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Research Newsletter-Spring/Summer 2013

Stephen Lawson

ANTI-INFECTIVE VITAMINS

Stephen Lawson
LPI Administrative Officer


Dr. Fritz Gombart of LPI has studied some surprising attributes of vitamin D for many years. The “sunshine vitamin” is not actually a vitamin because it is synthesized in the skin upon exposure to sunlight. It’s been known since the early 1920s that vitamin D deficiency in a child’s developing years causes rickets, a severe skeletal deformity. Vitamin D regulates calcium, which is crucial in bone formation. Many other functions of vitamin D have been discovered in recent years, including a role in cell differentiation, leading to the normal maturation of cells. Vitamin D deficiency has been implicated not only in rickets but also in ostemalacia (bone pain) and muscle weakness and pain. Additionally, vitamin D may be useful in blood pressure regulation and preventing cardiovascular disease, osteoporosis, and cancers of the colon, breast, and prostate.

Vitamin D plays a critical role in immunity by regulating T-lymphocyte production. In association with colleagues at Cedars-Sinai Medical Center, Dr. Gombart found that vitamin D regulates the production of an antimicrobial peptide in immune cells—neutrophils and macrophages—called cathelicidin, which can kill bacteria and viruses. This observation may explain why tuberculosis patients benefited from exposure to sunlight and is being followed up with studies on dialysis patients vulnerable to infections and increased mortality. Most recently, Dr. Gombart and colleagues found that blood levels of vitamin D up to 32 ng/mL (80 nmol/L)—a level many experts believe to be sufficient—were correlated with increasing levels of cathelicidin in blood.

In the new study, published in The Journal of Clinical Investigation in September, 2012, Dr. Gombart and his colleagues at Cedars-Sinai reported that another vitamin—niacin, or vitamin B3—also has potent immune effects. Severe niacin deficiency results in pellagra, which causes a skin rash, dementia, and death. Pellagra was common in the southeastern United States in the early 20th century when corn was widely consumed as a major dietary staple that had not been soaked in lime to release niacin and increase its bioavailability.

In the new study, researchers found that injecting nicotinamide—a form of niacin—into mice infected with Staphylococcus aureus dramatically cleared the infection, acting by increasing the activity of neutrophils through the stimulation of a transcription factor that regulates the production of antimicrobial peptides, including cathelicidin. Similar results were obtained with human blood taken from healthy volunteers and pretreated with nicotinamide before being exposed to S. aureus. These experiments demonstrate that nicotinamide may have value in preventing bacterial infections. There is also some evidence that nicotinamide may be useful in treating tuberculosis and HIV infection, as well as for killing other pathogens like K. pneumoniae and P. aeruginosa, bacteria responsible for pneumonia and sepsis, respectively. High-dose, supranutritional nicotinamide used in these experiments can cause unpleasant side effects and is not recommended for common use. More research is necessary to find out what dose or dietary intake of niacin in humans may be prophylactic.


Last updated May 2013