Vitamin D3 Deficiency Results in Dysfunctions of Immunity with Severe Fatigue and Depression in a Variety of Diseases
in vivo 28: 133-146 (2014)
ANNA DOROTHEA HOCK ad.hoeck at t-online.de
Office of Internal Medicine, Cologne, Germany
Abstract.
Recent immune data on vitamin D3 deficiency help to more clearly understand chronic fatiguing illnesses, such as autoimmune disorders, cancer and chronic fatigue syndrome (CFS). The vitamin D3 pathway is activated by stress and requires sufficient stores of precursor 25-hydroxyvitamin D3 for proper cell and immune functions. In vitamin D3 deficiency, secretion of the antimicrobial peptide cathelicidin is reduced, leading to impaired auto/xenophagy. As a result, phagocytosis, cytotoxicity, antigen processing and antigen presentation become dysregulated. In addition, vitamin D3 deficiency affects T- and B-lymphocyte activation, as well as quantity, maturation and function of regulatory natural killer T-cells and their counterparts in the gut, i.e. T-cell receptor-afi, cluster of differentiation-8aa-positive intraepithelial lymphocytes. Consequently, innate and adaptive immunity become de-regulated, with microbial effects contributing further to this. Persistent infections, chronic inflammation and fatigue follow.
Vitamin D3 substitution in such conditions may help to prevent or to ameliorate such chronic conditions, even in patients with cancer
First portion of Discussion
As shown here, vitamin D3 levels, metabolism and physiological immunoreactivity are intimately related. Insufficient levels and activities of D3 can cause immune dysregulation, resulting in various diseases, and can negatively influence the course of a variety of diseases.
Initial symptoms of low 25OHD3 levels are intermittent fatigue and recurrent infections which remit seasonally or after holiday. Insidiously, chronic fatigue syndrome may develop over time, typically promoted by stressful and exhaustive life conditions, infections, traumatic or toxic injuries. Hallmarks of chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) are severe and disabling fatigue, absence of fever in spite of general malaise resembling an acute infection, and exertion-induced aggravation of functional disabilities, as well as many additional symptoms, in particular generalized pain, sleep disorder, and gastrointestinal discomfort. Obvious organ damage is lacking, whereas reactive depressive symptoms prevail. Symptom shift to fibromyalgia (FMS) seems to be the rule when patients get older. Typically, FMS is correlated with chronic skeletal disorders of low inflammatory activity and neuropathic pains. Yet many people do not acquire CFS/ME or FMS. They suffer from clear-cut diseases that are supposed to be triggered by vitamin D3 deficiency or insufficiency. Usually, disabling fatigue accompanies chronic inflammatory and autoimmune diseases, as well as cancer, whereas less severe fatigue is usually reported by patients with chronic tissue de-generation. Severe chronic fatigue has also been observed in psychiatric diseases. Often, patients view fatigue as the most disabling among all the other disease symptoms.
Although clues are emerging that low 25OHD3 may cause chronic fatigue, altered lifestyle and behavior would also explain it, in particular with respect to patients who appear depressive or exhausted. Additionally, measurement of chronic fatigue is highly subjective. However, the diagnosis of depression or exhaustion is also subjective, in particular when the differential diagnosis of CFS/FMS or FMS is not considered. In contrast, in chronic inflammatory, autoimmune or malignant diseases, physicians appreciate fatigue undoubtedly as being disease-induced. In order to overcome usual prejudice against chronic fatigue, it should be considered that inflammation may not only induce fatigue, but also alteration of mitochondrial function, auto/xenophagy, or excitation-metabolism coupling due to lowered subcellular calcium stores (22, 166, 167).
See also VitaminDWiki
- Overview Fibromyalgia or Chronic Fatigue and vitamin D - this was the most popular web page on VitaminDWiki in 2013
- Overview Pain and Vitamin D
- Search VitaminDWiki for Fibromyalgia OR "chronic fatigue" 1850 items as of Jan 2014