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.     

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.     

Medicamentos biocomparables en México: la postura del Colegio Mexicano de Reumatología, 2012

Biotechnological drugs (BTDs) are complex molecules whose manufacturing process precludes the ability to identically reproduce the structure of the original product, and therefore there cannot be an absolute equivalence between the original (innovative) medication and its biosimilar counterpart. BTDs have been proven useful in the treatment of several rheumatic diseases, however their high cost has prevented their use in many patients. Several BTD patents have expired or are close to expire, triggering the development of structurally similar drugs with efficacy and safety profiles comparable to the innovative compound; however, these must be evaluated through evidence based medicine. The Mexican General Health Law contemplates the registry of these biosimilar drugs for their use in our country. This document is a forethought from members of the Mexican College of Rheumatology, pharmacologists, and epidemiologists, in accordance with Mexican health authorities regarding the necessary scientific evidence required to evaluate the efficacy and safety of biosimilar drugs before and after their arrival to the Mexican market.     

Potential physician malpractice liability associated with complementary and integrative medical therapies

Physicians are increasingly grappling with medical liability issues as complementary and integrative health care practices are made available in conventional medical settings. This article proposes a framework in which physicians can assess potential malpractice liability issues in counseling patients about complementary and integrative therapies. The framework classifies complementary and integrative therapies according to whether the evidence reported in the medical and scientific literature supports both safety and efficacy; supports safety, but evidence regarding efficacy is inconclusive; supports efficacy, but evidence regarding safety is inconclusive; or indicates either serious risk or inefficacy. Clinical examples in each category help guide the clinician on how to counsel patients regarding use of complementary and alternative medical therapies in a given clinical situation. Specific strategies to reduce the risk for potential malpractice liability include the following: 1) determine the clinical risk level; 2) document the literature supporting the therapeutic choice; 3) provide adequate informed consent; 4) continue to monitor the patient conventionally; and 5) for referrals, inquire about the competence of the complementary and alternative medicine provider. This framework provides a basis for clinical decisions involving complementary and integrative care.     

Does the Evidence Make a Difference in Consumer Behavior? Sales of Supplements Before and After Publication of Negative Research Results

Objective  To determine if the public consumption of herbs, vitamins, and supplements changes in light of emerging negative evidence. Methods  We describe trends in annual US sales of five major supplements in temporal relationship with publication of research from three top US general medical journals published from 2001 through early 2006 and the number of news citations associated with each publication using the Lexus-Nexis database. Results  In four of five supplements (St. John’s wort, echinacea, saw palmetto, and glucosamine), there was little or no change in sales trends after publication of research results. In one instance, however, dramatic changes in sales occurred following publication of data suggesting harm from high doses of vitamin E. Conclusion  Results reporting harm may have a greater impact on supplement consumption than those demonstrating lack of efficacy. In order for clinical trial evidence to influence public behavior, there needs to be a better understanding of the factors that influence the translation of evidence in the public. The views presented are those of the authors and do not necessarily represent the positions or policies of the National Institutes of Health, the Department of Health and Human Services, or the US Public Health Service.     

Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects

OBJECTIVE: To review the literature on herbal preparations commonly utilized in the treatment of rheumatic indications. METHODS: Search of MEDLINE (PubMed) was performed using both the scientific and the common names of herbs. Relevant articles in English were collected from PubMed and reviewed. RESULTS: This review summarizes the efficacy and toxicities of herbal remedies used in complementary and alternative medical (CAM) therapies for rheumatologic conditions, by elucidating the immune pathways through which these preparations have antiinflammatory and/or immunomodulatory activity and providing a scientific basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced pro-IL-1beta gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but not for Sjogrens disease. The antiinflammatory actions of Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it may have a role in treating low back pain. While in vitro experiments with Tanacetum parthenium found inhibition of the expression of intercellular adhesion molecule-1, tumor necrosis factor alpha (TNF-alpha), interferon-gamma, IkappaB kinase, and a decrease in T-cell adhesion, to date human studies have not proven it useful in the treatment of RA. Current experience with Tripterygium wilfordii Hook F, Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while Urtica diocia and willow bark extract are effective for osteoarthritis. T. wilfordii Hook F extract inhibits the production of cytokines and other mediators from mononuclear phagocytes by blocking the up-regulation of a number of proinflammatory genes, including TNF-alpha, cyclooxygenase 2 (COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both decrease the production of TNF-alpha. At present there are no human studies on Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF-alpha, prostaglandin, and leukotriene synthesis and at present has limited efficacy in the treatment of osteoarthritis. CONCLUSIONS: Investigation of the mechanism and potential uses of CAM therapies is still in its infancy and many studies done to date are scientifically flawed. Further systematic and scientific inquiry into this topic is necessary to validate or refute the clinical claims made for CAM therapies. An understanding of the mechanism of action of CAM therapies allows physicians to counsel effectively on their proper and improper use, prevent adverse drug-drug interactions, and anticipate or appreciate toxicities. RELEVANCE: The use of CAM therapies is widespread among patients, including those with rheumatic diseases. Herbal medications are often utilized with little to no physician guidance or knowledge. An appreciation of this information will help physicians to counsel patients concerning the utility and toxicities of CAM therapies. An understanding and elucidation of the mechanisms by which CAM therapies may be efficacious can be instrumental in discovering new molecular targets in the treatment of diseases.     

Detection,evaluation, and treatment of severe and resistant hypertension: Proceedings from an American Society of Hypertension Interactive Forum held in Bethesda,MD, USA,October 10th 2013

The epidemiology, evaluation, and management of severe and resistant hypertension in the United States (US) are evolving. The American Society of Hypertension held a multi-disciplinary forum in October 2013 to review the available evidence related to the management of resistant hypertension with both drug and device therapies. There is strong evidence that resistant hypertension is an important clinical problem in the US and many other regions of the world. Complex drug therapy is effective in most of the patients with severe and resistant hypertension, but there are certain individuals who may be refractory to multiple-drug regimens or have adverse effects that make adherence to the regimen difficult. When secondary forms of hypertension and pseudo-resistance, such as medication nonadherence, or white-coat hypertension based on marked differences between clinic and 24-hour ambulatory blood pressure monitoring, have been excluded, the impact of device therapy is under evaluation through clinical trials in the US and from clinical practice registries in Europe and Australia. Clinical trial data have been obtained primarily in patients whose resistant hypertension is defined as systolic clinic blood pressures of ≥160 mm Hg (or ≥ 150 mm Hg in type 2 diabetes) despite pharmacologic treatment with at least three antihypertensive drugs (one of which is a thiazide or loop diuretic). Baroreceptor stimulation therapy has shown modest benefit in a moderately sized sham-controlled study in drug-resistant hypertension. Patients selected for renal denervation have typically been restricted to those with preserved kidney function (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m²). The first sham-controlled safety and efficacy trial for renal denervation (SYMPLICITY HTN-3) did not show benefit in this population when used in addition to an average of five antihypertensive medications. Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for clinical practice. At present, the focus on the management of severe and resistant hypertension will be through careful evaluation for pseudo-resistance and secondary forms of hypertension, appropriate use of combination pharmacologic therapy, and greater utility of specialists in hypertension.     

New and emerging antiarrhythmic drugs for atrial fibrillation: What may become available to the clinician in the near future

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major cause of morbidity. In the past decade, there have been significant advances in the nonpharmacologic management of AF. However, despite these advances there continues to be a great need for antiarrhythmic drugs to suppress AF. Existing medications have moderate efficacy for AF termination and suppression and have significant associated side effects, limiting their use. The need for new therapies has spawned the growth of several exciting drugs at various stages of development for the medical management of AF. Some agents are derivatives of currently available compounds, whereas others have been newly developed to focus on novel ion current targets. Dronedarone is the first antiarrhythmic agent in a decade to be recommended for approval by the US Food and Drug Administration for the management of AF. It is expected to a have a dramatically improved side effect profile, which likely will be the key factor in its prominence in our armamentarium in the future; however, dronedarone appears to have only moderate efficacy. Other novel agents are in various stages of development. Vernakalant, an “atrial selective” compound, will be useful in the acute chemical cardioversion of AF but not atrial flutter. Although vernakalant is similar in efficacy to ibutilide, it carries a significantly reduced risk of torsades de pointes. Ranolazine, initially developed for treating chronic angina, has important effects on ion currents potentially useful in arrhythmia management. Clinical trials specifically studying AF suppression will need to be performed before the utility of ranolazine can be extended. It is hoped that as our understanding of the pathophysiology of AF improves, innovative targets for pharmacologic therapy will emerge. However, the challenge of proving efficacy and safety in large randomized controlled trials will remain for any promising new agent.     

Complementary and Alternative Medicine Treatment Options for Otitis Media: A Systematic Review

Otitis media (OM) has numerous presentations in children. Together with conventional medical therapies aimed to prevent and/or treat OM, a rising number of complementary and alternative medicine (CAM) treatment options can be offered. Since OM is common in children, parents may ask healthcare professionals about possible CAM therapies. Many physicians feel that their knowledge is limited regarding these therapies, and that they desire some information. Therefore, we conducted a literature review of CAM therapies for OM, taking into account that many of these treatments, their validity and efficacy and have not been scientifically demonstrated.We performed a search in MEDLINE (accessed via PubMed) using the following terms: “CAM” in conjunction with “OM” and “children. Retrieved publications regarding treatment of OM in children which included these terms included randomized controlled trials, prospective/retrospective studies, and case studies.The following CAM options for OM treatment in children were considered: acupuncture, homeopathy, herbal medicine/phytotherapy, osteopathy, chiropractic, xylitol, ear candling, vitamin D supplement, and systemic and topical probiotics. We reviewed each treatment and described the level of scientific evidence of the relevant publications.The therapeutic approaches commonly associated with CAM are usually conservative, and do not include drugs or surgery. Currently, CAM is not considered by physicians a potential treatment of OM, as there is limited supporting evidence. Further studies are warranted in order to evaluate the potential value of CAM therapies for OM.     

Advising patients who seek complementary and alternative medical therapies for cancer

Many patients with cancer use complementary and alternative medical (CAM) therapies. Physicians need authoritative information on CAM therapies to responsibly advise patients who seek these interventions. This article summarizes current evidence on the efficacy and safety of selected CAM therapies that are commonly used by patients with cancer. The following major categories of interventions are covered: dietary modification and supplementation, herbal products and other biological agents, acupuncture, massage, exercise, and psychological and mind-body therapies. Two categories of evidence on efficacy are considered: possible effects on disease progression and survival and possible palliative effects. In evaluating evidence on safety, two types of risk are considered: the risk for direct adverse effects and the risk for interactions with conventional treatments. For each therapy, the current balance of evidence on efficacy and safety points to whether the therapy may be reasonably recommended, accepted (for example, dietary fat reduction in well-nourished patients with breast or prostate cancer), or discouraged (for example, high-dose vitamin A supplementation). This strategy allows the development of an approach for providing responsible, evidence-based, patient-centered advice to persons with cancer who seek CAM therapies.     

Are all angiotensin-converting enzyme inhibitors interchangeable?

In the treatment of most medical conditions, there are many choices. A critical question for practicing clinicians is: "Are all drugs within a class interchangeable?" In the past decade, the market has seen a proliferation of drugs within popular drug classes. The original drugs within a class typically have better scientific documentation than the newer ones, which are often referred to as "me-too" drugs. Due to a lesser financial investment, the latter may be available at a lower cost. Good reasons exist for grouping drugs, however, there is no accepted definition of the term "class effect." Although members of a drug class share main actions, they may have clinically important differences in terms of efficacy and safety. There are many such examples in the literature. This article reviews the class effect concept as it applies to the angiotensin-converting enzyme (ACE) inhibitors. Only half of the 10 ACE inhibitors available in the U.S. have been shown to improve survival and reduce morbidity in patients with heart failure or myocardial infarction. It is unknown whether the other five have the same safety and efficacy profiles or what their optimal doses are. Thus, we do not know whether all ACE inhibitors are fully interchangeable. The practice of medicine ought to be based on solid scientific evidence, not on assumptions or extrapolations. For our patients, such practice is a legitimate expectation. Therefore, it seems prudent to recommend that patients requiring ACE inhibitor therapy be prescribed one that has been proven effective and safe.     

When to initiate beta-blockers in heart failure: Is it ever too early?

Overwhelming clinical trial evidence confirms the efficacy and safety of β-blockers in patients with heart failure (HF) caused by systolic dysfunction. β-Blockers are recommended in national HF guidelines as standard of care therapy. Yet there is also a large body of evidence demonstrating that the use of β-blockers for HF is seriously inadequate under conventional care. This HF treatment gap is due, in part, to the persistence of perceptions—despite recent evidence to the contrary—that β-blocker therapy should be delayed until HF patients have been titrated to target doses of angiotensin-converting enzyme inhibitors and have been stable for at least 2 to 4 weeks after hospital discharge, and that early β-blocker initiation results in a substantial risk of worsening HF. Conversely, recent clinical trial evidence substantiates that β-blockers significantly reduce the risk of mortality and morbidity, including hospitalization for worsening HF, and have produced early survival benefits in patients with HF. It has also become evident that in-hospital initiation of lifeprolonging cardiovascular therapies, including β-blockers, has a positive impact on clinical outcomes and on longterm patient compliance. Overwhelming clinical evidence suggests that β-blockers should be administered to all stable HF patients without contraindication and that this therapy should be initiated as soon as possible to ensure that patients derive early and long-term improvements in clinical outcomes.     

Abatacept: a T-cell co-stimulation modulator for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a debilitating autoimmune disease that has traditionally been treated with disease-modifying anti-rheumatic drugs (DMARDs). In the European Union (EU), patients who fail to respond to traditional DMARDs may receive tumor necrosis factor-α (TNF-α) antagonists. However, approximately one-third of patients fail TNF-α antagonists due to adverse effects or lack of efficacy, and there are limited treatment options available to these patients. As knowledge of the underlying immunopathology of RA evolves, new strategies for inhibiting the inflammatory process have emerged. It is well known that activated T cells play a key role in orchestrating the immunopathological mechanisms of RA. Inhibiting the full activation of T cells is a rational strategy in the treatment of RA and represents a novel method of inhibiting disease activity, distinct from inflammatory cytokine blockade. Here, the safety and efficacy of abatacept, a selective T-cell co-stimulation modulator recently approved in the EU, is reviewed in patients with RA who have shown an inadequate response to TNF-α antagonists. In a randomized, placebo-controlled, double-blind, phase III trial of patients with an inadequate response to TNF-α antagonism, abatacept was effective in improving the signs and symptoms of RA, as well as patient-centered outcomes, such as fatigue, disability, and other mental and physical aspects of health-related quality of life. These improvements were sustained through 2 years during the open-label, long-term extension period. In this trial, abatacept demonstrated a safety and tolerability profile similar to placebo. Taken together, these data suggest that selective co-stimulation modulation with abatacept may be a viable option for patients who are refractory to both traditional therapies and TNF-α antagonists. An erratum to this article can be found at     

Status of hyaluronan supplementation therapy in osteoarthritis

Hyaluronans are polysaccharide molecules that occur naturally in synovial fluid; they help to create a viscous environment, cushion joints, and maintain normal function. The American College of Rheumatology recommends intraarticular injection of hyaluronans, which are available as several distinct therapeutic products, as an alternative to oral analgesics or nonsteroidal anti-inflammatory drugs for the symptomatic treatment of pain associated with osteoarthritis of the knee. A large body of literature supports the clinical efficacy and safety of this therapeutic class for this indication, although there are differences between the marketed products and they should be evaluated independently. Preliminary work investigating the use of hyaluronans for osteoarthritis in joints other than the knee has also produced promising results. There is growing evidence that hyaluronans, the biology of which is complex, may also have structure-modifying activity. Thus, compared with currently approved nonoperative therapies for osteoarthritis, hyaluronans may also have beneficial effects on the disease process in osteoarthritis.     

Complementary and alternative medicine in inflammatory bowel diseases: what is the future in the field of herbal medicine?

The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.     

Recent advances in alternative therapies

Complementary and alternative medicine (CAM) is becoming more popular, and CAM remedies are used instead of, or integrated with, orthodox allopathic therapies by many patients with asthma. Although most CAM remedies may have no discernible effects when analyzed by conventional medical techniques, some double-blind controlled studies do suggest that a meaningful benefit can be obtained with acupunture and homeopathic management in asthma. Herbal medicine is more popular, despite little evidence that the vast majority of herbs for asthma have any useful effects other than a nonspecific expectorant action. Dietary adjustment may benefit a small percentage of patients with asthma, but extreme measures are very rarely indicated. Formal pyschologic approaches can help some patients by reducing anxiety. Although most CAM approaches are harmless, the lack of benefit of many remedies and the potential harm from some of them must be recognized.