Moan J, Lagunova Z, Lindberg FA, Porojnicu AC
J Steroid Biochem Mol Biol113p217-21(2009 Feb)
Related articles: Test: 25-D, Metabolism of vitamin D and the Vitamin D Receptor
Also known as 1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol., 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. is the active form of vitamin D, binding to and activating the Vitamin D Nuclear ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. (VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response.). 1,25-D is classified as a secosteroid and is tightly regulated by the body as are all the other hormones.1) For example, one study showed that patients given 800 IU/day of vitamin D for six weeks did not show any increase in blood levels of 1,25-D.2)
When activated, the VDR transcribes hundreds of genes including those necessary for innate immune function, the body's first line of defense against pathogens.
Growing evidence suggests that:
Note that when researchers or journalists talk about vitamin D deficiency, they are invariably talking about low levels of 25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. as opposed to 1,25-D.
In the context of the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP), a 1,25-D test is largely useful at a single point in time: prior to beginning the therapy and as a general measure of overall inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue.. After starting the MP, regular dosing of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. cuts levels of 1,25-D by as much as 50% in a week's time.
By their nature, levels of 1,25-D naturally fluctuate. Women who are interested in knowing their highest level of 1,25-D should have their blood drawn mid-cycle around Day 15 or so. This is at least according to one very small 1982 study, which demonstrated that the serum concentration of 1,25-D fluctuated with the menstrual cycle.3) Levels of 1,25-D were shown to be dramatically higher near ovulation in women not on the pill.
The higher the level, the more persuasive the evidence of Th1 inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. will be for a doctor.
MP patients getting their 1,25-D levels tested should ensure the relevant instructions are closely followed including the freezing of blood samples. Over the course of at least 72 hours, 1,25-D does not appear to be degraded to any significant degree when stored at 24°C.4)
Contextual interpretation of a patient's 1,25-D result is available through the vitamin D calculator.
On the Marshall Protocol study site, 1,25-D levels are typically discussed using pg/ml units rather than pmol/L. The ratio between the two units is: 1 pg/ml = 2.4 pmol/L. To convert pmol/L into pg/ml, multiply by 0.42, as you see in this example:
72 pmol/L * 0.42 = 30 pg/ml
This is also done automatically with the vitamin D metabolite calculator.
Some laboratories establish a “normal” range for the D metabolites results based on the average of all the “healthy” persons who are tested. Since Th1 inflammation is under-diagnosed, the lab ranges are skewed high because it is assumed that it is normal for some people (who are actually sick) to have a level as high as 60 pg/ml. Therefore, many labs provide “normal” ranges for 1,25-D that are strongly skewed above a more accurate normal level.
Larger more reliable studies have found that healthy people have lower levels of 1,25-D than standard reference ranges might otherwise suggest.
These ranges are consistent with levels measured from 1,700 patients at the University of Toronto and the Merck's Physicians' Handbook.
In healthy persons, levels are 25 to 40 ng/ml (62.4 to 99.8 nmol/L) for 25(OH)D3 and 20 to 45 pg/ml (48 to 108 pmol/L) for 1,25(OH)2D3. In nutritional rickets and osteomalacia, 25(OH)D3 levels are very low, and 1,25(OH)2D3 is undetectable. A low serum phosphorus (normal: 3.0 to 4.5 mg/dL [0.97 to 1.45 mmol/L]) and a high serum alkaline phosphatase are characteristic. Serum calcium is low or normal, depending on the effectiveness of secondary hyperparathyroidism in restoring serum calcium to normal. Serum PTH is elevated, and urinary calcium is low in all forms of the disease except those associated with acidosis. In hereditary vitamin D-dependent rickets, laboratory findings vary.
Merck Manual of Diagnosis and Therapy, 15 Oct 2006 7)
Main article: Therapeutic probeA brief trial of the Marshall Protocol to see if it will generate an immunopathological response. The "gold standard" for testing whether a patient is a good candidate for the MP.
Variability in levels of 1,25-D somewhat compromises the validity of a serum 1,25-D test as an absolute measure for disease state. For this reason, candidates for the MP are advised that the ultimate measure for suitability for the MP is the therapeutic probe.
In addition, since the introduction of the Marshall Protocol, the actual 1,25D test performed by laboratories has been modified and may not be picking up the same factors as were being detected in patients with Th1 illness by the prior testing method.