Biochemical Ultrarunner: The sunshine vitamin

Vitamin D for health

In the early 20^th century, rickets, a disease caused by a softening of the bones in the legs was a major problem for children in many countries. This malady was especially evident in the Northern parts of Europe such as Scotland ¹. Interestingly, it was discovered that rickets could be prevented or even cured by the administration of cod liver oil, which is rich in many nutrients, including Vitamin A ¹. Originally it was thought that the ability of cod liver oil to cure rickets was due to the high Vitamin A in cod liver oil, however, when this was tested by feeding cod liver oil that did not contain vitamin A, the cod liver oil was still capable of curing rickets. This lead to the discovery of a new fat soluble vitamin, that was then named termed Vitamin D. Now in the 21^st century we take it for granted that very few children develop rickets, likely related to the fact that severe Vitamin D deficiency associated with rickets can be combated through the fortification of dairy products ². However, Vitamin D deficiency is still a very real concern for many individuals, and has become one of the most commonly ordered diagnostic test by primary care physicians.

There are two main forms of vitamin D that can be found in nature, Vitamin D2 and Vitamin D3. Vitamin D2 is most commonly found in plant sources, while Vitamin D3 is synthesized by animals in response to sunlight ³. Through enzymatic conversion, Vitamin D (either D2 or D3) is modified in steps by the liver and kidneys into its active form (1, 25(OH)D) ³. There are several forms of vitamin D available in supplements, and this includes both Vitamin D2 and Vitamin D3. Interestingly, if you are taking a prescription form of Vitamin D, it is most likely Vitamin D2 ³. The active form of Vitamin D (1, 25(OH)D) is not available through the diet or supplements and must be made in your body by the liver and kidneys. Keeping this fact in mind, supplying your body with adequate quantities of Vitamin D2 and Vitamin D3 is critical for producing adequate amounts of the active form of Vitamin D. Once transformed, the active form of Vitamin D will circulate through your body for only 4-8 hours ⁴, emphasizing the importance of replenishing and maintaining Vitamin D stores.

The best studied and most publicized role for Vitamin D is the role of this vitamin in promoting bone health, as indicated by its ability to protect against rickets. This is mainly achieved by improving the ability of the body to absorb dietary calcium and phosphorus, two of the main minerals that make up the skeletal system. In the absence of Vitamin D, only 10-15% of dietary calcium is absorbed and approximately 40% of phosphorous, but once Vitamin D acts on the intestinal cells to increase absorption, between 30-40% of calcium and 80% of phosphorus⁵. Related to this fact, Vitamin D also has suppressive effects on the activity of a type of cell known as an osteoclast, a cell that break down the skeleton in order to release minerals into the blood stream. By suppressing the activity of these cells, Vitamin D works to maintain bone mineral density, preventing osteoporosis and reduces the risk of stress fractures. There have been several government funded clinical trials that found daily supplementation of between 700-800 international units (IU) of Vitamin D daily reduced the relative risk of hip fractures by 26% ⁶.

Perhaps the most convincing piece of evidence supporting the critical role of vitamin D in promoting health and wellness beyond its activity on the skeletal system is the simple fact that there are cells in almost every tissue in the human body that express the Vitamin D receptor ²^,³. Upon binding to this receptor, Vitamin D regulates which genes are turned on or turned off; the gene that is regulated by Vitamin D varies depending on which tissue this process takes place. The immunodulatory effects of Vitamin D are mediated through the stimulation of immune cells resulting in the activation of anti-microbial genes ³. Alternatively, Vitamin D binding to its receptor results in suppresses the hyper-proliferation of tumor cells through changes in gene expression.

Because the conversion of Vitamin D into its activated form is highly dependent on exposure to sunlight, many studies have looked for correlative evidence between people living in various climates and an increased association with various diseases. From this epidemiological evidence, a direct role for Vitamin D is then teased out. For example, people living in latitudes that have less exposure to sunlight are known to be at an increased risk of Hodgkin’s lymphoma, prostate, colon, breast, and ovarian cancer than are those living closer to the equator ⁷^,⁸. When comparing cancer risk and Vitamin D status, individual’s with very low circulating Vitamin D levels are at a 30-50% increased risk of colon, breast, or prostate cancer and are more likely to die from these cancers ⁹^,¹⁰^,¹¹. Other negative health outcomes that have been associated with low Vitamin D status include: impaired immune function (increased risk of infection with the bacteria that causes tuberculosis) and autoimmunity (multiple sclerosis), increased risk of developing schizophrenia, Alzheimer’s disease and depression, as well as a higher incidence of cardiovascular disease, hypertension, and diabetes ³. That Vitamin D status has been correlated to the severity or incidence of this wide variety of diseases highlights how important Vitamin D is for optimal health.

When determining who is at risk for Vitamin D deficiency, it is absolutely critical to point out that nearly everyone is at some risk for Vitamin D deficiency. This is not a deficiency only seen in populations with malnutrition, malabsorption or a genetic mutation, but rather a growing epidemic that is only recently becoming recognized for its importance. That being said, there are populations who may benefit more by preventing Vitamin D deficiency, specifically the elderly who are at greater risk of osteoporosis and stress fractures, as well as pregnant women, due to the fact that the growing fetus requires Vitamin D ³. Also, those who have a familial history of diseases that are known to have a large genetic component such as Alzheimer’s and cardiovascular disease should be cognizant of maintaining adequate Vitamin D levels in order to avoid any potential compounding effects of deficiency and genetic predisposition to develop a disease.

The major cause of Vitamin D deficiency is likely attributable to limited synthesis in the skin, and this can be due to numerous factors. These factors include: sunscreen use (sunscreen of an SBF of greater than 15 blocks 99% of Vitamin D production), changes in skin pigment due to aging, and living at higher latitudes ⁹. For those living in the United States this is especially pertinent, anyone living above 35^ο latitude in the Northern hemisphere does not receive enough UVB photon exposure to stimulate Vitamin D synthesis between the months of November and March ⁹. Because Vitamin D is synthesized in kidneys and liver, persons with liver conditions are at increased risk of Vitamin D deficiency, as are those with kidney failure or chronic kidney disease. When having your Vitamin D levels checked by a physician it is important to know what defines deficient, sufficient, and insufficient ³. The consensus opinion is if serum 25-hydroxyvitamin D (a metabolite of Vitamin D) levels are below 20 nanograms per milliliter this indicates a person is Vitamin D deficient, while serum levels of greater than 30 nanograms per milliliter indicate sufficiency ⁴. Vitamin D toxicity is usually not observed until serum 25-hydroxyvitamin D levels are 150 nanograms per milliliter or greater. Equally as important are indicators of vitamin D insufficiency – a status indicating a person is at risk for deficiency, clinical tests indicate that if a person’s 25-hydroxyvitamin D levels are between 20-29 nanograms per milliliter, than this person could be considered to be Vitamin D insufficient ⁴.

Statistics vary between demographics and studies, however it is estimated that between 40-100% of elderly men in the United States and Europe are deficient for Vitamin D and that 1 billion people worldwide are Vitamin D deficient of insufficient ¹²^,¹³. Women and children are also at risk for Vitamin D deficiency, 32% of healthy young adults surveyed at a Boston Hospital were found to be Vitamin D deficient, despite taking a multivitamin and eating a diet containing sources of Vitamin D ¹⁴.

When taking steps to prevent Vitamin D deficiency it is important to understand how a person’s lifestyle influences their Vitamin D status. For many people who work from nine to five, it can be very difficult to get outside when UVB photons (10:00am-3:00pm) are present in sunlight to activate Vitamin D synthesis in the skin ⁹. The Institute of Medicine, the governing body behind the vitamin and mineral recommendations in the United States recently changed the recommended Vitamin D intake levels from 200IU a day to 400IU a day for children and adults. However, many experts agree that this is still woefully inadequate and that studies indicate supplementation of 400IU a day does not raise serum Vitamin D levels enough numerous populations that are at risk for deficiency ³. When intake of Vitamin D reaches 800IU per day, most studies show an improvement in Vitamin D status, suggesting that when dietary sources of Vitamin D are combined with supplementation, adults living in the United States likely require 800-1000IU a day in order to prevent Vitamin D deficiency ³. It should be noted that when comparing forms of Vitamin D found in supplements and food sources, Vitamin D2 is approximately 30% as effective as Vitamin D3 in normalizing serum 25-hydroxyvitamin D levels ¹⁵.

Hopefully this article has helped explain the multifactorial roles of Vitamin D in health and wellness. The amount of data and the number of diseases associated with poor Vitamin D status has been steadily on the rise and will likely continue for the next decade. The more we learn more about the role of this essential nutrient, the more we need to recognize nutritional sources that are available to help maintain adequate Vitamin D levels. There are also great resources available that explain Vitamin D and its role in health and wellness in greater detail. A recent book called “The Vitamin D Solution” by the godfather of modern Vitamin D research and the man who discovered the mechanism by which Vitamin D is produced in the skin, Dr. Michael Hollick, is an excellent resource for those interested in learning more. I had the opportunity to have lunch with Dr. Hollick several years ago immediately before the publication of “The Vitamin D Solution” and was incredibly impressed by his depth of knowledge found in this book, but also the incredibly approachable way in which it was written.

Vitamin D

1. Mellanby E. Nutrition Classics. The Lancet 1:407-12, 1919. An experimental investigation of rickets. Edward Mellanby. Nutrition reviews 1976, 34(11): 338-340.

2. Holick MF. Resurrection of vitamin D deficiency and rickets. The Journal of clinical investigation 2006, 116(8): 2062-2072.

3. Holick MF. Vitamin D deficiency. The New England journal of medicine 2007, 357(3): 266-281.

4. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Annals of epidemiology 2009, 19(2): 73-78.

5. DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American journal of clinical nutrition 2004, 80(6 Suppl): 1689S-1696S.

6. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. The American journal of clinical nutrition 2006, 84(1): 18-28.

7. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002, 94(6): 1867-1875.

8. Holick MF. Calcium plus vitamin D and the risk of colorectal cancer. The New England journal of medicine 2006, 354(21): 2287-2288; author reply 2287-2288.

9. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. The American journal of clinical nutrition 2004, 80(6 Suppl): 1678S-1688S.

10. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Journal of the National Cancer Institute 2006, 98(7): 451-459.

11. Luscombe CJ, Fryer AA, French ME, Liu S, Saxby MF, Jones PW, et al. Exposure to ultraviolet radiation: association with susceptibility and age at presentation with prostate cancer. Lancet 2001, 358(9282): 641-642.