https://www.mcgill.ca/oss/article/c...nutrition/will-vitamin-d-go-way-cod-liver-oil Scrutinizing the scientific literature might dampen one’s enthusiasm for the “sunshine vitamin" In many of my public lectures, I address the topic of dietary supplements and often do a rudimentary audience survey. When I ask about taking Vitamin D, the majority of adult hands go up. “Prevent osteoporosis” is the usual answer to the question as to why, although there is also a smattering of comments about reducing the risk of cancer or heart disease. This is not surprising, given the ebullient articles about Vitamin D in the lay literature. However, scrutinizing the scientific literature dampens one’s enthusiasm for the vitamin. The mention of rickets brings images of bow-legged children afflicted by this bone-softening disease during the Industrial Revolution in Britain to mind. Yet the condition was known as early as the 17th century, when it was first described by English physicians Daniel Whistler and Francis Glisson. It wasn’t until the 20th century that the disease was linked to a deficiency of a substance produced in the skin upon exposure to sunlight that came to be known as Vitamin D. That explained the prevalence of rickets during the Industrial Revolution, when the sun was obscured by smoke. Even before the intricacies of the disease were understood, there was a treatment: cod liver oil. By the early 19th century, this fish extract had already developed a folkloric reputation for treating rheumatism and joint pain, so it was readily available to try on rickets when physicians noted that children who lived in coastal areas — where fish was a dietary staple — were less affected by the disease. It worked. By 1840, the foul-tasting liquid was routinely forced down children’s throats, leaving them with a memorable experience, but at least one that didn’t include rickets. The mystery of why cod liver oil works was solved in 1922 by Elmer McCollum, who had discovered Vitamin A. McCollum found that rats develop rickets when fed a plain cereal diet. He proceeded to add various foods to their diet to see if any could prevent the disease. He finally hit upon cod liver oil and isolated vitamin D as its active ingredient. McCollum also showed that when the rats fed a cereal diet were placed outside in the sun, they were protected from rickets. This led to Vitamin D being named the “sunshine vitamin,” but exactly how it prevented rickets was not known until 1937, when Ragnar Nicolaysen at the University of Cambridge determined it was needed for the absorption of calcium from the intestine. By the 1960s, further research revealed that Vitamin D obtained from sun exposure is biologically inert and has to be converted by passage through the liver, then the kidneys into 25-hydroxyvitamin D, then into the active form, 1,25-dihydroxyvitamin D, also known as vitamin D3. Besides its role in calcium absorption, Vitamin D was also found to play a role in the functioning of osteoblasts, the cells that form new bones and heal damage to existing ones. Even more excitement about Vitamin D’s role in health emerged when it was discovered that virtually every tissue in the body has receptors for the vitamin. That raised the question of whether Vitamin D had an effect on conditions other than bone strength. This question was addressed by numerous studies, with a trial conducted by Harvard Medical School researchers being the largest and most impactive. VITAL (Vitamin D and Omega-3 Trial) randomized 25,000 adults in a placebo-controlled trial to take either 2,000 IU (50 micrograms) of Vitamin D3, 1 gram of omega-3 fats, or both. Omega-3 fats were chosen because studies had linked these fish oils to reducing blood triglycerides and lowering the risk of heart disease. The subjects were followed for five years and filled out annual questionnaires about numerous health outcomes. Given that some other studies, albeit much smaller ones, had shown benefits associated with Vitamin D supplements, the results were surprising. In VITAL, Vitamin D supplements did not prevent cardiovascular disease or cancer, did not improve stroke outcomes, did not improve cognition, did not reduce atrial fibrillation, did not change body composition or reduce knee pain. A bit of “data mining” did find fewer cases of advanced cancers detected in the Vitamin D group. An even greater surprise came when the data were analyzed for risk of fractures, something that was expected to be reduced by the bone-strengthening effect of Vitamin D. It wasn’t. There was no reduction in risk of any kind of fracture, not even in subjects who were taking 1,200 mg of supplemental calcium. Furthermore, not even individuals considered as being “deficient,” based on blood levels of Vitamin D below 20 nanograms per millilitre, were found to benefit from supplements. This would call into question the widespread testing for Vitamin D that usually prompts advice to take a supplement if the level is below 30 nanograms per millilitre. Based on VITAL, there is little evidence for taking Vitamin D supplements, but there is no harm either. When such a large, well-carried-out study comes up with disappointing results, there is motivation to dig through the data to find something to justify the massive effort and generate headlines. There was a lot of digging, and it paid off. “Taking Vitamin D Might Keep You Younger” and “Vitamin D Supplements May Slow Biological Aging,” crowed the headlines. These were prompted by researchers comparing the DNA of Vitamin D supplement takers with that of placebo takers. DNA is the genetic information-carrying molecule that is wound like a long thread into structures called chromosomes found in the nucleus of cells. The end of this thread is tightly wound, keeping the rest from unwinding. This end-piece of DNA is called a “telomere,” often being compared with the “aglet” of a shoelace. Every time a cell divides and its DNA is replicated, a bit of the telomere wears down. This erosion eventually prevents the cell from multiplying and can even lead to its death. Since telomeres shorten with each cell division, their length acts as a “biological clock” signalling aging. Preserving telomere length is therefore associated with slower aging. In VITAL, telomere length was found to be longer in subjects who took supplements, hence the blazing headlines about the vitamin slowing aging. However, this is a case of the exuberant media being keen to grab attention by converting a small step into a giant leap. Maybe the Vitamin D group had longer telomeres, but this was not reflected by any observable anti-aging effects. Indeed, as mentioned, there was no difference in the incidence of any disease between the experimental and control groups in VITAL, a trial not cherished by the supplement industry. Science, though, is a neverending story. Maybe if the trial had lasted longer than five years, benefits would have cropped up. The study also looked only at adults, and maybe Vitamin D levels are more important when children’s bones are developing. Undoubtedly, the next instalment of the Vitamin D story is just around the corner. In the meantime, I’ll go and take my 15-minute stroll in the noonday sun.