In contrast to these epidemiological studies, interventional studies are still rare and small-sized. After one-year treatment with 2,000 IU (50 μg)/day cholecalciferol, inflammatory and hemostatic markers and disease activity in SLE improved (
180). A dose of 800 IU (20 μg) cholecalciferol/day applied for 2.5-10 months improved fatigue in patients with myasthenia gravis (
10). Rehabilitation outcomes improved after vitamin D supplementation in those with multiple illnesses (
16). 4,000 IU (100 μcg) cholecalciferol/day for one year reduced recurrent infections of the respiratory tract significantly (
169). Importantly, a pilot study showed clearly improved mitochondrial oxidative function after normalization of 25OHD3 levels in 12 severely vitamin D3-deficient patients with chronic fatigue and myopathy (
166).
However, large interventional studies and clear evidence for usefulness of vitamin D3 treatment are still lacking. One cause of obvious reluctance to undertake larger interventional studies may be the ongoing debate and overall uncertainty about doses and possible side-effects of vitamin D3 treatment.
[original paragraph]
Timely diagnosis of underlying vitamin D3 deficiency or insufficiency and adequate treatment, even at the stage of unexplained chronic fatigue, is warranted.
Measuring the blood levels of the precursor 25OHD3 is easy and cost-effective. In contrast, an elevated level of the active metabolite 1,25(OH)2D3 does not indicate vitamin D sufficiency, but might be an important clue to calcium deficiency, presumably associated with autoimmunity (
2). Sufficiency is defined as 25OHD3 levels above 30-100 ng/ml (75-250 nmol/l). Levels of 10-30 ng/ml (25-75 nmol/l) indicate insufficiency, those below 10 ng/ml (25 nmol/l) clear-cut deficiency.
Therapy is equally easy. Cholecalciferol can be applied orally, and continuous daily substitution is recommended. The therapeutic dose ranges from 4,000 to 10,000 IU (100-250 μg)/day. Higher doses of about 10,000 IU/day, and concurrent mineral, or other co-factor substitution are warranted in order to overcome eventual vitamin D3 resistance, such as in calcium deficiency. In contrast to drugs usually recommended for chronic inflammatory, autoimmune or malignant diseases, cholecalciferol is very inexpensive.
[original paragraph]
Early treatment of chronic fatigue and recurrent infections might prevent full-blown CFS/ME. Elevating 25OHD3 levels in early stages of diseases may ameliorate the course, and shorten the time needed for induction therapy, thus lowering total treatment costs. Deleterious side-effects, often life-threatening, of modern biological, cytostatic or immunosuppressive compounds may be avoided, or at least reduced. Incidence of relapse and treatment resistance may decrease, as well as the burden of disease, and therapy costs. However, usefulness and cost-effectiveness of vitamin D3 co-treatment needs further investigation from high-powered and carefully designed clinical studies.
