What about other diseases associated with vitamin D deficiency? What explains the significant association between depression and diabetes, hypertension, rheumatoid arthritis, cancer, advanced cancer, pancreatic cancer, and decreased bone mineral density in women? Our favorite study, showing the association between depression and bone mineral density, concludes with the following sentence: "We postulate that there may be an unmeasured third factor, such as an endogenous steroid, that is responsible for both low BMD and depression." The paper says not a word about the steroid hormone, vitamin D.Therefore, heart disease, hypertension, diabetes, rheumatoid arthritis, cancer, and low bone mineral density are all associated with depression. One parsimonious explanation is that vitamin D deficiency causes some portion of all these illnesses. Remember, all these diseases are multifactorial, so we are only talking about the percentage of the illness possibly caused by vitamin D deficiency. See Zittermann for the best review of diseases associated with vitamin D deficiency. DOES VITAMIN D AFFECT THE BRAIN?Vitamin D rapidly increases the in-vitro genetic expression of tyrosine hydroxylase (the rate-limiting enzyme for the catecholamine biosynthesis) by threefold. Summer sunlight increases brain serotonin levels twice as much as winter sunlight, a finding compatible with both bright light in the visible spectrum and vitamin D affecting mood. Vitamin D is widely involved in brain function with nuclear receptors for vitamin D localized in neurons and glial cells. Genes encoding the enzymes involved in the metabolism of vitamin D are expressed in brain cells. The reported biological effects of vitamin D in the nervous system include the biosynthesis of neurotrophic factors, inhibition of the synthesis of inducible nitric oxide synthase and increased glutathione levels, suggesting a role for the hormone in brain detoxification pathways. Evidence suggests that vitamin D may help mood but that evidence is not conclusive. (Remember, the way our medical literature system works, scientists often do not publish negative studies). The two positive studies above used vitamin D to treat seasonal affective disorder, not major depression. We were unable to find any studies in the literature in which patients with depression were treated with enough natural sunlight, artificial sunlight or plain old cholecalciferol to raise their levels to 35 ng/mL or higher. We all know how we feel after a week at the beach, but is that bright light, vitamin D, or something else?Evidence exists that major depression is associated with low vitamin D levels and that depression has increased in the last century as vitamin D levels have surely fallen. Evidence exists that depression is associated with heart disease, hypertension, diabetes, rheumatoid arthritis, cancer and low bone mineral density, all illnesses thought to be caused, in part, by vitamin D deficiency. Finally, vitamin D has profound effects on the brain including the neurotransmitters involved in major depression.
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