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Should people at high risk for vitamin D deficiency wait 5 years -Feb 2013

Vitamin D Deficiency: Awaiting Final Proof?

From the Department of Internal Medi
Dr. Peiris is chief of endocrinology at Mountain Home VAMC, Mountain Home, TN, and professor of medicine at East Tennessee State University (ETSU), Johnson City, TN. Dr. Youssef is assistant professor of medicine in the ETSU Division of Infectious Diseases. Drs. George and Khazrik are with the Departments of Internal Medicine at Mountain Home VAMC and ETSU.
This material is the result of works supported with resources and the use of facilities at the Mountain Home VAMC.
The contents of this report do not reflect the position of the U.S. Government or the Department of Veterans Affairs.
For reprints, contact Dr. Peiris at Medicine Service 111, Mountain Home VAMC, Mountain Home, TN 37684; phone: 423439-6368; fax: 423-439-6387; email: alan.peiris at va.gov.

Tennessee Medicine + www.tnmed.org + FEBRUARY 2013

Republished with the permission of the Tennessee Medical Association and Tennessee Medicine, ©2013.”

By Jacob George, MD; Hakam Khazrik, MD; DimaA. Youssef, MD; and Alan N. Peiris, MD (Lon), PhD, FRCP (Lon)

Vitamin D deficiency is a common disease, associated with multiple adverse outcomes. The endocrine effects of vitamin D are well recognized; the autocrine and paracrine effects of this steroid hormone are less well appreciated. These functions include antimicrobial and immune-modulation effects, as well as benefits on cardiovascular health, autoimmune disease, cancer and metabolism. Vitamin D deficiency increases mortality and even a modest amount of vitamin D may enhance longevity.1

Vitamin D deficiency is particularly troubling in ethnic minorities and obese and institutionalized individuals. While the number of publications on vitamin D deficiency has increased exponentially in the last few years, the findings have apparently been polarized into two beliefs. First, espoused by the Institute of Medicine, is the belief that vitamin D deficiency is overhyped and very modest replacement with 600 units per day is adequate to meet nutritional needs.2 The second is the belief that vitamin D deficiency is present to a significant extent in the United States and the global population, and that it needs replacement with doses higher than previously used.3 The recently updated Endocrine Society recommendations about vitamin D intake encouraged the use of 1000 to 2000 international units (IU) as an initial daily dose. There is evidence that vitamin D3 doses under 10000 units daily are safe.

Many healthcare providers are waiting for the final proof, which is customarily interpreted as randomized double-blind placebo-controlled long-term trials. Some pending studies may address these issues but the results will not be known for four to five years. Moreover, the ongoing VITAL study uses only 2000 IU of vitamin D3, which is likely insufficient in obese and minority patients. An alternate viewpoint using the Bradford Hill criteria for causality espoused by W.B. Grant4 weighs the evidence on the basis of temporal relationship, strength of association, dose response relationship, consistency, plausibility and consideration of alternate explanation coherence. Since vitamin D meets many of these criteria as an eti-ologic factor in many chronic diseases, it appears prudent to provide at least a replacement of 1000-2000 units per day pending the "final proof of long-term randomized studies. Grant, et al., have proposed that such an approach may reduce mortality.5 It is likely that this initial dose will need modification based on follow-up testing, since the vitamin D dose response curve shows a wide distribution. Since individual customization of vitamin D dosage will likely be needed, ongoing studies using a fixed dose regimen may result in vitamin D adequacy in some, but not in all, study subjects.

In Tennessee, many counties such as Hawkins County have extremely poor health outcome parameters. Rural citizens are more likely vitamin D deficient and that may contribute to adverse health outcomes.6 Waiting four to five years before adequately treating prevalent vitamin D deficiency is not a viable option. As such, we believe that when the risk-benefit ratio of available data is considered, all individuals should be considered for replacement with 1000-2000 units of vitamin D3 daily with appropriate monitoring to ensure desired vitamin D status.


I. Autier P, Gandini S: Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 167:1730-1737, 2007.
2. RossAC,MansonJE,AbramsSA,etal.:The2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53-58,2011.
3. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al.: Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911-30,2011,
4. Grant WB: How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer?: An examination using Hill's criteria for causality. Dermatoendocrinol 1:17-24, 2009.
5. Grant WB, Boucher WB: Requirements for Vitamin D across the life span. Biol Res Nurs 13:120-133, 2011.
6. Bailey BA, Manning T, Peiris AN: Vitamin D and medical costs in veterans: The impact of living in rural and urban areas. J RuralHlth, 28(4):356-63,2012.

See also VitaminDWiki