While past studies have established that excessive vitamin A intake can be dangerous for the foetus – with recommended limits of intake for pregnant women adjusted accordingly – the effect on blood was previously unknown. This is also the first time that the experiment has been conducted on human cells.
Past studies used fish and mice as model organisms but were unable to use human stem cells for technical and ethical reasons. Niels-Bjarne Woods and the team of researchers from the Lund Stem Cell Centre used stem cells taken from adult patients rather than human embryonic cells.
“Our results show that vitamin A in high doses has a negative effect on blood development. This suggests that there is an additional reason for pregnant women to avoid excessive intake of vitamin A during pregnancy," said Niels-Bjarne Woods.
Retinoic acid is a molecule derived from vitamin A which acts as a morphogen, sending signals to instruct how different tissue types, organs and blood cells are formed in the embryo. If levels of retinoic acid are imbalanced, the developmental process of the foetus is disturbed which can result in severe malformations.
The researchers exposed in vitro models of human stem cells to high and low levels of retinoic acid so that they would develop into haematopoietic progenitors – or blood producing – cells in an attempt to determine the impact of varying levels.
They found that by increasing the levels of retinoic acid the number of blood cells produced was decreased while a reduction in retinoic acid increased blood production by 300%.
The scientists concluded that when retinoic acids occurs at levels higher than those naturally found at embryonic sites it can act as “strong negative regulator of blood development”.
The scientists also evaluated the effect that retinoic acid had on the functionality of the blood cells it produced by measuring how capable the cells were of forming colonies. They found that for cells treated with retinoic acid there was “a complete lack of colony forming unit potential … confirming the block of hematopoietic cell production”.
No need to adjust current recommended levels
Speaking to NutraIngredients, Woods said the study should act as “a friendly reminder of the toxicity of excess vitamin A”.
“We have found that an excess of vitamin A is more hazardous than previously thought because of this effect on blood,” he said.
“But in terms of re-evaluating current recommended levels of vitamin A intake for pregnant women, we see no evidence to suggest that a change is necessary.”
The researchers’ ultimate aim is to find a way to create blood cells which could then be used for blood stem cell transplants.
Source: Stem Cell Reports
Published 10 February 2015, Vol. 4, pp 269–281
“Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Stem Cells"
Authors: R. E. Ronn, C. Guibentif, R. Moraghebi, P. Chaves, S. Saxena, B. Garcia, N. Woods