The primary nutritional focus of mainstream medicine centres on the belief that nutrients prevent deficiency diseases. Recommended intakes of vitamins and minerals have been created to prevent the development of the classic deficiency diseases such as scurvy, beriberi and rickets. However, recent research shows evidence that vitamins and minerals play a more diverse role in human metabolism than was previously thought. As our understanding grows, it is becoming clear that inadequate intakes of many nutrients produce diseases that have long latency periods, several of which are disease common to modern industrialised society. This paradigm shift in the metabolic function of micronutrients has been slow to develop, but the evidence that is accumulating can no longer be dismissed as unimportant or irrelevant. Vitamin D is perhaps the best example of a nutrient of which our understanding has been transformed in perhaps the last decade or so.
The classic view is that vitamin D deficiency causes rickets in children and osteomalacia in adults. These two diseases have been almost eradicated in Western nations thanks to awareness of the diseases and the fortification of certain foods with vitamin D. There is an understanding amongst mainstream medicine that if rickets or osteomalacia are not present in an individual then that person has adequate vitamin D. However, that this is not necessarily true is supported by a substantial amount of research. Vitamin D levels are measured using the metabolite 25-hydroxyvitamin D. Evidence suggests that between 25 nmol/L (below which a deficiency would manifest) and 40 nmols/L, there exists a level of vitamin D that can be described as insufficient to produce optimal health. Individuals in this range are free from the classic short latency deficiency symptoms, but in a diseased state that manifests itself in long latency deficiency disease.
The inverse association between sun exposure and cancer mortality has been known for six decades. The association between skin cancer and sun exposure, and the inverse association between skin cancer and internal cancer was originally misinterpreted to conclude that skin cancer gave immunity from internal cancers. However, researchers now know that sun exposure protects from cancer because it raises serum levels of 25(OH)D, which is required for proper immune system function. The association between skin cancer and internal cancer is just that, a correlation but not cause and effect. Calcitriol [1,25-(OH)D)] is a metabolite of 25(OH)D and many cells have 1,25-(OH)D) receptors and also express the enzyme 1-α-hydroxylase, the enzyme that converts 25(OH)D to 1,25-(OH)D. In several models of cancer, calcitriol has been shown to induce differentiation and prevent cell proliferation, which may provide evidence as to the mechanism of cancer prevention attributed to vitamin D.
Vitamin D therefore has one role as a classical endocrine hormone concerned with calcium homeostasis, and a distinct role as an autocrine concerned with modulating cell proliferation and differentiation. In its hormonal role, low levels of plasma calcium cause the release of parathyroid hormone, which causes an increase in conversion of 25(OH)D to 1,25(OH)D in the kidney. This raises plasma levels of calcium by increasing calcium absorption from the gut and increasing osteoclast activity in bone. Because the endocrine role is driven mainly by a rise in parathyroid hormone, it is independent of the circulating levels of 25(OH)D. However the autocrine role is dependent of the substrate concentrations of 25(OH)D, which in turn is related to the circulating levels of 25(OH)D. Therefore, individuals with low 25(OH)D are unable to make 1,25(OH)D in the required tissues, despite perhaps having normal circulating levels of 1, 25(OH)D.
Normal levels of 1,25(OH)D are not therefore indicative of protection from cancer because they cannot raise cellular 1,25(OH)D to high enough levels to provide the necessary cell regulation. For proper control over cell proliferation and differentiation, an individual therefore requires adequate levels of circulating 25(OH)D from either sufficient UVB exposure or sufficient dietary intake of vitamin D. Prostate cancer mortality and incidence have been shown to be associated with UV radiation exposure and with circulating plasma levels of 25(OH)D levels. African American men have the lowest serum 25(OH)D and the highest incidence of prostate cancer in America. Further evidence for the cancer protective effect of vitamin D comes from the use of 1,25(OH)D analogues as chemotherapy agents in advanced cancer at concentrations within the natural physiological range of vitamin D.
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