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Electronic letters published:
![[Read Comment]](/icons/misc/sectionDOWN.gif){kind=icon}
Role of Vitamin D in Racial Disparities in Health
Vitamin D and Health Disparities
Contradiction between observational and randomized trials
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Kevin Fiscella, Rochester, NY USA Family Physician, University of Rochester
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Both Drs Gouni-Berthold and Fuller raise critical questions that have enormous implications for addressing health disparities. Dr Gouni-Berthold raises the issue of dose. Available research shows that doses shown to be ineffective in improving cardiovascular outcomes are too low to attain optimal serum levels of vitamin D, particularly among African Americans.(1) Whether high doses improve cardiovascular outcomes in older persons will be addressed through a large, randomized controlled trial that is starting (www.VitalStudy.org) in which participants will receive 2,000 IU vitamin D as one of the arms of the study. Dr Fuller's comments raise a more troubling question that will not be easily addressed. She correctly notes that African Americans have much higher rates of vitamin D deficiency across the entire life course than whites(2-4) and suggests as others have that currently recommended supplements are inadequate. There is growing observational data supporting Dr Fuller's hypothesis that vitamin D deficiency represents a significant contributor to Black- White health disparities, extending beyond cardiovascular disease to include other conditions. Most of the conditions that have been associated with vitamin D deficiency also are more prevalent among African Americans. Examples include pre-eclampsia, asthma, diabetes, hypertension, kidney disease, and cancer, particularly colorectal cancer.(5;6) Low levels may even predict having a Cesarean section.(7) The consequences of deficiency beginning in-utero are not fully known, but potentially substantial. Vitamin D is not a true a vitamin, but a pro hormone that directly or indirectly regulates over 200 genes. It is not known whether potential developmental effects from early vitamin D deficiency would be reversed by high doses given late in life. The American Academy of Pediatrics increased its recommended intake for infants, children, and adolescents to 400 IU vitamin D per day in effort to address the problem. While this amount will prevent rickets, it will not be enough to achieve presumed optimal levels for much of the population, particularly African Americans. Resolving the question of the optimal dose of vitamin D for pregnant women, infants, children, and adults will be challenging, but the stakes are high, particularly for addressing health disparities. An Institute of Medicine report on recommended vitamin D intake is expected out this year. (1) Talwar SA, Aloia JF, Pollack S, Yeh JK. Dose response to vitamin
D supplementation among postmenopausal African American women. Am J Clin
Nutr 2007; 86(6):1657-1662.
Competing interests: None declared |
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Kathleen E Fuller, Kansas City, USA Director, AnthroHealth
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I am very pleased to see the publication of this research by Fiscella and Franks which tied the higher incidence of cardiac disease among the African-American population to vitamin D deprivation. It has been over 16 years since I first began researching (and later writing) about the issue of health disparities and the probable relationship to vitamin D deprivation. Unlike many other causes postulated for health disparities, vitamin D deprivation is something that is relatively easy to remedy through supplementation with vitamin D3 tablets/pills. The amount needed to raise an individual’s level of 25 OHD to at least 40ng/mL is certainly much higher than the current DRIs. This is especially true for individuals with moderate-to-heavy degrees of pigmentation who will be unable to optimize their 25 OHD levels through UVB radiation exposure. Therefore, it is not surprising that studies using low levels of supplementation have shown mixed results. Life-long vitamin D deprivation (from birth onwards) is probable among a significant percentage of the African-American population. This deprivation will not easily be overcome by a supplementation of 200, 400, 800, or even 1000 IU/day of D3. If the healthcare community really cares about eradicating health disparities, there is no better place to begin than with adequate vitamin D supplementation for all individuals. What is adequate supplementation for a heavily-pigmented individual who surely began life with suboptimal levels of 25 OHD will be quite different from that of a very lightly-pigmented individual who may need supplementation of only a few hundred IU/day. For too long supplementation recommendations have operated under a “one-size-fits-all” policy. This must change if real progress towards eradicating health disparities is to be made. Kathleen E. Fuller, PhD, Director, AnthroHealth (Kansas City, USA) 1. Fuller, K. Health Disparities: Reframing the Problem. Medical Science Monitor 2003 9 (3): SR9-15. 2. Fuller, K. & Casparian, J.M. Vitamin D: Balancing Cutaneous and Systemic Considerations. Southern Medical Journal 2001 94 (1): 58-66. 3. Fuller, K. Low-Birth-Weight Infants: The Continuing Ethnic Disparity and the Interaction of Biology and Environment. Ethnicity and Disease 2000 10: 432-445. 4. Fuller, K. The African-American Fertility Decline: 1880-1940: UVB Radiation Deprivation as a Contributory Factor. 1998 Dissertation. University of Kansas. 5. Fuller, K. Pelvic Differences Between African-American and European-American Females and the Link to Rickets. American Journal of Physical Anthropology April 1997 Supl. 24: 114. Competing interests: None declared |
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Ioanna Gouni-Berthold, Cologne, Germany Professor of Internal Medicine and Endocrinology, Dept. of Internal Medicine II, Univ. of Cologne, Heiner K. Berthold
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Accumulating evidence suggests that vitamin D status may be an important determinant of cardiovascular disease (CVD) risk (reviewed in 1). The study of Fiscella and Franks is the latest in a recent series of non-randomized trials, showing an association between low vitamin D levels and cardiovascular mortality (2, 3) and further suggests that the increased CVD risk observed in blacks may be partially due to the lower vitamin D levels observed in this population. However, no randomized controlled trial (RCT) to date has been able to show that vitamin D supplementation lowers CVD risk. Two RCTs reported on vitamin D administration and CVD mortality. The first was performed in the United Kingdom, where 2686 subjects aged 65 to 85 years were randomized to either 830 IU/day vitamin D or placebo for 5 years (4). There was a 16% non-significant decrease in CVD mortality in the intervention group (RR of 0.84; 95% CI 0.65 to 1.10). The second was the Women’s Health Initiative (5), in which 36,282 postmenopausal women were assigned to either vitamin D (400 IU/day) and calcium (1000 mg/day) or placebo. No reduction in the CVD mortality was observed (HR 1.04; 95% CI 0.92 to 1.18). Therefore, the results of the RCTs seem to contradict the ones of the non-randomized trials. Two possible explanations for this phenomenon could be postulated. First, the associations in the observational studies may have been confounded and second, the vitamin D doses used may simply have been too low. Current recommendations for vitamin D intake vary among countries and among the indications targeted, but are generally in the range of 200 to 600 IU/day. These doses are now being reconsidered since the average levels of vitamin D in Europe are 18 ng/ml and a dose of approx. 2000 IU/day is needed in order to raise circulating 25(OH)vitamin D levels by 15 ng/ml (adequate vitamin D levels are 40 to 100 ng/ml). While awaiting definitive evidence from RCTs, it seems prudent to recommend vitamin D supplementation to our patients in order to achieve a plasma level of at least 30 ng/ml, the level above which CVD risk is minimized in most of the trials. Ioanna Gouni-Berthold, MD, Dept. of Internal Medicine II, University of Cologne (Germany) Heiner K. Berthold, MD, PhD, Dept. of Geriatrics, Charité University Medicine Berlin (Germany) References: 1. Gouni-Berthold I, Krone W, Berthold HK. Vitamin D and cardiovascular disease. Curr Vasc Pharmacol 2009 July;7(3):414-22. 2. Semba RD, Houston DK, Bandinelli S et al. Relationship of 25- hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr 2009 December 2;epub ahead of print. 3. Kilkkinen A, Knekt P, Aro A et al. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol 2009 October 15;170(8):1032-9. 4. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003 March 1;326(7387):469. 5. Hsia J, Heiss G, Ren H et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007 February 20;115(7):846-54. Competing interests: None declared |
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