Vitamin D deficiency and falls: There's smoke, but is there fire?
Joseph H. Friedman, MD joseph_friedman@brown.edu
From the Department of Neurology, Alpert Medical School of Brown University, Providence, RI.
Neurology. 2011 May 10;76(19):1612-3. Epub 2011 Apr 6.
Houston Merritt, MD, used to say that when one medicine was used in a wide variety of different diseases, it probably did not work for any of them. It is hard not to be equally skeptical about the importance of vitamin D in nonskeletal disorders when it is imputed to be helpful not only for bone-specific diseases such as rickets and osteomalacia, which are associated with vitamin D deficiency, but for diverse syndromes, such as falling, weakness, or cancer, which are themselves of diverse origins.1,–,4 Compounding this skepticism are the numbers of studies and meta-analyses producing conflicting results on the benefits of supplementing vitamin D and calcium in deficient and nondeficient people.
There is no gainsaying the fact that vitamin D is important to humans at all ages. The bone diseases of rickets, in children, and osteomalacia, in adults, are well known disorders of vitamin D deficiency. Vitamin D deficiency or hypocalcemia in children causes abnormal mineralization of the growth plates in the long bones, with secondary bone deformities. Osteomalacia is caused by vitamin D deficiency in adults causing abnormal bone mineralization, resulting in bone pain away from the joints, often with proximal muscle weakness and gait abnormalities. However, while vitamin D deficiency is required for osteomalacia to develop, it is not sufficient.1
Vitamin D deficiency has been associated with at least the following syndromes: cancer, cardiovascular diseases, hypertension, diabetes, metabolic syndrome, immune disorders, falls, “physical performance,” preeclampsia, reproductive outcomes, cognitive impairment, muscle weakness, depression, schizophrenia, Alzheimer disease, multiple sclerosis, and autism.1,–,4 There are rationales and data to support each assertion. Yet even if vitamin D deficiency may play a contributing role in the development of these conditions, it is equally true that vitamin D supplementation has not clearly been shown to improve any of these. The December 2010 Institute of Medicine (IOM) report3 on dietary calcium and vitamin D concludes that data “support a role for vitamin D and calcium in bone health but not in other health conditions,” and cautions against ingesting vitamin D in excess.
In this issue of Neurology®, a large and excellent observational study of 411 community-dwelling older people correlated a number of measures primarily related to gait with serum levels of 25-hydroxyvitamin D, a standard measure of circulating vitamin D. Simple memory and strength testing were also included as well as historical data on falls.5 Subjects were categorized into 3 groups: vitamin D severely deficient, vitamin D insufficient, and vitamin D normal, based on generally recognized serum levels of 25 hydroxyvitamin D. The primary correlation target was the stride time variability (STV), a statistical measure of the variability in time spent from stride to stride during “steady state walking” in a 4-meter-long corridor. STV provides an objective, reproducible measure of fall risk, which might be a more sensitive marker for fall risk than the actual number of remembered falls. It has the advantage of producing a far higher power for statistical significance, as most subjects did not fall, and there is no recall problem. However, one must be cautious about confusing the marker and the disease itself, a general limitation of surrogate measures. The central hypothesis, that low vitamin D would correlate with increased STV, the proxy for gait instability, was borne out.
Yet there were no significant differences in actual falls among the 3 groups. And there were no differences in strength, which was, unfortunately, measured in the hands rather than the legs. Indeed, the literature is divided on whether vitamin D supplementation prevents falls. Two recent meta-analyses found vitamin D supplements to reduce falls 6,7 while a Cochrane Review 8 and the IOM report 3 did not. A recent double-blind placebo-controlled study 9 in which older women were given a whole year's worth dose of vitamin D once yearly for 3 years, to guarantee compliance, found that, despite elevated levels of vitamin D over the following year, the frequency of falls and fractures had both increased, and that the highest risk of falling, which was in the first 3 months, correlated with the highest serum level of the vitamin. Thus, while the observations about STV are interesting, the practical consequences of vitamin D serum levels on falling remain unclear.
Furthermore, we do not know much about the general health status of the subjects in the current report. General health is particularly important here because vitamin D serum levels reflect not only diet, but sunlight exposure and obesity. Vitamin D is stored in fat so that obese people have lower serum levels of vitamin D than thin people, and since vitamin D increases dramatically with sun exposure, those who do not spend time outdoors will have lower levels than those who do. This raises the chicken and egg question. Are low vitamin D levels and elevated STV both epiphenomena due to lack of outdoor exercise, obesity, or other unmeasured parameters? Given vitamin D's many apparent effects on non-neurologic health, just how specific are its effects on gait?
To deconstruct the issue even more, perhaps gait should be considered more generally as a proxy for frailty.10 If higher vitamin D serum levels are protective against frailty, perhaps there is a role for vitamin D supplementation. There may be subpopulations which do benefit. Yet vitamin D deficiency is so widespread4 that proving a treatment effect for vitamin D intervention will require large, highly selected populations. Perhaps the work of Beauchet et al.5 should be viewed from the perspective of reduction in frailty rather than reduction of falling.
DISCLOSURE
Dr. Friedman served on scientific advisory boards or as a consultant for Teva Pharmaceutical Industries Ltd., EMD Serono, Inc., ACADIA Pharmaceuticals, and Genzyme Corporation; has received funding for travel or speaker honoraria from Teva Pharmaceutical Industries Ltd., Boehringer Ingelheim, GlaxoSmithKline, and United Biosource Corporation; serves as Editor-in-Chief of Medicine & Health/Rhode Island and on the editorial boards of Parkinsonism & Related Disorders and Neurology Reviews; receives publishing royalties for Making the Connection Between Brain and Behavior: Coping with Parkinson's Disease (Demos Health, 2007); serves on speakers' bureaus for Teva Pharmaceutical Industries Ltd., GlaxoSmithKline, and Boehringer Ingelheim; and receives research support from Teva Pharmaceutical Industries Ltd., Boehringer Ingelheim, Cephalon, Inc., ACADIA Pharmaceuticals, the NIH, and the Michael J. Fox Foundation.
Copyright © 2011 by AAN Enterprises, Inc.
REFERENCES
1.?
Thacher TD,
Clarke BL
. Vitamin D insufficiency. Mayo Clin Proc 2011; 86:50–60.
Abstract/FREE Full Text
2.?
Nimitphong H,
Holick MF
. Vitamin D, neurocognitive functioning and immunocompetence. Curr Opin Nutr Metab Care 2011; 14:7–14.
3.?
Institute of Medicine. Dietary reference intakes for calcium and vitamin D: Washington, DC, December 15, 2010. Available at: www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. Accessed February 2011.
4.?
Rosen CJ
. Vitamin D insufficiency. N Engl J Med 2011; 364:248–254.
CrossRefMedline
5.?
Beauchet O,
Annweiler C,
Verghese J,
Fantino B,
Herrmann FR,
Allali G
. Biology of gait control: vitamin D involvement. Neurology 2011; 76:1617–1622.
Abstract/FREE Full Text
6.?
Kalyoni RR,
Stein B,
Valiyil R,
et al
. Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. J Am Gerontol Soc 2010; 58:1299–1310.
CrossRefMedline
7.?
Michael YL,
Whitlock EP,
Lin JS,
et al
. Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the US Preventive Services Task Force. Ann Int Med 2010; 153:815–825.
Abstract/FREE Full Text
8.?
Gillespie LD,
Robertson MC,
Gillespie WJ,
et al
. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009; 2: CD007146.
9.?
Sanders KM,
Stuart AL,
Williamson EJ,
et al
. Annual high dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010; 303:1815–1822.
Abstract/FREE Full Text
10.?
Fried LP,
Tangen CM,
Walston J,
et al.
,Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56:M146–M156.
Abstract/FREE Full Text
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See also VitaminDWiki