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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.
SPRING 2020 Wise Traditions 31