High Levels of Active 1,25-Dihydroxyvitamin D Despite Low Levels of the 25-Hydroxyvitamin D Precursor - Implications of Dysregulated Vitamin D for Dia

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High Levels of Active 1,25-Dihydroxyvitamin D Despite Low Levels of the 25-Hydroxyvitamin D Precursor - Implications of Dysregulated Vitamin D for Diagnosis and Treatment of Chronic Disease (pp. 1-23)
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Abstract:

The active secosteroid hormone 1,25-dihydroxyvitamin-D (1,25D) often reaches excessive levels in normocalcemic patients suffering from chronic Th1 inflammatory illnesses, including sarcoidosis and rheumatoid arthritis. This is due to unregulated production of 1,25D in the mitochondria of activated macrophages. Phagocytic cells parasitized by cell wall deficient (CWD) L-forms of bacteria drive this dysfunction of vitamin D metabolism. The paracrine levels of 1,25D rise and the level of substrate 25-D falls. If studies measure only the 25D precursor, a low 25D may be misinterpreted as indicating the patient requires vitamin D supplementation. Our data show that active 1,25D hormone may be elevated, even with a low level of 25D substrate because of the inflamed macrophages’ hyperactive conversion to the active hormone. In sarcoidosis, for example, this dysregulated vitamin D conversion can mean that even a moderate intake of vitamin D through ingestion or solar exposure can cause the 1,25D hormone to become high enough to stimulate osteoclastic action, and bone resorption. Data presented here suggest that this extra-renal synthesis of 1,25D is more widespread than previously thought and because it leads to vitamin D hypersensitivity, has important implications for research, diagnosis and treatment of chronic disease. The relationship of our data to past research on the role of vitamin D in several diseases is discussed. The assay of both the active 1,25D and inactive 25D metabolites will lead to additional clinical data, potentially improving both diagnosis and care of a variety of autoimmune and other Th1 illnesses. The high recovery rate using a new antibacterial protocol (initially developed for treating sarcoidosis) and the normalization of 1,25D levels, subsequent to such treatment, emphasizes the importance of measuring both the active 1,25D hormone and the 25D substrate. It should be noted that serum must be properly handled and transported frozen in order to obtain accurate 1,25D test results. Further, an increase in 25D levels induced by vitamin D supplementation may lead to long-term disease progression by facilitating proliferation of the intracellular CWD bacterial pathogens.

 
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