On the Possible Link Between Vitamin D Deficiency and Cardiovascular Disease: Should We D-Lighten Our Lives? Pelle G. Lindqvist Circulation. 2014;129:e413-e414 doi: 10.1161/CIRCULATIONAHA.113.004489 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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Cardiology Patient Page

On the Possible Link Between Vitamin D Deficiency and Cardiovascular Disease Should We D-Lighten Our Lives? Pelle G. Lindqvist, MD, PhD

W

e were all supposedly black in the beginning. As man migrated out from the equator, a progressive depigmentation took place. For this to occur, strong evolutionary forces in favor of less pigmentation must have been present in regions with low solar exposure. We do not know toward what end such an advantage might have been working, but a main hypothesis is that in regions with low sun ultraviolet (UV) radiation, less pigmented individuals would need less time in the sun to avoid vitamin D deficiency. This, in turn, might have helped avoid respiratory tract infections, tuberculosis, and influenza—conditions that have proven lethal over the course of time.1 Because, in most populations, females have less pigmented skin and approximately twice the risk of vitamin D deficiency as males, female reproduction may be involved in an evolutionary advantage, that is, improved fertility, fewer miscarriages, or fewer pregnancy complications. Even a small increase in successful reproduction per generation will make a great difference in the

long run, favoring skin pigmentation adapted to a particular region.

Lower Risk of Excess Mortality Individuals with heart failure, hypertension, stroke, and other cardiovascular diseases (CVD) tend to have lower vitamin D levels than others.2 In addition, manifestations of CVD are more common during the winter season, when vitamin D levels are at their lowest. Incidental type 2 diabetes mellitus is more prevalent among people with low vitamin D levels or those who avoid sun exposure.3 Hemoglobin A1c, a marker of glucose levels, also shows a cyclic appearance, dropping to its lowest levels in the summer. In addition, there is an inverse relationship between vitamin D levels and hypertension, obesity, and waist circumference. However, these findings show associations that are not necessarily causal. The fact that hypertension improves with UVB (but not UVA) radiation, that vitamin D supplementation (800 U/d) lowers incidental type 2 diabetes mellitus, and

that newborns who receive vitamin D supplementation are at a 80% lower long-term risk of childhood or adolescent diabetes mellitus adds to causality. However, the results are inconsistent, possibly owing to differences in dosage. Dosage often tends to be low (400 U/d), whereas higher doses are needed to avoid vitamin D deficiency (2000– 4000 U), and longer treatment periods appear to be necessary.1 In addition, differences in the vitamin D status of the populations being studied presumably matter; increasing vitamin D levels in populations with a low prevalence of vitamin D deficiency is unlikely to improve health. A Swedish study showed that people who go for sunbathing vacations at least once a year during 3 decades had lower CVD and all-cause mortality.4

How Can One Safely Avoid Vitamin D Deficiency in Regions With Low UV Radiation? Although we know that people who eat more fish and eggs tend to have a better

The information contained in this Circulation Cardiology Patient Page is not a substitute for medical advice, and the American Heart Association recommends consultation with your doctor or healthcare professional. From Clintec, Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Sweden. Correspondence to Pelle G Lindqvist, MD, PhD, Department of Obstetrics and Gynecology, Clintec, Karolinska Institute, Karolinska University Hospital, Huddinge, Kvinnokliniken K 57, SE-14186 Stockholm, Sweden. Email [email protected] (Circulation. 2014;129:e413-e414.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org

DOI: 10.1161/CIRCULATIONAHA.113.004489

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vitamin D status than others, food is low in vitamin D content. As the source of vitamin D, food is especially poor for vegans, vegetarians, and those with food intolerances. The body produces the greatest amount of its vitamin D in the skin after exposure to UVB radiation from sunlight. In regions far from the equator like Sweden, most UVB radiation in the morning and late afternoon is filtered through the atmosphere. Thus, short daily exposure to the sun at midday is presumably the best way to obtain robust levels of vitamin D, but one must be careful to avoid sunburn. Pigmented skin acts as a sun shield, and so pale individuals need less time in the sun than more densely pigmented individuals. People who are lean need a shorter time than those who are overweight. Sun protection cream hinders vitamin D production. A common misinterpretation of the current sun exposure guidelines is that, as long as you apply sun block, you can be out in the sun for a long time. This is probably the reason why using sun protection cream is an established risk factor for melanoma, because it results in people staying in the sun too long. There is almost no scientific evidence that sun shields lower the risk of melanoma. The misinterpretation of the current guidelines might be a contributing factor to the increasing incidence of melanoma in some countries. We presently know that sunburn and the use of tanning machines more than 10 to 12 times a year, especially among teenagers, increase the risk of melanomas. This is especially true for those who have (1) red hair, (2) a large number of moles, (3) a tendency toward devel­ rst-degree oping freckles, and (4) a fi relative with melanoma. On the other hand, vitamin D deficiency seems to be related to more aggressive melanomas and increased mortality. Thus, both sun

avoidance and excessive sun exposure are extreme behaviors that threaten our health. We recommend taking a lunch break and after a sufficient time (individual), covering up, or moving into the shade. In regions of more intense UV radiation, less exposure may be advisable.

What Do You Recommend for Individuals at Increased Cardiovascular Risk? Besides the usual recommendations of maintaining normal weight (ideally body mass index=25), not smoking, and exercising for at least 30 minutes per day, I recommend that my patients who are at increased risk of thrombosis avoid vitamin D deficiency either by adopting active sun exposure habits or by using vitamin D supplements. It has been shown that incidental thromboembolic events occur more frequently among those who avoid sun exposure and that the risk is almost doubled during the winter season.5 These recommendations might well be true for all CVDs, although one should remember that the sun exposure and vitamin D supplementation recommendations given here are based on epidemiological, rather than causal, evidence.

Risk Factors for Vitamin D Deficiency Decreased vitamin D production from UV radiation: Covered or colored skin Older adults Overweight individuals Living in a region with low UV radiation Avoiding sun exposure Lower vitamin D uptake from food: Vegans Vegetarians

Gastric surgery Food intolerance Miscellaneous: Female sex The long-standing doctrine that sun exposure can only be discussed in terms of danger from skin cancer is presently being challenged. A more balanced view has begun taking into account not only the incidence of skin cancer, but also the morbidity and mortality from CVD and cancer as well. The next decade may reveal whether a causal relationship between vitamin D/ sun exposure and CVD morbidity and mortality exists.

Disclosure None.

References 1. Bergman P, Norlin AC, Hansen S, Rekha RS, Agerberth B, Björkhem-Bergman L, Ekström L, Lindh JD, Andersson J. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663. 2. Liu L, Chen M, Hankins SR, Nunez AE, Watson RA, Weinstock PJ, Newschaffer CJ, Eisen HJ. Serum 25-hydroxyvitamin D concentration and mortality from heart failure and cardiovascular disease, and premature mortality from all-cause in United States adults. Am J Cardiol. 2012;110:834–839. 3. Lindqvist PG, Olsson H, Landin-Olsson M. Are active sun exposure habits related to lowering risk of type 2 diabetes mellitus in women, a prospective cohort study? Diabetes Res Clin Pract. 2010;90:109–114. 4. Yang L, Lof M, Veierød MB, Sandin S, Adami HO, Weiderpass E. Ultraviolet exposure and mortality among women in Sweden. Cancer Epidemiol Biomarkers Prev. 2011;20:683–690. 5. Lindqvist PG, Epstein E, Olsson H. Does an active sun exposure habit lower the risk of venous thrombotic events? A D-lightful hypothesis. J Thromb Haemost. 2009;7:605–610. Key words: evolution ◼ heart disease ◼ lifestyle ◼ prevention ◼ stroke ◼ thrombosis ◼ vitamin D

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Cardiology Patient Page. On the possible link between vitamin D deficiency and cardiovascular disease: should we D-lighten our lives?

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