this article and discussion about the down-side of high Vitamin D levels makes specific reference to cytokine responses.
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Vitamin D may exacerbate autoimmune disease
Date:4/8/2009
Deficiency in vitamin D has been widely regarded as contributing to autoimmune disease, but a review appearing in Autoimmunity Reviews explains that
low levels of vitamin D in patients with autoimmune disease may be a result rather than a cause of disease and that supplementing with vitamin D may actually exacerbate autoimmune disease.
Authored by a team of researchers at the California-based non-profit Autoimmunity Research Foundation, the paper goes on to point out that molecular biologists have long known that the form of vitamin D derived from food and supplements, 25-hydroxyvitamin D (25-D), is a secosteroid rather than a vitamin. Like corticosteroid medications,
vitamin D may provide short-term relief by lowering inflammation but may exacerbate disease symptoms over the long-term.
The insights are based on molecular research showing that
25-D inactivates rather than activates its native receptor - the Vitamin D nuclear receptor or VDR. Once associated solely with calcium metabolism, the
VDR is now known to transcribe at least 913 genes and largely control the innate immune response by expressing the bulk of the body's antimicrobial peptides, natural antimicrobials that target bacteria.
Written under the guidance of professor Trevor Marshall of Murdoch University, Western Australia, the paper contends that 25-D's actions must be considered in light of recent research on the Human Microbiome. Such research shows that bacteria are far more pervasive than previously thought
90% of cells in the body are estimated to be non-human increasing the likelihood that autoimmune diseases are caused by persistent pathogens, many of which have yet to be named or have their DNA characterized.
Marshall and team explain that by
deactivating the VDR and subsequently the immune response, 25-D lowers the inflammation caused by many of these bacteria but
allows them to spread more easily in the long-run. They outline how
long-term harm caused by high levels of 25-D has been missed because the bacteria implicated in autoimmune disease grow very slowly. For example, a higher incidence in brain lesions, allergies, and atopy in response to vitamin D supplementation have been noted only after decades of supplementation with the secosteroid.
Furthermore, low levels of 25-D are frequently noted in patients with autoimmune disease, leading to a current consensus that a deficiency of the secosteroid may contribute to the autoimmune disease process. However, Marshall and
team explain that these low levels of 25-D are a result, rather than a cause, of the disease process. Indeed, Marshall's research shows that
in autoimmune disease, 25-D levels are naturally down-regulated in response to VDR dysregulation by chronic pathogens. Under such circumstances,
supplementation with extra vitamin D is not only counterproductive but harmful, as it slows the ability of the immune system to deal with such bacteria.
The team points out the importance of examining alternate models of vitamin D metabolism. "Vitamin D is currently being recommended at historically unprecedented doses," states Amy Proal, one of the paper's co-authors. "Yet at the same time, the rate of nearly every autoimmune disease continues to escalate."
Contact: Paul Albert
palbert@autoimmunityresearch.org
917-887-1815
Autoimmunity Research Foundation
Source:Eurekalert
http://www.bio-medicine.org/biology-news-1/Vitamin-D-may-exacerbate-autoimmune-disease-7924-2/
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There are more Vitamin D articles at their foundation's publications and presentations page:
http://mpkb.mp-dev.com/doku.php/home:publications
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