Extreme Complementary Alternative Medicine: A Case of Over-the-Counter Polypharmacy
ABSTRACT: Supplement use is the most common form of complementary and alternative medicine (CAM) in the United States. Patients taking supplements may not tell their physicians they are taking these agents, thinking they are innocuous because they are derived from nature. However, many factors need to be considered before taking supplements, including the patient’s overall health status (eg, comorbidities) and the potential for interactions with prescription medications, other supplements, and even food. The authors review these factors in the context of an extreme case of CAM in a patient with advanced Alzheimer’s disease. They also provide insights on discussing supplements with patients to ensure they are used safely and only when appropriate.
Complementary and alternative medicine (CAM) describes medical products and practices that are not part of standard Western medical care. The term complementary medicine is used when these medical products and practices are used in addition to standard medical care, whereas the term alternative medicine is used when they are used in lieu of standard medical care. Although the healthcare community generally frowns upon alternative medicine, more practices are starting to complement their standard treatments with CAM.
According to the National Institutes of Health (NIH), approximately 38% of US adults are using some form of CAM,1 which may include a variety of natural products (eg, vitamins, minerals, herbal supplements) and mind–body practices (eg, acupuncture, massage, meditation, chiropractic care, yoga). The most common reason patients turn to CAM is dissatisfaction with conventional medicine’s ability to adequately treat their chronic illnesses.2,3 Use of CAM has been found to be especially high among certain patient populations, including those who have Alzheimer’s disease, cancer, autoimmune diseases, HIV, or chronic pain.4-7 CAM use has also been found to be higher among women, former smokers, people with higher education, and people with a recent hospitalization.8
Use of dietary supplements is the most common form of CAM reported by US adults.1,8 According to the National Center for Health Statistics, more than 50% of the US population used at least 1 supplement between 2003 and 2006.9 This represents an increase of more than 10% compared with the 1988 to 1994 period. The data also show that women are more likely to use supplements than men.9
There is a general tendency to believe that herbal medicines and dietary supplements are safer than regular medicines. Many people see no problem with taking herbal medicines alongside conventional medicines10; however, patients are at high at risk for a potential drug–herb/dietary supplement interactions, with older adults being at especially high risk due to age-related physiologic changes and a high rate of polypharmacy.11 We report the case of a woman with advanced Alzheimer’s disease who was taking 59 different supplements daily. Her husband administered the supplements and reported being pleased with their effects.
A 76-year-old woman was brought to our rehabilitation facility because of generalized weakness, lethargy, and gait problems after experiencing a urinary tract infection. She was treated with antibiotics at a local hospital 4 days earlier. Upon arriving at our facility, she was afebrile and stable.
The patient’s medical history includes cervical spondylosis, insomnia, osteoarthritis, hyperlipidemia, hypothyroid, irritable bowel syndrome, osteoporosis, urinary incontinence, and severe Alzheimer’s disease, with a Mini-Mental State Examination score of 4/30. Her only prescribed medication is levothyroxine 100 µg daily to treat her thyroid disease. Her husband is her healthcare proxy. When the healthcare team at our institution first approached him regarding the patient’s care, he conveyed that he would not allow his wife to receive any medication other than levothyroxine. He even refused enoxaparin to prevent deep venous thrombosis, stating that this medication will increase his wife’s risk of bleeding due to the multiple supplements he gives her. He provided the healthcare team with a list of 59 different vitamins, minerals, and nutritional products that he administered to his wife daily (Table 1).
When reviewing the list, it became apparent that the patient receives a total of 130 pills every day, which are administered 3 times daily (Figure). When asked why he gives his wife so many nutraceuticals, he explained that his wife started having cognitive problems 12 years ago. He traveled with his wife to the best hospitals around the United States to find good treatment for her dementia. Subsequently, she received several commonly prescribed medications for this condition, including memantine, donepezil, and a rivastigmine transdermal patch, among other agents, but her condition never improved. In fact, he recounted that some medications made her dementia worse and caused several unwelcomed side effects, making him decide to take matters into his own hands. With the help of alternative medicine providers, he designed treatments with several nutraceuticals and multivitamins to slow the progression of his wife’s dementia and manage her other health conditions. He stated being pleased with the results of the treatments. Even though he acknowledged that his wife’s dementia progressed, he also explained that several of their relatives who had received a dementia diagnosis around the same time as his wife had already passed away.
When asked about the potential of his wife’s supplements to interact with each other and cause adverse effects, he stated that they are not more harmful than food because they are “natural.” He bought the supplements in bulk, with his wife’s monthly regimen costing approximately $1500. It is unclear what effect the supplements had on the patient; however, her last comprehensive metabolic panel and complete blood count were completely normal.
According to our search, out of the 59 vitamins, minerals, and nutritional products given to our patient, 45 did not have an indication or clear scientific evidence (A- or B-level evidence) per the Natural Standard database12 to support their intended purpose (eg, glutamine was given to boost the patient’s immune system, but there was only C-level evidence to support this indication). Therefore, we recommended discontinuing these agents (Table 1), which her husband partially complied with. Based on the patient’s medical history, current medical conditions, and scientific evidence, we did not have enough evidence to stop the remaining 14 supplements, and these were continued.
After the patient’s short hospitalization in the rehabilitation unit, she was discharged to home without any complications. At 3-month follow-up, the patient’s husband stated that he had discontinued many of the supplements per our discussion, but still kept the patient on approximately 20 of the supplements. The patient did not experience any improvement or deterioration while on the new regimen.
Figure. Pills given to the patient at dinnertime (left). As this photograph shows, most of the pills are large, potentially posing a choking hazard. When examining the patient’s weekly dinnertime regimen (right), the extent of the patient’s supplementation is put into context.
In 2009, US consumers spent more than $26 billion on supplements.13 A common motivation to take supplements includes the desire to stay healthy and to avoid prescription medications13; however, 34.3% of the US population take supplements along with their prescription medications.14 The rates are slightly higher among older adults (aged 57-85 years), with more than 50% this population taking supplements and prescription medications concomitantly.13 As the number of prescriptions increases, the likelihood of adverse effects also increases, as the patient is being exposed to an increasing number of active compounds. It has been reported that the risk of adverse effects is 15% with 2 medications, 58% with 5 medications, and 82% with 7 or more medications, without factoring in supplements15; however, supplements are well known to interfere with prescription medications. In 2012, Tsai et al published the results of their structured literature review, which found that St. John’s Wort, magnesium, calcium, iron, and ginkgo biloba had the greatest propensity to interact with medications, and that flaxseed, echinacea, and yohimbe had the largest number of documented contraindications.16 The authors also found that taking these and other supplements with medications affecting the central nervous system or cardiovascular system (eg, warfarin, insulin, aspirin, digoxin, ticlopidine) posed the greatest risks. Of the 882 drug interactions identified, 42.3% were attributed to the supplement altering the pharmacokinetics of the prescribed medication and 27.2% were considered major interactions.16
A recently published cross-sectional, observational study of a nationally representative sample of noninstitutionalized, civilian US adults aged 20 years and older (N=9950) from the 2005-2008 National Health and Nutrition Examination Survey (NHANES) found that dietary supplement use was 2.5 times more likely among patients with a physician-informed medical condition than among those who did not have an officially diagnosed medical condition, even after adjusting for age, sex, education, and household income.14 The most commonly reported supplements used among all participants included multivitamins that contained other ingredients (eg, minerals, botanicals) and antacids. The most prevalent prescription medications used in combination with a dietary supplement were cardiovascular agents (among those with a physician-informed medical condition) and hormones (among those without a physician-
informed medical condition). Based on their findings, the authors conclude that an official diagnosis may increase the risk of a patient adding dietary supplements to their prescription regimens.14
Our patient’s husband placed her on a supplement regimen after she received an Alzheimer’s diagnosis and a trial of a variety of antidementia agents failed to meet his expectations. Based on this experience, he only enabled her to take 1 prescription medication—levothyroxine. This restriction, while not ideal, likely prevented her from experiencing adverse effects from the high volume of supplements she was taking; however, she was receiving daily calcium, which is known to decrease the absorption of levothyroxine.17 Other agents that are known to interfere with levothyroxine absorption include iron and antacids; thus, such agents should not be administered within 4 hours of taking levothyroxine, per the prescribing information.17 The patient was also taking many other supplements, and it is unclear how these may have interacted with her levothyroxine, with each other, or with the foods she was eating. For example, she was receiving Ashwagandha, which is known to interact with thyroid agents, sedatives, antioxidants, and iron-containing foods, and she was taking Boswellia serrata, which is known to interact with high-fat foods.12 Tracking all of the potential interactions she could be at risk for is an impossible feat given the high volume of supplements she was taking and a lack of information on their synergistic effects.
Although our patient did not appear to experience any adverse effects from her supplement regimen, she also had advanced Alzheimer’s disease, placing her at high risk of swallowing problems. It has been estimated that 45% of institutionalized patients with dementia have dysphagia.18 The high prevalence of dysphagia in these patients has been attributed to age-related changes in neuropathology and sensory and motor function.18 Many of our patient’s pills were very large (Figure), which could have posed a choking hazard. In addition, having to swallow an assortment of pills 3 times daily may have been burdensome to the patient and negatively affected her quality of life.
Discussing Supplements With Patients
As our case and the literature show, physicians need to be more proactive in discussing supplements with their patients, particularly those who may have an increased propensity to add supplements to their regimen or replace their prescribed medications with nutraceuticals (eg, those with life-threatening or debilitating illnesses). We have compiled several Web-based resources that healthcare providers and patients alike can access to become more informed about dietary supplements and other CAM therapies(Table 2).
As previously mentioned, many people think vitamins, minerals, herbs, and other nutraceuticals are safe because they are derived from nature. They may not realize, however, that these agents have the ability to worsen medical conditions and to interact with medications, other supplements, and even with certain foods, reducing the efficacy of prescribed medications and of the supplements themselves. Patients may also not recognize that some minerals are needed in only trace amounts (eg, chromium); that fat-soluble vitamins are stored in the body and can lead to potential toxicity if taken in high doses (eg, vitamin E); or that certain herbs may cause renal damage or lead to toxicity if the individual is unable to clear these agents efficiently. Patients with impaired kidney or liver function may be at especially high risk because many prescribed medications and supplements are primarily cleared renally or hepatically, but as a case by Vanherweghem et al shows, the herbal preparation alone can have a considerable impact on the renal and hepatic system.19 The authors reported numerous cases of rapidly progressive interstitial renal fibrosis in young women (<50 years) receiving a weight loss remedy containing aristolochic acid, which was primarily derived from Aristolochia fangchi, a Chinese herb. Many of the patients on this regimen subsequently required renal transplants or dialysis, and several progressed to develop urothelial carcinoma. Although chemical analysis of some brands of this herb did not show any nephrotoxic contaminants of fungal or plant origin, or any contamination by diuretics or antiinflammatory drugs, the medicinal preparation of the capsules taken by these patients had different alkaloid profiles from those observed with the plants.19
Although the cases reported by Vanherweghem et al occurred in Belgium,19 the discrepancy they reported between properties observed in the herb versus the actual weight loss preparation leads to another important point that many patients may not realize, which is that the same stringent standards applied to prescribed medications in the United States are not applied to supplements. Although the FDA published Current Good Manufacturing Practices in 2007 to help ensure manufacturers produce safe, high-quality supplements, it is still the responsibility of the manufacturer to certify that the supplements are safe, free of contaminants, and that the information on the label is reflective of what is really in the bottle. The FDA does not actually test supplements to ensure their quality, but companies that have independently tested them have found standards to be lacking. Therefore, supplements should only be used under the supervision of a healthcare professional.
In general, most patients should be encouraged to eat a healthy diet, rather than taking supplements, to meet their nutritional needs. In most cases, whole foods are the best way for patients to receive the micronutrients they need, as studies that have examined whether dietary supplement can reproduce the same beneficial effects observed from nutrients contained in foods have often fallen short. For example, in December 2013, an editorial in the Annals of Internal Medicine suggested that multivitamins, the most commonly used supplements, provide no health benefits in the long-term and may actually be detrimental to overall health.20 This finding was based on 3 different studies published in the same issue of the journal. These studies examined the effects of multivitamins in a variety of populations with regard to cancer incidence, cardiovascular health, and cognitive health; however, all of the patients in these studies had normal nutritional status, no vitamin deficiencies, and did not have unique health concerns (eg, pregnancy), which might warrant the use of supplements. Therefore, as with prescribed medications, healthcare providers need to determine which patients may be candidates for and benefit from multivitamins, supplements, and other CAM therapies, and advise their patients accordingly.
Given the increasing number of patients using supplements in addition to prescription medications, healthcare providers must improve patient–provider communication regarding these agents. Patients should be made aware of the potential risk of adverse interactions, but physicians should remain respectful of patients’ values during these discussions and provide them with reliable, evidence-based information, as we did in discussions with our patient’s husband. Taking patients’ values and goals into consideration is essential for providing patient-centered care and can improve compliance with healthcare provider recommendations.
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12. Natural Standard. Foods, Herbs & Supplements database. www.naturalstandard.com/databases/herbssupplements/all/A. Accessed April 14, 2014.
13. ConsumerReports.org. What’s behind our dietary supplements coverage? www.consumerreports.org/cro/2012/04/what-s-behind-our-
dietary-supplements-coverage/index.htm. Published January 2011. Accessed April 8, 2014.
14. Farina EK, Austin KG, Lieberman HR. Concomitant dietary supplement and prescription medication use is prevalent among US adults with doctor-informed medical conditions. J Acad Nutr Diet. Published online ahead of print on April 4, 2014. www.ncbi.nlm.nih.gov/pubmed/24703929. Accessed April 11, 2014.
Bland CM. Polypharmacy and the elderly. Presented at: 2013 American College of Physicians Georgia Chapter Scientific Meeting; October 4-6, 2013; Savannah, GA. www.acponline.org/about_acp/chapters/ga/13-bland.pdf. Accessed March 18, 2014.
16. Tsai HH, Lin HW, Simon Pickard A, Tsai HY, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 2012;66(11):1056-1078.
17. Synthroid (levothyroxine sodium tablets, USP) [prescribing information]. North Chicago, IL: AbbVie Inc; 2012. www.rxabbvie.com/pdf/synthroid.pdf. Accessed April 14, 2014.
18. Easterling CS, Robbins E. Dementia and dysphagia. Geriatr Nurs. 2008;29(4):275-285.
19. Vanherweghem JL, Depierreux M, Tielemans C, et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet. 1993;341(8842):387-391.
20. Guallar E, Stranges S, Mulrow C, et al. Enough is enough: stop wasting money on vitamin and mineral supplements. Ann Intern Med. 2013;159(12):850-851.
Jorge Camilo Mora, MD, is a geriatrician and assistant professor at the Herbert Wertheim College of Medicine, Florida International University, Miami, FL.
Jerry O. Ciocon, MD, is a geriatrician and clinical associate professor at the Herbert Wertheim College of Medicine, Florida International University, Miami, FL.
Diana Galindo, MD, is a geriatrician at the Center for Geriatric Medicine Florida, Cleveland Clinic Florida, Weston, FL.