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Getting Personal: Omics of the Heart

Sep 27, 2017

Jane Ferguson:                Hi, everyone. Welcome to episode six of our podcast. I'm Jane Ferguson, the current chair of the Professional Education and Publications Committee of the Functional Genomics and Translational Biology Council of the American Heart Association. It's July as we're recording this, so hopefully all you listeners in the Northern Hemisphere are enjoying the summer and taking a break to catch up on your podcast queue, maybe while relaxing at the beach or while navigating the twists and turns of the airport security line.

                                           In honor of summer, we're doing something a little different this month and featuring a bite-sized podcast with some research about how your vacation plans might be affecting your heart disease risk. For all our friends in the Southern Hemisphere, I'm sorry that this may be less relevant to you right now, but hopefully you're having a nice winter and enjoying the ability to go outside without sweating. On to our topic, let's talk about the defining feature of summer, sunlight.

                                           Humans synthesize vitamin D in response to sun exposure, and vitamin D deficiency can be associated with multiple adverse health consequences, particularly on bone health. However, there have also been reports of association between vitamin D and cardiovascular health. Prompted by observations that cardiovascular events peak during winter months and follow a geographical gradient with higher event rates at higher latitudes, the hypothesis was put forward in the early 1980s that CVD events are mediated by UV exposure through modulation of vitamin D status.

                                           This has been supported by a number of different strands of evidence. Large-scale meta-analyses of population data have found that low levels of circulating vitamin D, as estimated from measurements of serum 25-hydroxy vitamin D, are associated with increased risk of all-cause mortality and with increased risk of cardiovascular events and mortality.

                                           As summarized in an article from earlier this month in PLOS ONE, by Lars Rejnmark and Rolph Jorde, meta-analyses of randomized clinical trials have found a beneficial effect of vitamin D supplementation on blood pressure, depression, respiratory tract infections, and mortality. However, most find no beneficial effects, including no effects on CVD or diabetes. Some key limitations of these studies were that they often included a relatively small number of subjects, were conducted in individuals who were not vitamin D deficient, or used relatively low levels of vitamin D supplementation.

                                           What was lacking in the field until recently was a large-scale, randomized trial to definitively address whether increasing vitamin D levels in the general population would have a protective effect on cardiovascular health. The results of such a large-scale clinical trial of vitamin D supplementation were recently published in the June 2017 issue of JAMA Cardiology. The first and last authors were Robert Scraggs from the University of Auckland and Carlos Camargo from Harvard Medical School.

                                           They recruited over 5,000 individuals aged 50 to 84 for monthly supplementation with a hundred thousand international units of vitamin D compared with placebo control. This dose is sufficient to maintain serum 25-hydroxy vitamin D above 35 nanograms per mil. The study was continued for around three years, and events were ascertained from ICD-10 codes. While baseline 25-hydroxy vitamin D levels were inversely associated with CVD risk during follow-up, there was no significant difference in CVD events between the supplementation and placebo group.

                                           There were some limitations to this study, including a lower than expected event rate, a median follow-up time of only 3.3 years, and the study was not powered to analyze effects in subgroups of individuals with vitamin D deficiency. However, overall, this study adds to the evidence against a benefit for large-scale vitamin D supplementation.

                                           Another recent clinical trial of vitamin D and calcium supplementation published in JAMA in March of this year by Joan Lappe and Sharon McDonnell found no statistically significant effect on cancer incidents in a four-year, double-blind, placebo-controlled, population-based, randomized clinical trial in over 2,000 healthy, post-menopausal women, although there did appear to be a nonsignificant trend towards lower incidents of cancers in the supplemented group.

                                           Gina Kolata of The New York Times wrote a feature on vitamin D back in April of this year highlighting the recommendation to use a cutoff of 30 nanograms per mil to define low vitamin D status has resulted in large numbers of individuals being designated as vitamin D deficient. While levels below 30 nanograms per mil have previously been shown to be associated with diverse adverse health outcomes, causal inference, or evidence for a protective effect of supplementation, remains lacking. Particularly in light of the recent clinical trials showing null effects of vitamin D supplementation, the benefits of increasing serum 25-hydroxy vitamin D through supplementation remain unclear.

                                           There may be an important role for genetics in dissecting the link between vitamin D and outcomes. As reviewed in the British Journal of Cancer in March of this year by Peter Vaughan-Shaw and Lina Zgaga, genetic polymorphisms affecting vitamin D metabolism are associated with cancer outcomes. It is possible that vitamin D supplementation may have a protective effect only in individuals with a particular genotype. However, this remains to be tested.

                                           However, what none of these studies manages to resolve is whether sun exposure itself has any benefits. Perhaps there is something specific about the process of making vitamin D directly from UV exposure that confers protection. Or, perhaps there are other benefits of direct exposure to sunlight independent of the vitamin D synthetic pathway that we do not yet fully understand. Either way, enjoying a little time in the sun this summer may have some benefits, unless you get sunburned. So, please take advice from the dermatologists and avoid prolonged exposure, seek shade from the midday sun, cover up, and use sunscreen.

              Thanks for listening to this bite-sized episode. As always, the links to the papers featured in this episode are posted on We'll be back with more next month.