To D or Not to D?
Abstract & Commentary
By Allan J. Wilke, MD, MA
Professor and Chair, Program Director, Department of Family Medicine, Western Michigan University School of Medicine, Kalamazoo
Dr. Wilke reports no financial relationships relevant to this field of study.
Synopsis: The American Geriatrics Society has published guidelines on the use of vitamin D supplementation for the prevention of falls in the elderly, but some researchers are not on board with this.
Source: American Geriatrics Society workgroup on vitamin D supplementation for older adults. Recommendations abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc 2013; Dec. 18.
doi: 10.1111/jgs.12631. [Epub ahead of print].
This summary condenses the efforts of the american geriatrics Society (AGS) workgroup on vitamin D supplementation for the elderly into what the workgroup imagined would be bite-size, digestible nuggets for primary care providers (PCPs). It is a very dense report. The entire 38-page document is available for sale.1 [Disclaimer: I am a member of AGS, but did not have a hand in the development of these guidelines.]
The recommendations begin with a brief review of how vitamin D is made. It is synthesized in the skin by way of exposure of cholesterol to ultraviolet B light, hydroxylated in the liver to 25-hydroxyvitamin D [25(OH)D], and then hydroxylated again to 1,25-dihydroxyvitamin D (D3). We get our vitamin D through sun exposure, by way of supplements, and through eating foods that are fortified with vitamin D.
The overall goal of the recommendations is to reduce injuries from falls attributable to low serum vitamin D levels. To achieve that goal, the workgroup reviewed the literature through 2010 and formulated six objectives:
• Develop clinical guidelines that address vitamin D intake from all sources.
• Set goals for 25(OH)D levels that correlate with reduced risk of falls and injuries, while avoiding toxicity.
• Strategize on how to obtain those levels.
• Develop clear guidelines for PCPs.
• Define at-risk groups of the elderly.
• Rate the various ways vitamin D levels are measured.
The recommendations are as follows: Every community dwelling senior (i.e., ≥ 65 years) and institutionalized older adults should be supplemented with at least 1000 international units (IU) daily. This should always be coupled with calcium (Ca++) supplementation; however, the workgroup did not specify an amount of Ca++. It did note that vitamin D doses < 600 IU do not prevent falls, and Ca++ doses in the studies reviewed were commonly 1000-1200 mg daily. Supplementation of an institutionalized older adult should be with a dose of vitamin D ≥ 1000 IU/d, plus Ca++.
Serum 25(OH)D levels should be > 30 ng/mL (75 nmol/L). The best way to achieve this is by reviewing all sources of vitamin D and keeping the total at 4000 IU. The authors include a table for individualizing the dose based on food intake, multivitamin use, unprotected sun exposure, obesity, and skin pigmentation. Individuals taking medications that bind vitamin D or increase its metabolism or have malabsorption syndromes may need their doses tweaked.
Routine measurement of 25(OH)D serum levels isn’t necessary before beginning supplementation, nor after for monitoring, unless you are outside the recommended dose. If you decide to monitor anyway, wait until 4 months and measure at the midpoint between doses. You might want to monitor the people who show up in the table.
Vitamin D is available as ergocalciferol (D2) by prescription and cholecalciferol (D3) over-the-counter, and either form may be used. Vitamin D3 is derived from animal sources, possibly a problem for vegetarians. They differ in their pharmacokinetics; the maximal dosing interval for vitamin D2 is 2 weeks and vitamin D3 is 4 months. Because of its long dosing interval, vitamin D3 can be given daily, weekly, or monthly.
There were a number of warnings and "don’t do this" statements. Don’t prescribe once-yearly doses of either to get a patient through the winter. Don’t use combination vitamin D/Ca++ tablets as the primary source of vitamin D, because the doses of vitamin D are too small and the tablets need to be dosed daily. The combination of a daily vitamin D/Ca++ tablet and a monthly vitamin D capsule may be a good compromise. Don’t rely on cod liver oil, because of the risk of vitamin A toxicity at the dose needed for adequate vitamin D. Taking vitamin D with meals that contain oil is good; taking vitamin D with cholestyramine and high-fiber foods or supplements is not.
One thing I like about these recommendations is that the goal was outcome-based (preventing injuries), rather than biochemically-based. However, before adopting these guidelines, please read the following.
Things got a little murky in late 2013 and last month with the publication of four systematic reviews/meta-analyses and one study. Powe and colleagues’ study noted the paradox of black Americans consistently having lower levels of total 25(OH)D than whites, while having higher bone mineral density (BMD) and a lower risk of fragility fractures.2 These researchers measured levels of total 25(OH)D, vitamin D-binding protein, the parathyroid hormone, and BMD. They discovered that the average levels of both total 25(OH)D and vitamin D-binding protein were lower in blacks than in whites and concluded that the bioavailable vitamin D are similar. This study was followed by a systematic review of articles that measured the effect of 25(OH)D concentrations on non-skeletal health outcomes in adults.3 The authors concluded, "Supplementation in elderly people (mainly women) with 20 μg [note: equivalent to 800 IU] vitamin D per day seemed to slightly reduce all-cause mortality," and speculated that low levels of vitamin D were not the cause of illness, but the result of inflammatory processes and a marker of illness.
Then, in April, came three articles. In the first two, published in BMJ on April 1, both systematic reviews and meta-analyses, Chowdhury et al concluded that vitamin D3 (but not vitamin D2, which may make things worse) supplementation "significantly reduces overall mortality among older adults," but cautioned against widespread supplementation.4 Theodoratou et al concluded that there is no highly convincing evidence of a clear role of vitamin D for any outcome.5 I do not think that BMJ publishes an April Fools’ edition. You could argue that these two meta-analyses took on the very broad effects of vitamin D on health in general, and the AGS guidelines are focused on preventing falls in the elderly. You could argue that, except for the most recent April article, a trial sequential analysis by Bolland et al6 which asserts that vitamin D does not reduce falls by 15% or more (the risk reduction threshold they set before they conducted the analysis) and thus, there is little reason to prescribe vitamin D.
This is exasperating! My advice? First, do no harm. If you want to prescribe vitamin D, follow the AGS’s guidelines and avoid poisoning your patients. Use vitamin D3 because it’s cheap, it may be safer than vitamin D2, and you can space out the doses. If you don’t want to, you have several meta-analyses to back you up.
- http://geriatricscareonline.org/ProductAbstract/american-geriatrics-society-consensus-statement-vitamin-d-for-prevention-of-falls-and-their-consequences-in-older-adults/CL009. Accessed May 6, 2014.
- Powe CE, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans.
N Engl J Med 2013;369:1991-2000.
- Autier P, et al. Vitamin D status and ill health: A systematic review. Lancet Diabetes Endocrinol 2014;2: 76-89.
- Chowdhury R, et al. Vitamin D and risk of cause specific death: Systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ 2014;348:g1903. doi: 10.1136/bmj.g1903.
- Theodoratou E, et al. Vitamin D and multiple health outcomes: Umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 2014;348:g2035. doi: 10.1136/bmj.g2035.
- Bolland MJ, et al. Vitamin D supplementation and falls: A trial sequential meta-analysis. Lancet Diabetes Endocrinol 2014; Apr 24. doi:10.1016/S2213-8587(14)70068-3.