Researchers Find Potential ‘Dark Side’ to Diets High in Beta-Carotene

New research suggests that there could be health hazards associated with consuming excessive amounts of beta-carotene.

This antioxidant is a naturally occurring pigment that gives color to foods such as carrots, sweet potatoes and certain greens. It also converts to vitamin A, and foods and supplements are the only sources for this essential nutrient.

But scientists at Ohio State University have found that certain molecules that derive from beta-carotene have an opposite effect in the body: They actually block some actions of vitamin A, which is critical to human vision, bone and skin health, metabolism and immune function.

Because these molecules derive from beta-carotene, researchers predict that a large amount of this antioxidant is accompanied by a larger amount of these anti-vitamin-A molecules, as well.

Professor Earl Harrison

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.

The findings also might explain why, in a decades-old clinical trial, more people who were heavily supplemented with beta-carotene ended up with lung cancer than did research participants who took no beta-carotene at all. The trial was ended early because of that unexpected outcome.

The scientists aren’t recommending against eating foods high in beta-carotene, and they are continuing their studies to determine what environmental and biological conditions are most likely to lead to these molecules’ production.

“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 Earl Harrison, Dean’s Distinguished Professor ofHuman Nutrition at Ohio State and lead author of the study. “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. But we have to study them further to know for sure.”

The study is scheduled for publication in the May 4, 2012, issue of theJournal of Biological Chemistry.

Previous research has already established that when beta-carotene is metabolized, it is broken in half by an enzyme, which produces two vitamin A molecules.

In this new study, the Ohio State researchers showed that some of these molecules are produced when beta-carotene is broken in a different place by processes that are not yet fully understood and act to antagonize vitamin A.

Harrison is an expert in the study of antioxidants called carotenoids, which give certain fruits and vegetables their distinctive colors. Carotenoids’ antioxidant properties are associated with protecting cells and regulating cell growth and death, all of which play a role in multiple disease processes.

For this work, he joined forces with co-authors Robert Curley, professor of medicinal chemistry and pharmacognosy, and Steven Schwartz, professor of food science and technology, both at Ohio State. Curley specializes in producing synthetic molecules in the pursuit of drug development, and Schwartz is an expert at carotenoid analysis.

Curley manufactured a series of beta-carotene-derived molecules in the lab that match those that exist in nature. The researchers then exposed these 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. What we found was they don’t activate those receptors. Instead, they inhibit activation of the receptor by retinoic acid,” Curley said. “From a drug point of view, vitamin A would be called an agonist that activates a particular pathway, and these are antagonists. They compete for the site where the agonist binds, but they don’t activate the site. They inhibit the activation that would normally be expected to occur.”

Once that role was defined, the researchers sought to determine how prevalent these molecular components might be in the human body. Analyzing blood samples obtained from six healthy human volunteers, the scientists in the Schwartz 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 compounds also have been found previously in cantaloupe and other orange-fleshed melons, suggesting humans might even absorb these molecules directly from their diet.

Harrison noted that the findings might explain the outcome of a well-known clinical trial that has left scientists puzzled for years. In that trial, people at high risk for lung cancer – smokers and asbestos workers – were given massive doses of beta-carotene over a long period of time in an attempt to lower that risk. The trial ended early because more supplemented participants developed cancer than did those who received no beta-carotene. This outcome was reinforced by results of a follow-up animal study.

“Those trials are still sending shockwaves 20 years later to the scientific community,” said Harrison, also an investigator in Ohio State’s Comprehensive Cancer Center. “What we found provides a plausible explanation of why larger amounts of beta-carotene might have led to unexpected effects in these trials.”

The research also has implications for efforts to bio-engineer staple crops in developing countries so they contain excess beta-carotene, which is considered a sustainable way to provide these populations with pro-vitamin A. Existing projects include production of golden rice in Asia, golden maize in South America and cassava in Africa.

“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.

The researchers are continuing to study these compounds, including whether food processing or specific biological processes affect their prevalence. Previous studies have suggested that oxidative stress, which can result from smoking and air pollution exposure, can lead to higher production of these anti-vitamin-A molecules, Harrison noted.

This research was supported by the National Institutes of Health and the Ohio Agricultural Research and Development Center.

Additional co-authors include Abdulkerim Eroglu, Carlo dela Sena and Sureshbabu Narayanasamy of the Department of Human Nutrition; Damian Hruszkewycz of the College of Pharmacy; and Ken Riedl and Rachel Kopec of the Department of Food Science and Technology, all at Ohio State. Harrison, Curley, Eroglu and dela Sena also are affiliated with Ohio State’s Biochemistry Program.


Nutritional Support for Wound Healing

Nutrition plays a crucial role in wound healing. Nutritional status of patients at the time of trauma or surgery influences the biochemical processes necessary for the phases of normal healing to occur. Evidence exists that vitamins A and C, zinc, arginine, glutamine, glucosamine, bromelain, Aloe vera, and Centella asiatica may be beneficial to wounded or surgical patients.


Douglas MacKay and Alan L. Miller

Nutritional support for wound healing 
Altern Med Rev 2003; 8 (4): 359-77 



Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome. Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome.


Vitamin A Supplements For Children Could Save 600,000 Lives A Year

Children in low and middle income countries should be given vitamin A supplements to prevent death and illness, concludes a study published on

The researchers argue that the effectiveness of vitamin A supplementation is now so well-established that further trials would be unethical, and they urge policymakers to provide supplements for all children at risk of deficiency.

Vitamin A is an essential nutrient that must be obtained through diet. Vitamin A deficiency in children increases vulnerability to infections like diarrhoea and measles and may also lead to blindness. Globally, the World Health Organisation estimates that 190 million children under the age of 5 may be vitamin A deficient. But, despite widespread efforts, vitamin A programmes do not reach all children who could benefit.

So a team of researchers based in the UK and Pakistan analysed the results of 43 trials of vitamin A supplementation involving over 200,000 children aged 6 months to 5 years. Differences in study design and quality were taken into account to minimise bias.

They found vitamin A supplements reduced child mortality by 24% in low and middle income countries. It may also reduce mortality and disability by preventing measles, diarrhoea and vision problems, including night blindness.

The authors say that, if the risk of death for 190 million vitamin A deficient children were reduced by 24%, over 600,000 lives would be saved each year and 20 million disability-adjusted life years (a measure of quantity and quality of life) would be gained.

Based on these results, the authors strongly recommend supplementation for children under 5 in areas at risk of vitamin A deficiency. They conclude: “The evidence for vitamin A is compelling and clear. Further trials comparing vitamin A with placebo would be unethical.”

This view is supported in an accompanying editorial by two experts at Harvard School of Public Health, who say “effort should now focus on finding ways to sustain this important child survival initiative and fine tune it to maximise the number of lives saved.”



Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ, 2011; 343: d5094.

Thorne-Lyman A, Fawzi WW. Improving child survival through vitamin A supplementation. BMJ 2011; 343: d5294.


Vitamin A Deficiency Does Not Affect Onset of Asthma

Vitamin A deficiency does not increase the risk of asthma, according to new research published online in the European Respiratory Journal.

In developing countries, vitamin A deficiency is particularly common and previous research has shown that it harms the development of the lungs.

This study aimed to assess whether vitamin A deficiency influences the development of asthma later in life.

The research, which was carried out by scientists at Johns Hopkins University in the USA and Nepalese scientists, analysed over 5,000 people living in a rural area of Nepal, where many people suffer from chronic malnutrition. They assessed whether taking vitamin A supplements at an early age altered the risk of developing of asthma.

The participants were children who had participated in two different studies. In the first, half the children were given vitamin A supplements during their pre-school years and half received a placebo. In the second study, one-third of the mothers of the children each received vitamin A supplements before, during and after pregnancy, and one-third received no supplements.

Ten to fifteen years after the studies were completed, the researchers used questionnaires and a spirometry test, which measures the amount of air in your lungs and how quickly you can breathe out, to assess lung function and whether or not the children had asthma.

The results showed that there was no difference between the children receiving supplements and those that did not receive them, in both groups of participants. The results from the spirometry tests also showed that vitamin A deficiency did not impact upon the risk of wheezing, cough, phlegm and obstructive airways.

Dr William Checkley, lead author from the John Hopkins University, said: “Contrary to what has previously been thought, our findings show that vitamin A deficiency does not lead to an increased risk of asthma. If vitamin A status was linked to asthma, the supplement taken by the study participants, would have led to some reduction in the risk of developing the condition, which we did not see.

“Whilst vitamin A deficiency does affect lung development adversely, we have found no evidence that it is linked with the development of asthma.”