Take-home message: This is a 'test-tube' study where the effects of various doses of VitD on inflammatory markers (cytokines IL-6 and TNF-alpha) were measured. VitD inhibited/reduced the expression of the inflammatory response in a dose-dependent manner - meaning that higher doses of VitD produced greater inflammatory response inhibition. Also of interest is that VitD below a certain threshold level did not effect the inflammatory response at all. Most people have a serum VitD level similar to the 15 ng/ml level tested here that showed no inhibition of inflammation. Therefore, there is a threshold level, a minimum level of VitD one must achieve - and maintain - to benefit from any anti-inflammation effects of VitD. Daily use of StarPower elevates circulating VitD levels above the minimum level necessary to block inflammation.
How Vitamin D Inhibits Inflammation
Researchers at National Jewish Health have discovered specific molecular and signaling events by which vitamin D inhibits inflammation. In their experiments, they showed that low levels of Vitamin D, comparable to levels found in millions of people, failed to inhibit the inflammatory cascade, while levels considered adequate did inhibit inflammatory signaling. They reported their results in the March 1, 2012, issue of The Journal of Immunology.
"This study goes beyond previous associations of vitamin D with various health outcomes. It outlines a clear chain of cellular events, from the binding of DNA, through a specific signaling pathway, to the reduction of proteins known to trigger inflammation," said lead author Elena Goleva, assistant professor of pediatrics at National Jewish Health. "Patients with chronic inflammatory diseases, such as asthma, arthritis and prostate cancer, who are vitamin D deficient, may benefit from vitamin D supplementation to get their serum vitamin D levels above 30 nanograms/milliliter."
Current national guidelines suggest that people should maintain a minimum blood serum level of 20 ng/ml, although there is much scientific debate about optimum levels. Vitamin D has long been known to contribute to bone health by promoting the absorption of calcium. In recent years, much attention has been paid to its possible immune and inflammatory benefits. Low vitamin D levels have been associated with several diseases including asthma, cancer, diabetes, and arthritis.
In the current study researchers examined the specific mechanisms by which vitamin D might act on immune and inflammatory pathways. They incubated human white blood cells with varying levels of vitamin D, then exposed them to lipopolysaccharide (LPS), a molecule associated with bacterial cell walls that is known to promote intense inflammatory responses.
Cells incubated with no vitamin D and in solution containing 15 ng/ml of vitamin D produced high levels of cytokines IL-6 and TNF-alpha, major actors in the inflammatory response. Cells incubated in 30 ng/ml vitamin D and above showed significantly reduced response to the LPS. The highest levels of inflammatory inhibition occurred at 50 ng/ml.
Through a complex series of experiments, the researchers identified a new location where the vitamin-D receptor appears to bind directly to DNA and activate a gene known as MKP-1. MKP-1 interferes with the inflammatory cascade triggered by LPS, which includes a molecule known as p38, and results in higher levels of IL-6 and TNF-alpha.
"This newly identified DNA-binding site for the vitamin-D receptor, and the specific pathways inhibited by higher levels of vitamin D provide a plausible mechanism for many of the benefits that have been associated with vitamin D," said Dr. Goleva. 'The fact that we showed a dose-dependent and varying response to levels commonly found in humans also adds weight to the argument for vitamin D's role in immune and inflammatory conditions."
Journal Reference:
Vitamin D is a natural anti-inflammatory substance
Following an Archives of Internal Medicine report which found vitamin D inadequacy in 75 percent of Americans, University of Missouri College of Environmental Sciences assistant professor Catherine A. Peterson announced the finding of research conducted at the University's Department of Nutritional Sciences which correlated low vitamin D levels with an increased marker of inflammation. The study was described in the July, 2008 issue of the Journal of Inflammation.
The study included 69 healthy women, aged 25 to 82, classified as being high or low in vitamin D based on ultraviolet-B exposure. Blood samples were analyzed for serum 25-hydroxyvitamin D, hormone levels, and inflammation markers.
Not surprisingly, mean serum 25-hydroxyvitamin D levels were significantly greater in those with increased sun exposure compared with those in the low D group. Dr Peterson, along with colleague Mary E Hefferman, found that the inflammatory marker tumor necrosis factor-alpha (TNF-alpha) averaged 0.79 picograms per milliliter (pg/mL) in the high vitamin D group and 1.22 pg/mL among those categorized as low in the vitamin. Higher serum 25-hydroxyvitamin D levels were also correlated with lower TNF-alpha levels. The relationship remained after adjusting the analysis for other factors. In their discussion of the findings, the authors write that although it is difficult to discern vitamin D's mechanism, a previous study found that vitamin D down-regulated TNF-alpha-associated genes.
The study is the first to determine an inverse association between TNF-alpha and vitamin D levels in a healthy population. The finding could help explain the protective association found for vitamin D against inflammatory diseases such as heart disease and rheumatoid arthritis.
"The findings reveal that low vitamin D levels negatively impact inflammation and immune response, even in healthy women," Dr Peterson commented. "Increased inflammation normally is found in people with obesity or chronic diseases; a small decrease in vitamin D levels may aggravate symptoms in people who are sick."
J Inflamm (Lond). 2008; 5: 10.
