Friday, February 15, 2013

What’s Really In That Vitamin D Pill?

Briefly NotedBecause vitamin D insufficiency can be harmful to health and is suspected as being associated with certain pain conditions, supplementation is often recommended. However, vitamin D products are largely unregulated, so their potency may not be well evaluated and, consequently, many persons may not be benefitting as expected from taking the pills.

United States Pharmacopeial (USP) Convention standards require that contents of over-the-counter (OTC) dietary supplements should be within 90% to 120% of the stated dose, and compounded pills — those custom formulated — should contain 90% to 110% of the active ingredient. However, there can be high variability in the potency of both compounded and OTC cholecalciferol (vitamin D3) supplements, according to new evidence.

Researchers at the Kaiser Permanente Center for Health Research in Portland, Oregon, and Eagle Analytical Services in Houston, Texas, conducted an experiment to accurately assess variability in the potency of OTC and compounded vitamin D3 pills [LeBlanc et al. 2013]. They assayed the potency of multiple vitamin D3 pill samples — 1,000 IU, 5,000 IU, and 10,000 IU — from locally purchased bottles of the supplement produced by 12 different manufacturers, only one of which was a USP-Verified dietary supplement. They also investigated specially compounded vitamin D3 pills — 1,000 IU and 50,000 IU — on several different occasions.

Writing in an early online edition of JAMA Internal Medicine (formerly Archives of Internal Medicine), the researchers report that the vitamin D3 content of both OTC and compounded vitamins was highly variable, with potencies surprisingly ranging from 9% to 146%. Overall, just over one-half of OTC pills and only one-third of compounded pills met USP Convention standards. The researchers note that differences in storage times did not account for potency differences, and the single OTC manufacturer that was USP-Verified was generally more accurate and less variable, as might be expected.

As more people are advised to take vitamin D3 supplements, LeBlanc and colleagues caution that healthcare providers and patients need to understand that cholecalciferol potency may vary widely. Products that are USP-Verified may have better accuracy, but they may not be readily available, and this could be especially problematic outside the U.S. On the basis of this study, the researchers note that they agree with others who have recently called for increased government regulation of dietary supplements.

Vitamin DCLINICAL COMMENT: Potential benefits of vitamin D3 supplementation for a variety of pain conditions have been discussed in various Pain-Topics UPDATES [here] and in our special research reports [available here]. Unfortunately, an often unanswered questions is, “Where can the best and most reliable quality supplements be found?”

In 2007, the U.S. FDA established regulations requiring current Good Manufacturing Practices (cGMP) for dietary supplements. Manufacturers are required to evaluate the identity of ingredients, their strength, and the composition of their products, and to report all product related serious adverse events to the FDA; however, some authorities believe that these requirements need more rigid and aggressive enforcement.

The US Pharmacopeia [] has a program for assessing the strength, purity, and quality of dietary supplements, and awards its “USP-Verified” label to those that are accepted. Similarly, NSF International [], a worldwide nonprofit, non-government organization, awards its “Certification Mark” to products that comply with its rigorous standards of quality. Relatively few supplement manufacturers seek such certifications, but those that do qualify can be found listed at the USP and NSF websites (with some searching).

The lack of accuracy in the vitamin D3 content of many OTC products may not cause serious harm in most consumers; however, it also means that many persons may not realize the potential benefits of such supplementation. And, especially in patients with pain and/or vitamin D deficiencies, supplementation may be less effective and dose adjustments inaccurate due to poor-quality products. In such cases, laboratory assessment of serum vitamin D, as the 25(OH)D metabolite, may be the only way of knowing if supplementation is adequate to achieve desired effects.

It is somewhat surprising that compounded versions of vitamin D3 also were of variable potency. This unpredictability may threaten the validity of vitamin D research trials that use compounded pills presumed to be of specific and consistent potency. It is something to consider as a confounding factor when trial outcomes do not measure up to expectations.

REFERENCE: LeBlanc ES, Perrin N, Johnson JD, et al. Over-the-Counter and Compounded Vitamin D: Is Potency What We Expect? JAMA Intern Med. 2013; online ahead of print [abstract here].

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