- Vitamin 25D aka Calcifediol – is the inactive VitaminD, effectively the storage available to the body. This is what is in Vitamin D capsules
- Vitamin 1,25D aka Calcitriol — is the active amount of Vitamin D.
A few years ago there was a protocol popularized by a Ph.D. in Mechanical Engineer that saw high 1,25D and came to the mechanical conclusion that pushing 25D to Zero so there is no 1,25D. As some patients approach 0 Vitamin 25D, their symptoms reduced or disappear. Others had horrible side effects. Why? It turns out that 1,25D is your body fighting autoimmune diseases (like CFS). When you run out of Vitamin 25D, then the immune systems partially shuts down. No fighting of the infections, no symptoms.
This post will look at 25D and 1,25D:
Vitamin D is very important for patients. Studies have found that 22% – 65% of CFS patients are technically deficient ( less than 20 ng/mL) . While for Fibromyalgia 61%- 80% of Fibromyalgia patients are technically deficient.
In terms of results, significant improvement is seen when blood level of 25(OH) D exceeded 50 ng/ mL (125 nmol/L). What type of improvement do studies report?
- Decrease or elimination of headaches
- Decrease or elimination of hypersomnia
- Decrease or elimination of orthostatic intolerance
- Decrease or elimination of impaired memory
- Decrease or elimination of palpitation
- Decrease or elimination of mood disturbance
- Decrease or elimination of restless leg syndrome
- Treatment with high-dose vitamin D resulted in clinical improvement in all FM patients
- There are also studies finding some patients went into remission seen with 2000-10000 IU/day (with magnesium and phosphate supplements)
A level of at least 50+ ng/mL (125 nmol/L) appears to be a critical threshold for improvement. This is in the normal range, but towards the upper end. A few studies:
- Vitamin D and white matter abnormalities in older adults: a cross-sectional neuroimaging study
- “A significant negative correlation between vitamin D level and widespread pain index was found.”
- “Low levels of vitamin D were found associated with antithyroid antibody presence, abnormal thyroid function, increased thyroid volume, increased TSH levels, and adverse pregnancy outcome in women with autoimmune thyroid disease 
- “observational studies support a beneficial role of vitamin D in the management of thyroid disease,” 
- ” improvement became more significant when their blood level of 25(OH) D exceeded 50 ng/ mL.”
- ” a positive association of vitamin D deficiency with a variety of nonspecific bone pain, particularly in women” 
- “Musculoskeletal pain is associated with very low levels of vitamin D in men” 
- “Resolution of hypersomnia following identification and treatment of vitamin d deficiency.” 
- “Vitamin D deficiency is a major risk factor for central nervous system (CNS) demyelinating diseases including multiple sclerosis (MS)” 
- “This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system.”
- “vitamin D can suppress intracellular growth of M tuberculosis in vitro. Vitamin D also induced the expression of cathelicidin, which is involved in the first line of defense in TB patients” 
- “Vitamin D(3) skews cytokine responses toward an antiinflammatory profile,.. Candida albican” 
- Interesting that Epstain-Barr interfers with Vitamin D actions!!!! 
- “We previously demonstrated that vitamin D3 (D3) deficiency increases and D3 supplementation decreases experimental autoimmune encephalomyelitis (EAE) risk in a female-biased manner.” 
- “vitamin D is the environmental factor that most strongly influences autoimmune disease development.”
- “This review discusses the accumulating evidence pointing to a link between vitamin D and autoimmunity.” 
A large number conditions that have been documented to have a high Vitamin 1,25D result(Calcitriol) when tested.
- ” Results showed a strong positive association between these autoimmune conditions[ multiple sclerosis, lupus, psoriasis, osteoporosis, osteoarthritis, metabolic syndrome, fibromyalgia and chronic fatigue syndrome] and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state.” 
- “In granulomatous disease such as lymphoproliferative disorders, sarcoidosis, tuberculosis, and inflammatory bowel disease,”[emedicine]
- “postural orthostatic tachycardia syndrome” – remission with calcitriol treatment 
- “1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3) ), inhibits autoimmune T-cell responses in MS.”
- “1,25(OH)2D3 may represent a promising new MS treatment.” 
- Calcitriol exerts anti-inflammatory effects in keratinocytes treated with autoantibodies from a patient with bullous pemphigoid. 
- “1,25-dihydroxyvitamin D has been shown to trigger the production of antimicrobial peptides with a direct pathogen-killing capacity.” 
- “The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to inhibit the development of autoimmune diseases, including inflammatory bowel disease (IBD).” 
- “we describe 1,25(OH)(2)D(3) as an immunomodulator targeting various immune cells, including monocytes, macrophages, dendritic cells (DCs), as well as T-lymphocytes and B-lymphocytes, hence modulating both innate and adaptive immune responses.” 
Vitamin D and the Gut
- Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a “pro-inflammatory” state associated with atherosclerosis and autoimmunity .
- Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract .
Vitamin D, the gut microbiome, and the hygiene hypothesis. How does asthma begin? 
- “Finally, vitamin D is critical to the function of the gut microbiome (15).”
- Vitamin D deficiency predisposes to adherent-invasive Escherichia coli-induced barrier dysfunction and experimental colonic injury .
My own experience and limited literature has 1,25D going sky high when CFS is active (the lab retested my 1,25D because it was so high that they though that they had made an error). It returned to the normal level when I moved into remission. It is an indicator of the body fighting whatever is causing CFS. Vitamin 25D should be at the high end of the normal scale, very close to the top of the normal range.
- Health: High 25D, low 1,25D
- Sick with severe symptoms: Low 25D, high 1,25D
At 15,000 IU/day of Vitamin D3, with a 30% inefficiency — and assuming very low Vitamin D it will take approximately 70-80 days to get closer to the optimal point. Symptom improvement should not be expected to be seen for 45-90 days. For some people it may happen sooner.