Researchers have now identified the molecular pathway for flushing caused by niacin -- also known as vitamin B3 or nicotinic acid, and found in many foods -- according to a study recently completed by Dr. Robert Walters and colleagues at Duke University and funded by the National Rosacea Society. The new findings may lead to future improvements in the treatment or prevention of rosacea, which is commonly associated with flushing.
"So little is known about the flushing responses in rosacea, and the first step toward their control is to understand the nature of their causes," Dr. Walters said. "Since niacin is often a trigger factor for flushing, it was important to investigate this response at the molecular level."
He noted that this substance is an essential vitamin found in an extensive range of foods, including foods reported to trigger rosacea flare-ups in some individuals, such as beef liver, yeast, avocadoes and spinach. While niacin deficiency leads to pellagra -- a disease associated with skin problems, weakness and dementia -- he noted that it has also been associated with severe flushing in individuals taking large amounts as a supplement.
The researchers studied this process in microscopic cultures of cells and found that when one of the body's niacin receptors -- cell surface protein GPR109A -- is stimulated, both G-proteins and beta-arrestin proteins are activated. A receptor is a cellular structure that accepts the molecular structure of a specific chemical agent, and then acts on nervous tissue to produce a physiological response.
In the new study, the investigators found that niacin-like drugs stimulating only G-proteins do not induce flushing, suggesting that it is instead the beta-arrestins that cause the flushing. The beta-arrestins were further implicated when it was observed that they are required for activation of the enzyme cPLA2, which produces molecules that act directly on blood vessels in the skin to increase blood flow. As final proof, beta-arrestin activated by niacin was demonstrated to be a requirement for the flushing to occur.
"By defining the molecular pathway for flushing that begins with niacin, new therapies might be developed to block this process," Dr. Walters said. He noted that other causes of flushing may utilize the same pathway, suggesting it could also be an important mechanism for flushing in general.