The ever-increasing numbers of unregulated products from the dietary supplement industry have considerable potential to complicate safe and effective pain care, as well as causing health problems of their own. Clinicians and patients need to be wary of possible consequences posed by the seemingly innocuous supplements that line pharmacy and retail store shelves and fill the pages of countless websites on the Internet.
Writing in a recent edition of the Archives of Internal Medicine, Donald Marcus, MD, and Arthur Grollman, MD, comment that enactment in the United States of the Dietary Supplement Health and Education Act (DSHEA) in 1994 expanded the category of dietary supplements beyond products for treating nutritional deficiencies — such as vitamins and minerals — to include a wide range of botanicals and “other traditional medicinal products” [Marcus and Grollman 2012]. Thereby, such products were excluded from effective regulation by the U.S. Food and Drug Administration (FDA).
The authors note that, under DSHEA, “manufacturers of dietary supplements are not required to provide premarketing evidence of safety or efficacy or, prior to 2007, to report adverse events.” Consequently, sales of supplements proliferated, with consumers spending nearly $15 billion in 2007 alone for nonvitamin-nonmineral products, such as herbals. Between enactment of the DSHEA in 1994 and 2008 the number of dietary supplements on the market rocketed from 4,000 to approximately 75,000.
Along with increasing supplement consumption, reports of serious adverse events and product adulteration also increased. For example, during 2008 the FDA received nearly 600 reports of serious adverse events and 350 voluntary reports of moderate or mild adverse events. However, the authors state, “the FDA believes that adverse events are significantly underreported and estimates that the annual number of all adverse events [related to supplements] is 50,000.”
Even when the FDA identifies an unsafe product, the agency lacks authority to mandate its removal from the market unless the product meets the very high legal requirement of “significant or unreasonable” risk. “That is why it took the FDA more than 10 years to remove from the market ephedra-containing herbal weight-loss products that had caused hundreds of deaths and thousands of adverse events,” Marcus and Grollman suggest.
Additionally, the authors continue, the labeling of dietary supplements often is inadequate and consumers are poorly informed about the products and their potential to cause adverse effects. There also is a lack of regulation regarding health claims made by manufacturers. Investigations have revealed that promotional websites frequently make unsound and illegal claims that the dietary supplements will cure or prevent serious diseases or conditions. And, in one probe, investigators posing as customers at retail outlets were told by sales staff that herbal supplements not only were safe but could be taken instead of prescription medicines.
The FDA does periodically issue warnings to consumers concerning the dangers of adulterated dietary supplements that can cause serious adverse events. Marcus and Grollman observe that such alerts have been issued for nearly 300 products; however, the European Union (EU) has taken a more active role than the U.S. to ensure the safety and quality of herbal medicines. The Traditional Herbal Medicinal Products Directive of 2004 established a regulatory process requiring that herbal medicinal products must have authorization for marketing in the EU. This requires manufacturers to provide evidence of product safety and scientific support for health claims.
In summary, Marcus and Grollman contend that “the consequences of DSHEA for consumers include the expenditure of tens of billions of dollars annually on ineffective and potentially dangerous dietary supplements.” Healthcare providers have not paid sufficient attention to problems that may affect the 18% of the population that regularly uses nonvitamin, nonmineral dietary supplements.
COMMENTARY: Caveat Emptor, Caveat Medicus
We have previously written (and warned) about dietary or nutritional supplements in Pain-Topics UPDATES [here] and [here]. In their article, Marcus and Grollman were not specifically addressing concerns about the many untested and unproven supplements plaguing the pain-care field, but their message was applicable. As they observe…
“Claims for the efficacy of botanical products made by manufacturers and advocates of complementary and alternative medicine are based on their long history of use and an unscientific distinction between ‘natural’ and synthetic medications rather than on sound scientific evidence. Rigorous controlled trials of popular herbals supported by the National Institutes of Health and other independent sources of funding have found most botanical supplements to be ineffective.”
An internet search on the terms “herbal pain remedy” produces a vast and confusing array of products offering “natural” and “holistic” relief of pain. Most of the information on supplements available in the media and on the Internet is misleading: it overstates product efficacy and minimizes potential toxic effects. Unfortunately, the products are almost always self-prescribed and purchased by patients who are unable to make truly informed decisions about their use or safety.
Of great concern is the potential for dietary supplements to interfere with effective pain management or, worse, to cause drug-drug interactions — ie, various prescribed and nonprescribed agents fighting against each other — leading to serious adverse events [discussed in UPDATE here]. For example, earlier this month [here] we reported on warnings from the FDA regarding the Mexican supplement Reumofan-Plus, sold for pain relief and as a treatment for arthritis as well as other conditions.
Among other ingredients not even listed on the label, Reumofan was found to contain diclofenac — an NSAID that may cause gastrointestinal problems — and methocarbamol — a muscle relaxant that can cause dizziness, low blood pressure, or enough sedation to produce mental or physical impairment. One can imagine how such a product might confuse and confound the status of a patient being treated for pain, when unexpected clinical responses or adverse effects are due to the supplement rather than prescribed medications. Worse yet, past surveys have found that patients often do not inform their healthcare providers of all nonprescribed products they are using for pain.
Even when practitioners know of supplements being taken by patients it poses a dilemma. Marcus and Grollman recommend that healthcare providers should provide guidance to patients about the use of dietary supplements; yet, they also concede that practitioners’ knowledge of this subject often is limited. This is due, in part, to the fact that “education about dietary supplements in many academic institutions is provided by advocates of complementary and alternative medicine in integrative medicine programs” — and such curricula are of poor quality, they believe.
There also are few reliable and authoritative references that practitioners can consult. For example, Marcus and Grollman note that, while the PDR® for Herbal Medicines™ resembles the Physicians' Desk Reference™ for prescription drugs, the latter volume has credible FDA-approved information whereas the former contains largely biased promotional material from manufacturers.
We found that our copy of the PDR herbal volume (©2000) lists nearly 120 agents — from Aga to Yellow Jessamine — in the analgesic category. Few of the descriptions reference any research evidence in support of efficacy and safety, and many of the agents are affected by the same liver enzymes that metabolize some prescription drugs used in pain management, including certain opioid analgesics; so, the potential for drug-drug interactions is evident. Complicating the picture further, commercial supplement preparations almost always combine multiple herbal ingredients making it nearly impossible to predict in advance how they might influence the clinical status of patients with pain.
Marcus and Grollman further advise that professional medical societies should urge Congress to revise DSHEA to give the FDA the necessary authority to regulate dietary supplements and mandate the withdrawal of dangerous products from the market. Along with that, the authors affirm, Congress should provide the FDA with the personnel and resources necessary for the task; however, it seems that with 75,000 products in the dietary supplements category to regulate the required resources could be unattainable in these times of budget austerity.
Meanwhile, as we have previously suggested in these UPDATES, it is vitally important that patients with pain exercise extreme caution when considering the supplements they purchase (caveat emptor), and to inform their healthcare providers of all products they are using. At the same time, healthcare providers need to be very skeptical of the possible benefits those products might afford patients and to strongly question whether they will help or hinder the pain care treatment plan (caveat medicus).
REFERENCE: Marcus DM, Grollman AP. The Consequences of Ineffective Regulation of Dietary Supplements. Arch Intern Med. 2012(Jul 9);172(13):1035-1036 [abstract here].
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