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min D (one thousand IU/day), and the other half were advised to spend at  will encourage them to do this faster. Artery
            least twenty minutes out in the sunlight every day at midday. Both groups  calcification is one of the strongest risk factors
            saw an increase in their serum vitamin D levels, but, remarkably, the   for cardiovascular disease.
            two approaches had opposite effects on serum cholesterol. Those
            exposed to sunlight saw a statistically significant drop in their total   HIGH BLOOD PRESSURE
            cholesterol, and those taking the supplement saw a statistically significant   A 2016 paper aptly titled “Sunlight has car-
            increase.                                                     diovascular benefits independently of vitamin
               This makes sense to me because vitamin D supplements are fat-  D” argued that sunlight is a therapy option for
            soluble, which means they require the liver to synthesize cholesterol   high blood pressure, an important risk factor for
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            and release LDL particles in order to transport the vitamin D. Sunlight   cardiovascular disease.  In the paper, a scatter
            exposure stimulates cholesterol sulfate synthesis in the skin, and the   plot showing mean male population blood pres-
            sulfate moiety makes the molecule water-soluble.  This means that it can   sure versus central latitude for a large number
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            be transported in the blood without being packaged up inside an LDL   of countries (reproduced here as Figure 2) dem-
            particle. Because it is both water-soluble and fat-soluble, cholesterol   onstrated a clear linear relationship. The author
            sulfate can easily traverse water-based media to be transferred from the   argued that the reduction in blood pressure is
            membrane of a cell in the skin to the membrane of an HDL particle or a   due to sunlight’s stimulation of the release of
            red blood cell, and it can also easily be transferred to a tissue cell in need   nitric oxide from the skin.
            of additional cholesterol. Hence, sulfation induced by sunlight promotes   Nitric oxide (NO) is a well-known “gaso-
            efficient delivery of cholesterol to the tissues without the need for LDL   transmitter,” a gaseous signaling molecule that
            carrier particles. These ideas are schematized in Figure 1.   has a remarkable ability to induce a relaxation
               Calcitriol is the 1,25(OH)-D3 that is usually produced by CYP en-  of the artery wall and a resulting drop in blood
            zymes in the kidney, and it is the “active form” of vitamin D. Kidney  pressure. Endothelial dysfunction linked to car-
            failure can derail this process, and so patients with kidney failure are  diovascular disease is associated with impaired
            often given calcitriol as a supplement. However, a study published in  production of NO from arginine by eNOS, and
            2006 found it counterproductive for young adults with childhood-onset  it causes high blood pressure.  Researchers
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            end-stage renal disease to be given calcitriol supplementation, because  have recently become aware that the skin is
            calcitriol is taken up by cells in the artery wall and leads to increased  somehow able to release nitric oxide in response
            artery calcification.                                         to sunlight exposure. Exactly where the NO
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               Basically, vitamin D mobilizes calcium but doesn’t control where  comes from is somewhat of a mystery because
            calcium goes. I believe that sulfate deficiency in the vasculature drives a  it has become clear that it is not a result of direct
            conversion of the smooth muscle cells into bone-like cells, and this causes  synthesis by eNOS.
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            them to actively take up calcium and phosphate. Vitamin D supplements   A clue comes from the fact that glutathione









            FIGURE 1. Schematic of the
            differences between sunlight
            exposure and vitamin D
            supplements. Cholesterol sulfate
            and vitamin D sulfate, synthesized
            in the skin following sunlight
            exposure, can be transported freely
            in the blood, rather than requir-
            ing carrier lipid particles like LDL.









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