Cardiovascular adverse effects of herbal medicines: a systematic review of the recent literature

Herbal medicines are popular but health care professionals often feel uncertain about their risks. This article summarizes recent evidence regarding the serious or potentially serious cardiovascular adverse effects of herbal medicines. Five electronic literature databases were searched. The evidence found was mostly anecdotal. Case reports and case series indicate that life-threatening adverse effects of herbal medicines occur. Potentially serious adverse effects are arrhythmias, arteritis, cardiac glycosides overdose, chest pain, congestive heart failure, hypertension, hypotension, myocardial infarction, over-anticoagulation, pericarditis and death. The problems relate to toxic herbal ingredients, adulteration and contamination of herbal medicinal products, and herb-drug interactions. Herbal medicines that have been implicated repeatedly include aconite, ephedra and licorice. Because of the anecdotal nature of the evidence, it is impossible to estimate the incidence of adverse effects. In conclusion, herbal medicinal products are regularly associated with serious cardiovascular adverse events but the size of this problem cannot be estimated at present. Vigilance and research seem to be the best way forward.     

Acute liver injury following <Emphasis Type="Italic">Garcinia cambogia</Emphasis> weight-loss supplementation: case series and literature review

Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb–drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.     

Adverse effects of herbal treatment of cardiovascular disease: what the physician must know

The increasing use of herbal products by patients with cardiovascular disease represents a clinical challenge to physicians. The use of herbal products is increasing in our society, and less than 50% of patients using herbal products report this information to their physicians. In addition, physicians often lack the knowledge base for herbal medications to effectively counsel patients regarding adverse effects and potential herb-drug interactions. This article reviews Western and traditional Chinese herbs that are commonly used by patients with cardiovascular diseases, herbs noted to have adverse cardiovascular effects, and herbs that may potentially interact with commonly prescribed cardiovascular medications.     

Herbs and alternative therapies: Relevance to hypertension and cardiovascular diseases

Herbal remedies, supplements, and alternative therapeutic items are used by many patients with hypertension and cardiovascular diseases. Scientific knowledge about their efficacy and safety is lacking, and unfortunately, physicians are frequently not aware that patients are using these nontraditional forms of medical care. Patients may anticipate physicians’ disapproval of their use, or not realize that it is important for the physician to know what they are taking. Therefore, it is imperative that patients are asked nonjudgmental questions about current and past use of herbals and alternative therapies. Even when physicians are aware of such use, they feel poorly trained to identify the constituents and effects. Although many such therapies are innocuous, several herbal or alternative therapeutic items can significantly elevate blood pressure or cause interactions with cardiovascular drugs. Practitioners in cardiovascular medicine should be competent and know current scientific evidence for the benefits and adverse effects of herbal supplements and provide patients reasonable advice. In this brief article, we review the epidemiology of alternative therapy use, and select several important herbal or other supplements that patients with hypertension and cardiovascular diseases may be taking. We discuss the therapies considered biological in nature as opposed to mind-body interventions or manipulative body or energy therapies.     

Herbal medicine: Beneficial effects,side effects,and promising new research in the treatment of arrhythmias

Herbal medications and dietary supplements are unregulated in the United States. The use of these medications has dramatically increased over the past decade. Many of these drugs are biologically active, yet physicians are often unaware their patients are using a traditional remedy. Physicians are frequently unfamiliar with the medications being used and the intended effect, as well as the side-effect profiles that accompany them. Recently, some of the herbal mediations that are commonly used in the general population have been shown to be beneficial for the treatment of arrhythmias. Unfortunately, many more have been shown to be detrimental. In this article, the background behind herbal medication and the degree to which herbal medications are being used is reviewed. Herbal medications known to have beneficial effects in the treatment of arrhythmias, as well as those that have known detrimental effects with regard to cardiac arrhythmias, are highlighted. Finally, research that has been done in this field, focusing on those compounds that have been shown to be biologically active in the treatment of cardiac arrhythmias, are reviewed.     

Herbs and dietary supplements in the prevention and treatment of cardiovascular disease

Herbs and dietary supplements can have significant physiological effects. Garlic (Allium sativum) has shown beneficial lipid effects in a majority of trials; dried garlic preparations are superior to oil preparations. There is preliminary evidence that indicates that hawthorn (Crataegus species) may provide benefit in congestive heart failure. Coenzyme Q also may be of benefit in congestive heart failure. Although observational studies indicate a protective effect of dietary or supplemental vitamin E, controlled trials have not shown a beneficial effect on angina and have been mixed on whether supplementation decreases major cardiac events. Although several observational studies have noted that fish intake protects against cardiovascular disease, prospective studies are less impressive. Fish oil supplementation may have a mild beneficial effect on hypertension, but there is no effect on total cholesterol levels. Trials are inconsistent on whether fish oil reduces restenosis rates following coronary angioplasty. Carnitine appears to have beneficial effects on congestive heart failure and angina; there is also preliminary evidence that arginine may benefit patients with congestive heart failure or angina. Herbs and supplements have been associated with adverse effects and interactions; for example, garlic inhibits platelet aggregation and can cause significant anticoagulation, and the Chinese herb danshen (Salvia miltiorrhiza) appears to potentiate warfarin. Several herbs and supplements hold promise as adjuncts in the prevention and treatment of cardiovascular disease. There is a need for definitive research on the potential risks and benefits of these compounds, including appropriate dosages and formulations, and delineation of adverse events and interactions     

Commonly used herbal medicines in the United States: a review

Herbal medicines are widely used in the United States, with approximately one quarter of adults reporting use of an herb to treat a medical illness within the past year. Herbs contain complicated mixtures of organic chemicals, the levels of which may vary substantially depending upon many factors related to the growth, production, and processing of the herbal product. While many manufacturers attempt to provide products with consistent levels of suspected active ingredients through a process known as standardization, this technique has uncertain effects on the safety and efficacy of the final product. Herbs are considered to be dietary supplements in the United States and therefore are subjected to a very limited form of regulation and oversight. Although herbs are often believed to be "natural" and therefore safe, many dangerous and lethal side effects have recently been reported, including direct toxic effects, allergic reactions, effects from contaminants, and interactions with drugs and other herbs. Of the ten most commonly used herbs in the United States, systematic reviews have concluded that only four are likely to be effective, and there is very limited evidence to evaluate the efficacy of the approximately 20,000 other available herbal products. Because herbs may contain potent bioactive substances and are often marketed to treat specific diseases, many have argued that they should be subject to more stringent regulation, similar to over-the-counter drugs. To improve the safety and consistency of herbs, additional research is needed to define the pharmacology, stability, and bioavailability of these products.     

When is a herb a drug?

With the growing popularity and use of herbal remedies in the industrial countries there has been an increasing recognition and reporting of adverse reactions. Drug development represents discovery and characterization of naturally occurring plant metabolites or their synthetic analogues. Therefore, a herbal remedy should be considered a drug for all clinical purposes. The liver, being central to the metabolism of virtually all xenobiotics, is inevitably exposed to reactive metabolites and liver injury is a potential complication of nearly every medication, including herbal remedies. Recognition of herb induced hepatotoxicity depends on clinical awareness of the problem, a suspicion that a herbal preparation is involved, and detailed enquiry regarding the use of all supplements and remedies. Herbal medicines should be regulated more systematically and monitoring for adverse reaction should improve.     

Adverse events of herbal food supplements for body weight reduction: systematic review.

Herbal weight-loss supplements are marketed with claims of effectiveness. Our earlier systematic review identified data from double-blind, randomized controlled trials for a number of herbal supplements. The aim of this systematic review was to assess all clinical evidence of adverse events of herbal food supplements for body weight reduction for which effectiveness data from rigorous clinical trials exist. We assessed Ephedra sinica, Garcinia cambogia, Paullinia cupana, guar gum, Plantago psyllium, Ilex paraguariensis and Pausinystalia yohimbe. Literature searches were conducted on Medline, Embase, Amed and The Cochrane Library. Data were also requested from the spontaneous reporting scheme of the World Health Organization. We hand-searched relevant medical journals and our own files. There were no restrictions regarding the language of publication. The results show that adverse events including hepatic injury and death have been reported with the use of some herbal food supplements. For herbal ephedra and ephedrine-containing food supplements an increased risk of psychiatric, autonomic or gastrointestinal adverse events and heart palpitations has been reported. In conclusion, adverse events are reported for a number of herbal food supplements, which are used for reducing body weight. Although the quality of the data does not justify definitive attribution of causality in most cases, the reported risks are sufficient to shift the risk-benefit balance against the use of most of the reviewed herbal weight-loss supplements. Exceptions are Garcinia cambogia and yerba mate, which merit further investigation.     

Cardiovascular considerations in using topical, oral, and intravenous drugs for the treatment of glaucoma and ocular hypertension: focus on beta-adrenergic blockade

Glaucoma and ocular hypertension are highly prevalent conditions in individuals over the age of 40 and are commonly seen together in patients with cardiovascular disease. Many of the antiglaucoma medications, when systemically absorbed, affect the sympathetic and parasympathetic nervous systems of patients and can cause cardiovascular toxicity. Such adverse effects are frequently associated with the long-term use of potentially toxic agents in elderly people, who are most prone to chronic eye disease. Moreover, patients may not associate their symptoms with the topical eye medications, and consequently may not report adverse drug effects. Drug-drug interactions can also occur when patients are taking medications for both cardiovascular disease and glaucoma. This review focuses on beta-adrenergic blockers as topical antiglaucoma medications and other topical antiglaucoma drugs. The systemic toxicity of these agents is reviewed, along with the possible drug interactions. Brief mention is also made of other antiglaucoma medications used alone and in combination with topical beta-blockers.     

Interactions between dietary supplements in hospitalized patients

Inpatient consumption of dietary and herbal supplements (DHS) has recently received research attention, particularly due to potential DHS–drug interactions. Nevertheless, DHS–DHS interactions have seldom been evaluated among hospitalized patients. We evaluated potential DHS–DHS interactions among inpatients. The study was a cross-sectional prospective study, conducted at Bnai Zion Medical Center (Haifa, Israel) in 2009–2014. A multi-disciplinary team of researchers constructed a questionnaire aimed at detecting DHS use among inpatients. The Natural Medicine Database was used to examine identified DHS for potential DHS–DHS interactions. Then, medical files were reviewed to identify side effects potentially caused by such interactions and rate of documentation of DHS use. Univariate and multivariate logistic regression analyses were conducted to characterize potential risk factors for DHS–DHS interactions among hospitalized DHS users. Of 927 patients who agreed to answer the questionnaire, 458 (49.4 %) reported the use of 89 different DHS. Potential DHS–DHS interactions were identified in 12.9 % of DHS users. Three interactions were associated with the actual occurrence of adverse events. Patients at risk of DHS–DHS interactions included females (p = 0.026) and patients with greater numbers of concomitant medications (p < 0.0001) and of consumed DHS (p < 0.0001). In 88.9 % of DHS users, DHS use was not reported in medical files and only 18 % of the DHS involved in interactions were documented. Potential DHS–DHS interactions are common in inpatients, and may lead to hospitalization or worsen existing medical conditions. The causal relationship between potential interactions and actual adverse events requires further study.     

A rare cause of drug-induced hepatitis in an immunocompromised patient and the role of glutathione

The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the mostcommon outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.     

Vitamins, supplements, herbal medicines, and arrhythmias

Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.     

Cardiovascular and respiratory considerations with pharmacotherapy of glaucoma and ocular hypertension

Glaucoma and ocular hypertension are highly prevalent conditions in individuals over the age of 40 and are commonly seen together in patients with cardiovascular disease. Many of the antiglaucoma medications, when systemically absorbed, affect the sympathetic and parasympathetic nervous systems of patients and can cause cardiovascular toxicity. Such adverse effects are frequently associated with the long-term use of potentially toxic agents in elderly people, who are most prone to chronic eye disease. Moreover, patients may not associate their symptoms with the topical eye medications, and consequently may not report adverse drug effects. Drug-drug interactions can also occur when patients are taking medications for both cardiovascular disease and glaucoma. In this review, the systemic toxicity of these agents is reviewed, along with possible drug-drug interactions. Mention is made of other antiglaucoma medications used alone and in combination with topical beta-blockers. Identification of genetic loci-a bold new step toward glaucoma treatment-is mentioned briefly at the end of the article.     

Herbal Medicine in the United States: Review of Efficacy,Safety, and Regulation

Introduction  Herbal products have gained increasing popularity in the last decade, and are now used by approximately 20% of the population. Herbal products are complex mixtures of organic chemicals that may come from any raw or processed part of a plant, including leaves, stems, flowers, roots, and seeds. Under the current law, herbs are defined as dietary supplements, and manufacturers can therefore produce, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Although herbs are often perceived as “natural” and therefore safe, many different side effects have been reported owing to active ingredients, contaminants, or interactions with drugs. Results  Unfortunately, there is limited scientific evidence to establish the safety and efficacy of most herbal products. Of the top 10 herbs, 5 (ginkgo, garlic, St. John’s wort, soy, and kava) have scientific evidence suggesting efficacy, but concerns over safety and a consideration of other medical therapies may temper the decision to use these products. Conclusions  Herbal products are not likely to become an important alternative to standard medical therapies unless there are changes to the regulation, standardization, and funding for research of these products.     

Alternative medicine in atrial fibrillation treatment—Yoga,acupuncture, biofeedback and more

The last decade has seen a significant improvement in the management of atrial fibrillation (AF) with the development of newer medications and improvement in catheter ablation techniques. Recurrence of AF remains a significant problem in these patients and medications offer limited supportive role. Complementary and alternative treatment strategies therefore remain a viable option for these AF patients. Several studies have shown improvement in AF symptoms with yoga therapy, acupuncture and biofeedback. There are also several herbal medicine and supplements such as omega-3 fatty acids, antioxidant vitamins, barberry, motherwort, cinchona, Shensongyangxin, hawthorn, Kella and Wenxin Keli that have been evaluated as potential therapeutic options in AF. These studies are however limited by small sample sizes with mixed results. Besides the pharmacological action, metabolism, interactions with other medications and the adverse effects of the herbal medications and supplements remain poorly understood. In spite of the above limitations, complementary therapies remain a promising option in the management of AF and further studies are necessary to validate their safety and efficacy.