Vitamin D metabolism I discover that my Calcitriol level seems a bit low (17 pg/ml), so I digged a bit in the vitamin D metabolism to understand what it means… it is more complexe than I thought! https://fr.slideshare.net/YESANNA/vitamin-dmetabolism hhttp://www.mdpi.com/2072-6643/5/7/2502/htmttp://www.wikipathways.org/index.php/Pathway:WP1531 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738984/ https://www.linkedin.com/pulse/125oh2d-calcitriol-reference-ranges-meg-mangin-rn Vitamin D in the Diet : -Ergocalciferol (D2) in plants -Cholechalciferol (D3) in animals D2 and D3 are only provitamins, they are absorbed in the small intestine under the effect of bile acids. D3 is also produced in the skin by sun exposure from cholesterol No toxicity known by sun exposure because excessive exposure to the sun destroys D3! In the liver, D3 and D2 are transformed by a specific hydrolase to 25-OH-D3 (Calcidiol), the major storage and circulatory form of vitamin D. This transformation by hydrolysation depends on CYP2R1 and CYP27A1 genes. The reference range of the total 25(OH)D level is 20-100 ng/mL. In the kidney, 25-OH-D3 is transformed by another specific hydrolase (1 alpha hydroxylase) to 1.25-OH2-D3 (Calcitriol) the active form of vitamin D for calcium homeostasis. This hydrolase depends on CYP27B1 gene. Parathormon activates the 1 alpha hydroxylase. CYP24A1 transforms 25-OH-D3 in an inactive metabolite. 1 alpha hydroxylase deficiency (and by consequence active vitamine D deficiency) can occur as a genetic disease, a renal failure, or be a result of hypoparathyroidism. Active vitamine D regulates Blood calcium, blood phosphorus by acting on kidneys, small intestine and bones. Both Calcidiol (25-OH-D3) and Calcitriol (1.25-OH2-D3) are active to boost the immune system but their mechanisms of action are different. Calcitriol is also effective to suppress auto-immunity: various epidemiological studies suggest associations between vitamin D deficiency and a higher incidence of autoimmune diseases, such as T1D, MS, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) Normal ranges are based largely on vitamin D’s effects on bone and mineral homeostasis. The optimal 25(OH)D serum level regarding other aspects of human health is still under debate. For immune-mediated diseases, experts suggest that even higher serum 25(OH)D levels may be needed to lead to positive effects. The Merck Manual of Diagnosis and Therapy (15 Oct 2006 online) listed the range of serum 1,25(OH)2D in healthy persons as 20-45 pg/mL. The 2013 edition lists the normal range as 25–65 pg/mL. The Mayo Clinic lists 18 - 78 pg/mL as the normal range. It's disappointing to note that on March 16, 2015 Labcorp raised their normal range of 1,25(OH)2D from 10 - 75 pg/mL to 19.9 - 79.3 pg/mL. As the incidence of chronic illness increases and serum 1,25(OH)2D levels rise, authorities simply increase the range of 1,25(OH)2D that is considered normal. This signifies a failure to recognize elevated 1,25(OH)2D as a sign of dysregulated vitamin D metabolism and a marker of a chronic inflammatory disease process. Studies need to be done to determine the serum level of 1,25(OH))2D in healthy populations. Using reference ranges that truly represent normal will promote accurate diagnosis of vitamin D endocrine dysfunction. Both Calcidiol and Calcitriol seem to be involved in Gastric and Intestine motility (with calcium intake) https://www.ncbi.nlm.nih.gov/pubmed/26431111 https://www.ncbi.nlm.nih.gov/pubmed/22891006 And I wish to point this case report, that could be important for us: 1-α hydroxylation defect in postural orthostatic tachycardia syndrome: remission with calcitriol supplementation. Chaudhari SA1, Sacerdote A, Bahtiyar G. Author information Abstract A 37-year-old woman presented with a history of reactive hypoglycaemia, non-classic adrenal hyperplasia (NCAH), osteopenia and fibromyalgia. After several months of palpitations, postural orthostatic tachycardia syndrome (POTS) was diagnosed by tilt table studies. Her heart rate (HR) reached 191 bpm at 60 degrees from horizontal. Investigation suggested increase in epinephrine and norepinephrine levels in response to tilt table. Her 25(OH) vitamin D level measured by immunoextraction radioimmunoassay was 35 pg/ ml (normal 9-54 pg/ml) while her 1,25(OH)(2) vitamin D3 level was 24 pg/ml (normal 30-67 pg/ml). Accordingly, she was started on calcitriol 0.25 mcg orally daily. At her next visit after 5 months, she reported remarkable improvement in her palpitations and had been working full time for the past 4 months. HR both seated and upright was 72 bpm. After 3 months, her 1,25(OH)(2) vitamin D3 level on calcitriol was 40 pg/ml. The authors suggest that 1-α hydroxylation defects should be sought and treated, if present, with calcitriol in patients with POTS. Conclusion: Would be interested to know if patients with CFS have low Calcidiol or Calcitriol which could have some effects on their immunity and auto-immunity status, and POTS!