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Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue? – Source: Medical Hypotheses, Oct 25, 2010

  [ 33 votes ]   [ Discuss This Article ]
By Anna Dorothea Hoeck, MD, Martin L Pall, PhD • • November 4, 2010

[Note: NF-kappaB is a regulator of cellular responses to stresses and immune response to infection. Disregulated activation of NF-kappaB has been associated with myriad illnesses from ME/CFS/FM, inflammatory and autoimmune diseases, and viral infections to cancer. Dr. Pall has been advancing the science on ways to address the dysregulated biochemical cycle that he proposes perpetuates symptoms of 'unexplained illness' since publishing his book Explaining 'Unexplained Illnesses'  in 2007. He has agreed to host a Q&A on his new findings on early in the new year.]

Chronic NF-kappaB activation has been supposed as a key event in chronic fatigue syndrome (CFS) and many other better-defined pro-inflammatory diseases. 

Knowledge about the impact of vitamin D deficiency on chronic NF-kappaB activation could open a new disease approach.

Whereas NF-kappaB activation leads at first to a pro-inflammatory immune response, later on a vitamin D-dependent anti-inflammatory response ensues.

Binding of the active vitamin D metabolite 1,25(OH)(2)D(3) to vitamin D receptor (VDR):

• Yields a transcription factor which represses NF-kappaB activation,

• And additionally modulates and down-regulates adaptive, but enhances innate immune responses,

• And improves redox balance, thus counterbalancing inflammation on multiple levels. [When redox (reduction-oxidation) is unbalanced, production of free radicals exceeds the cell's ability to readily repair the damage they can do.]

However, this built-in late counterbalance against inflammation works only when stores of calcium and 25(OH)D(3) are abundant.

Therefore a connection between lowered vitamin D-metabolism and persistent NF-kappaB activation, augmented nitrosative-oxidative stress, redox imbalance, chronic inflammation, and concomitant fatigue can be postulated.

In order to confirm this hypothesis, randomized controlled clinical studies about the clinical effects of supplementation of calcium and vitamin D(3) would be necessary in diseases characterized by persistent NF-kappaB activation and chronic inflammation and fatigue.

Source: Medical Hypotheses, Oct 25, 2010. PMID: 20980105, by Hoeck AD, Pall ML. Mariawald str. Cologne, Germany; The Tenth Paradigm Research Group and School of Molecular Biosciences, Portland, Oregon, USA. [E-mail: or]

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