High beta-carotene levels may block action of vitamin A

High intake of beta-carotene, found naturally in carrots, could actually block certain functions of vitamin A function.

A team of scientists led by Professor Earl Harrison have found that certain molecules derived from beta-carotene have an opposite effect in the body – by blocking certain actions of vitamin A, which is critical to human vision, bone and skin health, metabolism and immune function.

"We determined that these compounds are in foods, they're present under normal circumstances, and they're pretty routinely found in blood in humans, and therefore they may represent a dark side of beta-carotene," said Harrison.

"These materials definitely have anti-vitamin-A properties, and they could basically disrupt or at least affect the whole body metabolism and action of vitamin A.”

Because the anti-vitamin-A compounds are derived from beta-carotene at the same time as vitamin A, Harrison predicts that higher intakes of the antioxidant will inevitably lead to a larger amount of the potentially harmful molecules as well.

However he said that more work is needed, adding: “We have to study them further to know for sure."

Implications
Harrison explained that because vitamin A provides its health benefits by activating hundreds of genes: “This means that if compounds contained in a typical source of the vitamin are actually lowering its activity instead of promoting its benefits, too much beta-carotene could paradoxically result in too little vitamin A.”

Hesaid the findings also might explain why previous clinical trials have found that people who were heavily supplemented with beta-carotene had a higher incidence of lung cancer than participants who took no beta-carotene at all.

"Those trials are still sending shockwaves 20 years later to the scientific community," said Harrison. "What we found provides a plausible explanation of why larger amounts of beta-carotene might have led to unexpected effects in these trials."

However, the authors were keen to stress that they are not recommending against eating foods high in beta-carotene.

Study details
The US based research team manufactured a series of beta-carotene-derived molecules in the lab that match those that exist in nature. They then exposed the molecules to conditions mimicking their metabolism and action in the body.

Of the 11 synthetic molecules produced, five appeared to function as inhibitors of vitamin A action based on how they interacted with receptors that would normally launch the function of vitamin A molecules.

"The original idea was that maybe these compounds work the way vitamin A works, by activating what are called retinoic acid receptors,” said Robert Curley, who co-authored the study.

“What we found was they don't activate those receptors. Instead, they inhibit activation of the receptor by retinoic acid," he explained.

Once that role was defined, the researchers sought to determine how prevalent these molecular components might be in the human body. By analyzing blood samples obtained from six healthy human volunteers, the scientists in the lab found that some of these anti-vitamin-A molecules were present in every sample studied – suggesting that they are a common product of beta-carotene metabolism.

The researchers are continuing to study these compounds, including whether food processing or specific biological processes affect their prevalence.

Engineered vitamins
The research also has implications for industry efforts to bio-engineer staple crops that contain excess beta-carotene, which is considered a sustainable way to provide these populations with pro-vitamin A in developing countries.

"A concern is that if you engineer these crops to have unusually high levels of beta-carotene, they might also have high levels of these compounds," Harrison said.


Source: Journal of Biological Chemistry
Published online ahead of print, doi: 10.1074/jbc.M111.325142jbc.M111.325142.
“Naturally-occurring eccentric cleavage products of provitamin A beta-carotene function as antagonists of retinoic acid receptors”