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 requiring carrier lipid particles like LDL.
Given all of this evidence for an association between serum vitamin D levels and cancer protection, it seems obvious that vitamin D supplementation should be protective against cancer. However, a large placebo-controlled study published in 2019 by more than fifteen authors obtained disappointing results.17 The study monitored over 25,000 participants over a five-year period, restricting the study population to men over 50 years old and women over 50 years old. All participants lived in various places across the United States. In the group that received 2,000 IU of vitamin D daily, supplementation did not lower the incidence of invasive cancer or of cardiovascular events, compared to the placebo group.
SUNLIGHT AND CARDIOVASCULAR DISEASE
Researchers have long been aware that there is a direct relationship, epidemiologically, between cardiovascular disease and latitude. People who live at high latitudes have significantly higher rates of heart disease than those nearer the equator.18 Additionally, more people suffer from heart attacks in the winter than in the summer, in both northern and southern latitudes. 19
We saw above that the large placebo-controlled study did not find any benefit in vitamin D supplementation for heart disease risk. A study based in India is on of very few controlled studies where vitamin D supplementation was compared to sunlight exposure. The study involved 100 men who had been diagnosed with severe vitamin D deficiency.20 Half of them were prescribed supplemental vitamin D (1,000 IU/day), and the other half were advised to spend at least 20 minutes out in the sunlight every day during midday. Both groups saw an increase in their serum vitamin D levels, but, remarkably, the two approaches had opposite effects on serum cholesterol. Those exposed to sunlight saw a statistically significant drop in their total cholesterol, and those taking the supplement saw a statistically significant increase.
This makes sense to me because vitamin D supplements are fat-soluble, which means they require the liver to synthesize cholesterol and release LDL particles in order to transport the vitamin D. Sunlight exposure stimulates cholesterol sulfate synthesis in the skin, and the sulfate moiety makes the molecule water-soluble.3 This means that it can be transported in the blood without being packaged up inside an LDL particle. Because it is both water-soluble and fat- soluble, cholesterol sulfate can easily traverse water-based media to be transferred from the membrane of a cell in the skin to the membrane of an HDL particle or a red blood cell, and it can also easily be transferred to a tissue cell in need of additional cholesterol. Hence, sulfation induced by sunlight promotes efficient delivery of cholesterol to the tissues without the need for LDL carrier particles. These ideas are schematized in Figure 1.