The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods reduce the risk of osteoporosis. The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease.
PMID: 18200565
Low blood levels of vitamin D have long been associated with disease, and the assumption has been that vitamin D supplements may protect against disease. However, this new research demonstrates that ingested vitamin D is immunosuppressive and that low blood levels of vitamin D may be actually a result of the disease process. Supplementation may make the disease worse.
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The VDR is at the heart of innate immunity, being responsible for expression of most of the antimicrobial peptides, which are the body's ultimate response to infection.
Molecular biology is now forcing us to re-think the idea that a low measured value of vitamin D means we simply must add more to our diet. Supplemental vitamin D has been used for decades, and yet the epidemics of chronic disease, such as heart disease and obesity, are just getting worse. "Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness," Marshall added. "Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively."
Marshall's research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine. Instead of a positive effect on gene expression, Marshall reported that his own work, as well as the work of others, shows that quite nominal doses of ingested vitamin D can suppress the proper operation of the immune system. It is a different metabolite, a secosteroid hormone called 1,25-dihydroxyvitamin D, which activates the VDR to regulate the expression of the genes. Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status.
Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse. "Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune," said J.C. Waterhouse, Ph.D., lead author of a book chapter on vitamin D and chronic disease.
"We have found that vitamin D supplementation, even at levels many consider desirable, interferes with recovery in these patients."
"We need to discard the notion that vitamin D affects a disease state in a simple way," Marshall said. "Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier."
ScienceDaily (Jan. 25, 2008)
So many studies show that supplementing vitamin D prevents cancer, diabetes type 2, auto-immune disease and cardiovascular disease.
Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D(2)] or cholecalciferol [vitamin D(3)]) on any health condition. METHODS: The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. RESULTS: We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size-adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size-adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. CONCLUSIONS: Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.
PMID: 17846391
The study seems to contain some errors:
Trevor Marshall:
"Vitamin D is a secosteroid hormone.."
Brian Wideman:
Wrong! R. Veith states emphatically that Vitamin D is not a hormone. A Vitamin D metabolite, 1,25-dihydroxyvitamin D, is a hormone. Marshall himself states that the hormone is "a different metabolite, a secosteroid
hormone called 1,25-dihydroxyvitamin D."
Trevor Marshall:
Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status.
Brian Wideman:
Wrong! According to Veith, the body can produce 25-hydroxyvitamin D, provided it has the Vitamin D precursor. This precursor is produced by the action of UV B on cholesterol. It can also be ingested in oily fish. Lacking one of these, it is false that "the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status."
Edited by s123, 14 September 2008 - 02:58 AM.