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Cardiovascular Disease and vitamin D - April 2012

Can Vitamin D Deficiency Break Your Heart?

LETTERS TO THE EDITOR Mayo Clin Proc. April 2012;87(4):412-415 © 2012 Mayo Foundation for Medical Education and Research

To the Editor:
We congratulate Hoang et al1 from the Cooper Center Longitudinal Study on their article reporting a signifi­cant association between low serum 25-hydroxyvitamin D [25(OH)D] levels and depression among the largest group of in­dividuals in whom this potential link has been explored to date. The fact that this study was done as part of a medical stu­dent summer research program makes it even more impressive. In the same issue of Mayo Clinic Proceedings, Chamberlain et al 2 report that among a cohort of patients with preexisting cardiovascular (CV) dis­ease, depression independently predicted hospitalization and all-cause mortality over a 17-year follow-up period. We have recently documented strong independent associations between low vitamin D levels and adverse CV events,3-5 and some meta-analyses show that vitamin D supplemen­tation appears to significantly lower all-cause mortality,6 whereas others do not.7 Thus, it is biologically plausible that vita­min D deficiency-induced depression may, in part, be responsible for increased CV risk associated with low vitamin D levels. Additionally, the tendency for de­pressed patients to stay indoors and be physically inactive (both risk factors for vitamin D deficiency) may lead to low vitamin D levels, which, in turn, are as­sociated with increased CV risk.2 Al­though the study from Hoang et al 1 dem­onstrates that the association between low 25(OH)D levels was independent of phys­ical activity, we were surprised that these Cooper Center Longitudinal Study data were also not corrected for precisely mea­sured levels of cardiorespiratory fitness.

Vitamin D deficiency, besides being associated with depression, appears to in­crease the risk of developing inflamma­tion, insulin resistance, diabetes, and ath­erosclerosis, and also activates the renin-angiotensin-aldosterone system, which predisposes to hypertension and left ven­tricular hypertrophy.3-5 All of these con­sequences of vitamin D deficiency, includ­ing depression, can adversely affect CV health and longevity (Figure).

FIGURE. Potential mechanisms for CV effects of vitamin D deficiency. CV = cardiovascular; DM = diabetes mellitus; HTN = hypertension; LVH = left ven­tricular hypertrophy; MetS = metabolic syndrome; RAAS = renin-angiotensin-aldosterone system. From J Am Coll Cardiol, 5 with permission.

An abnormally low vitamin D level, as defined by a serum 25(OH)D level less than or equal to 20 ng/mL, is present in 42% of the overall American adult popu­lation, 82% of black individuals, and 69% of the Hispanic population. 3 The average 25(OH)D level in adults is 20 ng/mL 8;a long-term daily intake of an additional 100 IU of vitamin D will increase this level by only about 1 ng/mL. 3-5 Thus, supple­menting the diet by the 600 to 800 IU daily as recommended by the Institute of Medicine's new guidelines 9 would be ex­pected to raise adult Americans' mean vi­tamin D levels to 26 to 28 ng/mL, which is still in the insufficient range (<30 ng/mL). Recently, the Endocrine Society clinical practice guidelines10 suggested doses of 1000 to 2000 IU of vitamin D3 daily, which are much more likely to achieve a 25(OH)D level of at least 30 ng/mL.

Insufficient vitamin D causes muscu-loskeletal pain and weakness, and supple­menting low 25(OH)D levels back into the normal ranges has been shown unequivo­cally to improve integrity and strength of bones and muscles and to reduce falls.4,5 Large randomized controlled trials are un­der way, and these should help to deter­mine whether raising low vitamin D levels will also reduce risks for CV events, de­pression, and death. These results are not expected for several years (at least 3 years and possibly 5 years or more), and in the meanwhile it seems prudent to recom­mend a daily intake of 1500 to 2000 IU of vitamin D3 for most American adults. Re­cent data, including those from Mayo Clinic Proceedings,1,2 suggest that measur­ing vitamin D levels and normalizing defi­ciencies may be especially important for individuals with a history of depression and/or CV disease.

James H. O'Keefe, MD Harshal R. Patil, MD
Saint Luke's Hospital Kansas City, MO
Carl J. Lavie, MD
John Ochsner Heart and Vascular Institute Ochsner Clinical School-The University of Queensland School of Medicine New Orleans, LA
Dr O'Keefe is chief medical officer and founder of CardioTabs, a nutraceutical corporation that has vitamin D products.
(CardioTabs 1300 mg Omega3 and 600 IU of vitamin D)

1. Hoang MT, Defina LF, Willis BL, Leonard DS Weiner MF,Brown ES.Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults:the Cooper Cen­ter Longitudinal Study.Mayo Clin Proc. 2011 36(II):I050-I055. CLICK HERE for paper
2. Chamberlain AM, Vickers KS, Colligan RC Weston SA,Rummans TA,Roger VL.Associations of preexisting depression and anxiety with hospitalization in patients with cardiovascular dis­ease. Mayo Clin Proc. 20II;36(II):I056-I062
3. O'Keefe JH, Lavie CJ, Holick MF. Vitamin D sup­plementation for cardiovascular disease preven­tion. JAMA. 20II;306(I4):I546-I547; author re­ply I547-I543.
4. Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF.Vitamin D deficiency an important,common and easily treatable cardiovascular risk factor? J Am Coll Cardiol. 2003;52(24):I949-I956
5. Lavie CJ, Lee JH, Milani RV. Vitamin D and car­diovascular disease:willit live up to its hype? J Am,Coll Cardiol. 20II;53(I5):I547-I556.
6. Bjelakovic G,Gluud LL,Nikolova D,et al.Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 20II(7) CD007470.
7. Elamin MB, Abu Elnour NO, Elamin KB, et al Vitamin D and cardiovascular outcomes: a sys­tematic review and meta-analysis. JClin Endocrinol Metab. 20II;96(7):I93I-I942.
8. Forrest KY, Stuhldreher WL. Prevalence and cor­relates of vitamin D deficiency in US adults. Nutr Res. 20II;3I(I):43-54.
9. Ross AC, Taylor CL, Yaktine AL, Del Valle HB Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 20II
10. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al Evaluation, treatment, and prevention of vitamin D deficiency:an Endocrine Society clinicalpractice guideline. J Clin Endocrinol Metab. 20II;96(7) I9II-I930.

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