysregulated."

Under a 2006 document on tolerable upper limits for vitamins and minerals , the European Food Safety Authority (EFSA) set the following levels for vitamin A:

Age (years) Tolerable Upper Intake Level (UL) for preformed vitamin A (retinol and retinyl esters) (micro grams RE/day)
1-3 800
4-6 1100
7-10 1500
11-14 2000
15-17 2600
Adults + 3000

Recommendations Should Be Reviewed

Earlier this year EFSA established an average requirement of 570 micro grams retinol equivalent (RE)/day for men and 490 micro grams RE/day for women. Yet the researchers from the Radboud University Medical Centre in the Netherlands said vitamin A supplements should only be given when biological and clinical arguments for doing so were clear.

Supplemental vitamin A is known to be teratogenic or lead to reproductive toxicity. Although the World Health Organisation recommends high-dose vitamin A supplementation [VAS] in countries at risk of vitamin A deficiency; it is estimated that this intervention may not be beneficial to many populations and merits further consideration.


Mae Chan holds degrees in both physiology and nutritional sciences. She is also blogger and and technology enthusiast with a passion for disseminating information about health.

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