Too much vitamin A may shut down the body's ‘trained’ immunity

By Annie Harrison-Dunn contact

- Last updated on GMT

Vitamin A may shut down body's ‘trained’ immunity

Related tags: Immune system, Vitamin a deficiency

Too much vitamin A may shut down the body's immune memory and leave its defences open, says study.  

The researchers found 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-Guérin). 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) (µg RE/day)











Adults +


Earlier this year EFSA established an average requirement​ of 570 µg retinol equivalent (RE)/day for men and 490 µg 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.

"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 reduces overall child mortality by 24%. However, the effect of VAS may not always be beneficial,"​ they wrote.

Source: Journal of Leukocyte Biology​ 

98:129-136, doi:10.1189/jlb.6AB0914-416R​ 

"Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes"

Author: R. J. W. Arts, B. A. Blok, R. van Crevel, L. A. B. Joosten, P. Aaby, C. Stabell Benn and M. G. Netea

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A confusing article

Posted by Stephen Cherniske,

Nothing in the study supports the title statement that vitamin A can "shut down" the immune response to pathogens. When you read the actual text, it appears that ATRA modified cytokine production in ways that may be beneficial due to anti-inflammatory effects. In any case, we won't know until a better in vivo study is performed in mice where vitamin A is administered PO and the subsequent immune response is carefully analyzed.

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Synthetic vs. Whole Food

Posted by Chick Bowers,

Why is it not reported that Vitamin A (Synthetic) is the
Real issue here.
The body tolerates and propery uses A from food and
Whole Food suplements without Any problem,please
look at any number of studies where Synthetic versus
Whole Food actions in the body.

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This type of study misses the "real world" picture.

Posted by Michael Mooney,

Once again, looking at a nutrient, such as vitamin A, alone, without including its complementary/antagonistic partner(s) - in this case vitamin D, yields results that are not "real world." Vitamin D is typically the "driver" while its "partner," vitamin A, slows its push so that toxic effects do not occur. Numerous studies show this. Working together neither might create toxic effects.

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