Despite the passing of the 1994 Dietary Health Supplement and Education Act, the marketing of dietary and natural products has continued to strain the consumer’s credulity while simultaneously seemingly staying at an arm’s length of the Federal Trade Commission’s and the Food and Drug Agency’s legal reach (1,2,3). In fact, since the passing of the act the industry has seen an exponential growth as the estimated number of supplements products increased from 4000 in 1994 to at least 55 000 in 2012 (4). In Canada, the situation isn’t any better.
A history of the DHSEA’s implications to the consumer’s health, and less importantly their pocketbook, is out of the scope of this post. However, great reviews can be found here and here for a Canadian perspective. The simplest way to put it is that contrary to prescriptions and over-the-counter (OTC) medications, supplements have a lower standard of safety and efficacy because they operate in a legal gray area where a multibillion industry can literally sell first and test later – if at all (5). The impact of dietary supplements on the consumer’s health are highlighted in a study by Geller et al. by the New England Journal of Medicine (4), which is subject of a today’s post.
Objective and Methods
The investigator’s objective was to “use a nationally representative surveillance data from 63 emergency departments obtained from 2004 through 2013 to estimate visits to U.S. emergency departments due to adverse events related to dietary supplements, and to identify and describe the associated characteristics of the patients, products and types of adverse event”.
This study is an analysis using the Adverse Drug Event Surveillance database system (NEISS-CADES)(6) conducted by the CDC, FDA and the Consumer Product Safety Commission (among others). Trained investigators looked at cases where the treating physician attributed emergency visits to to the use of dietary supplement(s). Products included were:
- herbal or complementary products (including botanicals, amino acids and microbial additives)
- micronutrients (vitamins and minerals)
- topically administered herbals and homeopathics
- excluding food or drinks (energy drinks, herbal tea beverages).
The reason for the use of supplements and also the adverse events were categorised. Those events were characterized as adverse reactions, allergic reactions, excess doses, unsupervised ingestion by children, or other events (e.g., choking). Deaths and intentional self-harm were not included at all in this study. Cases involving death were excluded because death registration practices vary widely between hospitals, and details are often lacking. Visits involving intentional self-harm, drug abuse, therapeutic failures, nonadherence, or withdrawal were also excluded.
Visits: The authors retrieved a total of 3667 cases and estimated a rate of 23 005 (*) emergency departments visits per year attributable to dietary supplement adverse event and 2154 hospitalizations annually. More than half of the visits were from female and caucasian; more than a quarter (28.8%) of emergency department visits attributable to a supplement-related adverse event were from individuals aged between 20-34 years of age; hospitalizations for elderly patients were twice as frequent as younger people (16.0% vs. 8.4% p=0.003); about 1 in 5 incidents involved accidental ingestion of supplements by children (less than 4 years old).
Products: A large majority of those ER departments visits was attributed to a single product (88.3%) as opposed to multiple products. After excluding accidental ingestion by children, 65.9% of ER visits were attributed to a single herbal or complementary nutritional product and 31.8% of cases were involved with a single micronutrient product. Weight loss and energy supplements were involved in 25% and 10% of the ER visits respectively.
Sex: While weight loss products were nearly twice as likely used in the female patients as opposed to men (30.4% and 17.6%, respectively), the latter group showed that 17.1% of them took sexual performance or bodybuilding products which were attributed to the ER visit (too few women to calculate rate).
Age: About two thirds (67%) of children under four and elderly patients (65 years old and above) in this study had micronutrients as the suspected agent which commonly included iron, calcium and potassium; conversely, at least half of the 5-19 and 20-34 year olds had their visit attributed to either a weight-loss or energy product.
Symptoms: The leading outcome attributed to the visit was adverse reaction (33.3%) followed by allergic reaction (23.6%), accidental ingestion by children (21.2%) and excessive dose (10.1%). The adverse reactions attributed to the supplements ranged from cardiovascular (chest pain, tachycardia, palpitations), neurological (headache, seizure, syncope, dizzyness, sensory or motor impairment), psychiatric (anxiety) to gastrointestinal (nausea, vomiting, abdominal pain) and anaphylaxis events.
Chest pain, palpitations and tachycardia were most often caused by weight loss or energy supplements (71.8%) which were affecting a large proportion young adults 20 to 34 years old (58%). Also, cardiac symptoms were frequently caused by bodybuilding (48.9%) or sexual-enhancement products (37.3%). As for micronutrients products, swallowing problems (choking, pill-induced dysphagia or globus) most frequently caused emergency visits due to calcium supplements (54.1%), while abdominal complaints (nausea/vomiting/pain) were primarily attributed to iron or potassium products.
This study shows from 2004 through 2013 in the United States, dietary supplements were implicated in 23 000 annual emergency department visits, of which about 1 in ten cases (2154) were serious enough to require hospitalization. Additional findings suggests that young and otherwise healthy adults (20-34 years old) were frequently presenting with cardiac symptoms (tachycardia, palpitations, chest pain) due to supplements used for weight loss, energy or bodybuilding purposes; children under 4 years of age were brought to ER departments with accidental ingestion of supplements (even with the supposedly child-proof iron products); older adults also commonly presenting with swallowing problems due to micronutrients (calcium, potassium,iron, etc).
Although, the study design (retrospective, cross-sectional surveillance database review) makes it somewhat difficult to determine causality between the specific supplement(s) and adverse events(s) beyond other confounding factors, their findings are still valid as they’re reasonably supported by the treating physician’s clinical suspicion. In other words, the supplements may not always have been the lone cause of the emergency visit, but are most probably the main cause or at the very least a major risk factor. However, this study does not speak to non-emergency settings, like outpatient clinics by specialists or primary care practices, nor to supplement-related deaths.
Even though the database used a validated and representative sample of US hospitals and minimum rate estimates were predicted beforehand, some rare adverse events may have not occurred frequently enough to have a statistically accurate annual estimation and this study did not try calculate for such events. On the other hand, this type of study is still more accurate than the current voluntary reporting of adverse events by supplement manufacturers (4). Clinicians should then use caution by relying on other evidence (7,8,9,10), or services (11), and their judgement to ascertain whether any supplement causes adverse events or supplement interactions.
Other limitations of the study include the fact that patients often don’t disclose their supplement use to physicians for various reasons, the dearth of supplement safety data and the subsequent lack of knowledge by clinicians of the true risks of supplements – all of which could lead this study to underestimate the true risks of dietary supplements. With the many regulatory and manufacturing problems of these products, clinicians must always consider the possibility that supplements may be contaminated with toxic substances, adulterated with prescription medications or may not even contain any of the listed ingredients.
Take home points of this study
- Dietary supplements are associated with 23 000 annual emergency department visits, of which about 1 in ten cases were serious enough to require hospitalization
- Weight-loss, bodybuilding and energy supplements are associated with cardiac symptoms (like tachycardia, chest pain, palpitations)
- Non-childproof and childproof dietary supplements are a common source of accidental ingestion in young children
- Elderly patients are also at risk of swallowing problems by dietary supplements due to the unregulated maximum tablet/capsule size
Implications of this study for patient safety***
- This study adds to the evidence which contradicts the myth that “natural means safe”
- It seems to be the first large-scale study that estimates an annual rate of ER visits and hospitalization due to dietary supplements
- Requiring dietary supplement companies to list potential adverse events to their product packaging and/or labels would help to better inform consumers and potentially prevent health problems (ie: “Cardiac or heart symptoms such as chest pain, palpitations and increased heart rate related to weight-loss, energy and bodybuilding products”)
- This study highlights a few specific manufacturing problems which could potentially be fixed by adding regulations on tablet/capsule size (lower than 250 mm) and regarding of childproof bottles
*Rates and percentages are measured as 95% Confidence intervals, unless noted otherwise
**access to full article and graphs were granted by Dr.Geller (lead author).
*** Implications are my own interpretations (pharmacist Nick) and not necessarily ones shared by any of the study’s investigators
U.S. Food and Drug Administration. FDA Press Release: FDA alerts companies to stop illegal sale of treatments for diabetes. July 23, 2013. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm362012.htm
Office of Inspector General, Department of Health and Human Services. Dietary Supplements: Structure/Function Claim Fail To Meet Federal Requirements. October 2012. Available at: https://oig.hhs.gov/oei/reports/oei-01-11-00210.pdf
Federal Trade Commission. Miracle Health Claims & Dietary Supplements. October 2011. Available at:https://www.consumer.ftc.gov/articles/pdf-0112-miracle-health-claims-and-dietary-supplements.pdf
Geller AI, Shehab N, et al., Emergency Department Visits for Adverse Events Related to Dietary Supplements. N Engl J Med. 2015 Oct 15;373(16):1531-40. doi: 10.1056/NEJMsa1504267.
US Department of Health and Human Services, Food and Drug Administration. New Dietary Ingredients in Dietary Supplements – Background for Industry: http://www.fda.gov/Food/DietarySupplements/NewDietaryIngredientsNotificationProcess/ucm109764.htm (accessed 03/12/15)
Mendelson AB, Presentation: The National Electronic InjurySurveillance System: CooperativeAdverse Drug Events SurveillanceSystem (NEISS-CADES), Office of Drug Safety, Federal Drug Agency, 05/2008 : http://www.fda.gov/ohrms/dockets/ac/05/slides/2005-4143S1_09_Mendelsohn_files/frame.htm
Posadzki P, Watson LK, Ernst E, Adverse effects of herbal medicines: an overview of systematic reviews.,Clin Med. 2013 Feb;13(1):7-12.
An exhaustive, but time-consuming way of ascertaining the true risks of dietary, natural or alternative products is do consult the literature in a medical search engine such as Pubmed
Specialized textbook or online databases such as Comprehensive Natural Medicine Database, Natural Standards, or even Lexi-Comp and Up-to-Date softwares
Drug/Poison information centers