Both of these compounds, which are called stilbenoids, worked in synergy with vitamin D and had a significant impact in raising the expression of the human cathelicidin antimicrobial peptide, or CAMP gene, that is involved in immune function.
The research was published today in Molecular Nutrition and Food Research, in studies supported by the National Institutes of Health.
Almost a decade ago, researchers discovered that
pterostilbene helps regulate blood sugar and might help fight type-2 diabetes. The finding adds to a growing list of reasons to eat colorful fruit, especially blueberries, which are rich in compounds known as antioxidants. These molecules battle cell and DNA damage involved in cancer, heart disease, diabetes and perhaps also brain degeneration.
Pterostilbene works as well as the commercial drug ciprofibrate to lower the levels of fats (lipids) and triglycerides -- but they worked even more accurately. They are so specific that side-effects are non-existent.
"Out of a study of hundreds of compounds, just these two popped right out," said Adrian Gombart, an LPI principal investigator and associate professor in the OSU College of Science. "Their synergy with vitamin D to increase CAMP gene expression was significant and intriguing. It's a pretty interesting interaction."
Resveratrol has been the subject of dozens of studies for a range of possible benefits for muscle strength, anti-inflammatories, metabolism, neurodegenerative diseases, diabetes, cardiovascular disease and even cancer. This research is the first to show a clear synergy with vitamin D that increased CAMP expression by several times, scientists said.
The CAMP gene itself is also the subject of much study, as it has been shown to play a key role in the "innate" immune system, or the body's first line of defense and ability to combat bacterial infection. The innate immune response is especially important as many antibiotics increasingly lose their effectiveness.
Grapes don't have to be fermented to contain this antioxidant. It's actually found in the skin of red grapes along with other nutrients, such as minerals manganese and potassium and vitamins K, C and B1.
A strong link has been established between adequate vitamin D levels and the function of the CAMP gene, and the new research suggests that certain other compounds may play a role as well.
Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the CAMP gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation.
Stilbenoids are compounds produced by plants to fight infections, and in human biology appear to affect some of the signaling pathways that allow vitamin D to do its job, researchers said. It appears that combining these compounds with vitamin D has considerably more biological impact than any of them would separately.
Continued research could lead to a better understanding of how diet and nutrition affect immune function, and possibly lead to the development of therapeutically useful natural compounds that could boost the innate immune response, the researchers said in their report.
Despite the interest in compounds such as resveratrol and pterostilbene, their bioavailability remains a question, the researchers said. Some applications that may evolve could be with topical use to improve barrier defense in wounds or infections, they said.
The regulation of the CAMP gene by vitamin D was discovered by Gombart, and researchers are still learning more about how it and other compounds affect immune function. The unique biological pathways involved are found in only two groups of animals -- humans and non-human primates.
Considering that most people have insufficient levels of vitamin D and that nearly 1 billion people worldwide are deficient, properly designed supplementation studies in humans will be important for determining the benefits from the interaction of the CAMP gene and serum levels of vitamin D on immune system function.