HERBS

 

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A SCIENTIFIC LOOK AT ALTERNATIVE MEDICINE

Herbs

Thomas J. Wheeler, Ph.D.

Associate Professor (retired), Department of Biochemistry and Molecular Biology,

University of Louisville School of Medicine, Louisville KY

thomas.wheeler@louisville.edu

Revised 2020

This material was originally part of a handout for an elective course given to medical students at the University of Louisville.

Copyright 2020.  Permission to copy for non-profit uses is granted as long as proper citation of the source is given.

DISCLAIMER: The material presented here is not medical advice.  It represents the author's summary of scientific evidence concerning various topics.  For medical advice, see your physician.

Note on topic coverage: this article deals primarily with plant materials that are not normally considered food items (though some spices are discussed). For food items, see the article on dietary supplements. Traditional herbal medicines of China, Japan, and India are discussed in the article on Eastern approaches, though many of the general principles presented in this article are applicable.


CONTENTS

Herbs: General Aspects

    Overview

    Regulation

    Preparation

    Arguments in favor

    Reviews (multiple herbs)

    Potential toxicity

    Scientific critique

    Nonscientific aspects

Some Popular Herbs

References

HERBS: GENERAL ASPECTS

OVERVIEW

The FDA distinguishes between herbal products and botanicals. “According to the US Food and Drug Administration (FDA) definition, a botanical is a product that consists of vegetable materials that may include plant materials, algae, microscopic fungi, or combinations thereof. Herbal products are defined as supplements that contain one or more herbs (seed-producing plant that does not develop persistent woody tissue, dies down at the end of the growing season) (Merriam-Webster). In general, herbals or botanicals can be divided into three broad categories. The first category includes crude herbal products directly gathered from plants such as berries, seeds, flowers, bark of trees, etc. Such products most often belong to the realm of traditional herbal medicine and have been used for generations by lay people and/or under the direction of experienced herbalists...The second category consists of botanicals that are chemical compounds derived from plants. These botanicals are the basis of many well-known drugs such as digitalis (derived from foxglove), colchicine (derived from autumn crocus), and paclitaxel (derived from pacific yew)...The third category comprises a relatively recent addition to the world of herbals and botanicals and frequently constitutes multi-ingredient formulations that are commercially produced and marketed for the purposes of improving well-being and treating a range of illnesses” (Roytman et a. 2018. Clin Pharmacol Ther. 104(3):458-69). This article deals with items in the first class. Products in the third class are dealt with in the article on dietary supplements.

“Over 4 billion people, or 80% of the world’s population, use herbal remedies as their source of primary care” (Werner 2014. Front Pharmacol. 5:142). A 2015 survey found that about 35% of American adults used herbs. "The most frequent conditions associated with herbal supplement use were a stroke (48.7%), cancer (43.1%), and arthritis (43.0%)...Older age and higher education were associated with a higher use of herbal supplements. People with chronic diseases are more likely to use herbal medicines than others" (Rashrash et al. 2017. J Patient Exp. 4(3):108-13). A 2002 survey found that "Roughly two thirds of adults using commonly consumed herbs (except echinacea) did not do so in accordance with evidence-based indications" (Bardia et al. 2007. Mayo Clin Proc. 82(5):561-6).

The estimated sales of herbs in the US was $8 billion in 2017, double the level of 2003. Half of this was direct sales (internet and multilevel marketing). Herbs are sold by major pharmaceutical companies, and are marketed for a wide variety of medical conditions. Most of these are self-limiting or mild conditions, but some remedies are promoted for cancer and other serious illnesses. There are now many snacks and drinks containing herbal ingredients (e.g., ginkgo, St. John's wort). In 2001 the FDA began warning companies that such herbal additives may be illegal.

About 250 herbs are on the FDA's "Generally Recognized as Safe" list. However, some of these are for use as flavors and spices, and medical uses may not be safe.

"Herbs contain hundreds of active ingredients that may be potentially useful for the development of therapeutic agents. Identification and isolation of phytochemical groups and/or single chemical entities from herbs or plant materials are therefore crucial for drug discovery. It has been estimated that there are at least 15 major phytochemical groups in herbs...each group contains many individual chemical entities. For instance, flavones include more than 9,000 known structures. Alkaloids are an important class of active ingredient in herbs/plants, and more than 10,000 alkaloids have been isolated, of which more than 80 compounds have been clinically used...The same family or genus of plants often contains the same or similar chemical components. For example, belladonna, Solanaceae, and Datura genus contain the same substance, scopolamine. The same compound can also be distributed in different families so that berberine is not only found in berberidaceae, but also in ranunculaceae and rutaceae plants. Saponins from Panax ginseng can also be found in Panax notoginseng (Burk.) F.H. Chen, another THM [traditional herbal medicine] distributed throughout the southwest of China, Burma, and Nepal. The same bioactive ingredients may be present in various plant parts; for example, ginseng leaf stem contains numerous active ingredients (ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids, and fatty acids), and they also present in the root. The same plant species can often contain different kinds of compounds of the same class; for example, there are 25 and 70 kinds of alkaloids identified in raw opium and vinca, respectively" (Pan et al. 2013. Evid Based Complement Alternat Med. 2013:627375).

Multi-extract formulations "are known in the DS [dietary supplement] industry as 'proprietary blends,' a designation that may or may not represent true marketing exclusivity or ownership. A significant problem with proprietary blends is that many, if not most, of these combinations have never been administered to humans prior to marketing, and the pharmacological repercussions are unknown" (Gurley et al. 2018. Clin Pharmacol Ther. 104(3):470-83).

In 1999-2000 NIH began funding four university centers to study botanicals, with additional centers funded in later cycles. In 2002 the National Institute of Standards and Technology was asked by NIH to develop standard reference materials for use in quality control during manufacture of botanicals.

The German government (Commission E) conducted a systematic review of herbs from 1978 to 1994. Its monographs have been translated and are available in the U.S. However, the scientific status of these reports is questionable; they have relied heavily on uncontrolled studies, historical evidence, and anecdotal reports. With respect to safety, they are more trustworthy. Overall, 380 herbs were considered, with 254 approved as safe and reasonably effective.

Vickers and Zollman (1999. BMJ 319(7216):1050-3) pointed out three important differences between herbal medicine and conventional pharmacy:

Ernst (2007. Postgrad Med J. 83(984):615-6) described three types of herbal medicine:

The first form of herbal medicine is perhaps best called phytotherapy. It is the scientific face of herbalism and the area where reasonably good data are available. In phytotherapy, we accept that one extract of St John's wort (Hypericum perforatum), for example, contains a multitude of pharmacologically active ingredients. Thus isolating one of them is often not the way forward. Instead, the whole extract is viewed as a single entity which can be standardised and clinically tested for one defined clinical condition. If all tests turn out to be positive, and the extract (for example, St John's wort) does demonstrably generate more good than harm (for example, alleviates symptoms without unacceptable risks), it can be used for one clearly defined condition (for example, mild to moderate depression). Phytotherapy thus closely follows the principles of pharmacotherapy...

The second form of herbal medicine refers to the hugely popular over-the-counter (OTC) market of plant-based preparations currently sold as dietary supplements...The vast majority are not supported by scientific evidence. This is the first major contrast to phytotherapy. The second is the absence of patient–clinician interactions. Customers buy OTC herbal supplements without consulting any healthcare professional; their impetus and "knowledge" usually comes from what the popular media report....

The third form of herbal medicine is the one practised by traditional herbalists worldwide...Traditional herbalism has nothing to do with the fact that St John's wort, for example, has been shown to be effective for depression. Traditional herbalists do not even think in conventional disease categories and hold beliefs abandoned by the rest of medicine 200 years ago—a "damp" and "cold" condition requires a "dry" and "hot" remedy, for example. The medicine prescribed by traditional herbalists would typically not be an extract of a single herb but an individualised mixture of several plant extracts. The composition of this mixture depends on the characteristics of each individual patient...As traditional herbalists use mixtures of multiple extract, safety issues are much more critical than in phytotherapy. The potential for toxicity, herb drug interactions, contamination, or adulteration increases in parallel with the number of plants in the mixture. Today there is not a shred of scientific evidence to demonstrate that traditional herbalists do more good than harm.

Key points for physicians: herbs are drugs, with contraindications and potentially dangerous interactions with other drugs. Patients may not inform you that they are using herbs unless asked specifically. In general, herbs should be avoided in pregnancy and lactation (an estimated 40% of pregnant women use herbs!). Some herbs affect blood glucose and should be avoided in diabetes. The American Society of Anesthesiologists has recommended discontinuing herbs 2-3 weeks prior to surgery.


REGULATION

In the United States, herbs are regulated as dietary supplements (1994 Dietary Supplement Health and Education Act, DSHEA) (see the article on dietary supplements for a discussion of the regulations). Thus, unlike over-the-counter drugs, they do not need to have demonstrated safety and effectiveness. A survey of Internet retail sites for herbs found that 55% made claims to treat or prevent disease (which is illegal under DSHEA).

"In response to concerns regarding botanical integrity and quality assurance, the U.S. FDA recently instituted the requirement that botanical dietary supplements under its jurisdiction be prepared using good manufacturing practice (GMP). These guidelines complement the advertising and labeling regulations required by the U.S. Federal Trade Commission and are similar to those in effect in the EU. Enforcement of these regulations is helping to ensure that consumers are able to purchase accurately labeled botanical dietary supplements that are not contaminated with heavy metals, pesticides, herbicides, or microbes. However, these regulations do not require testing of botanical dietary supplements for potential adverse interactions with prescription medicines nor do they require evidence of efficacy" (van Breeman 2015. J Med Chem. 58(21):8360-72).

"To make therapeutic claims, the products have to register as medicinal drugs and undergo the FDA's rigorous, expensive and lengthy drug approval process - which, like the European regulations, requires complex biochemical analyses and three phases of clinical trials. It's not surprising that only one herbal medicine has achieved this status: sinecatechins, a tea polyphenol for the topical treatment of cervical warts"  (Gilbert 2011. Nature. 480(7378):S98-9).

"The Traditional Herbal Medicinal Products Directive (THMPD) came into force across the European Union (EU) in April 2011...Under the directive, herbal medicines intended as treatments for minor health ailments must be registered as traditional-use products with the regulatory agency in every EU member state in which the product is to be sold (although each national regulatory agency is supposed to recognize licences already granted by other EU members). This system is designed to make it less likely that a product is sold as a traditional herbal medicine in one country and as something else in another...The THMPD does not cover practitioners of herbal medicine, who are still permitted to mix herbal remedies from individual components for personal prescriptions. Products are eligible for licence as a traditional herbal medicine only if they have been used to treat a specified health complaint for at least 30 years, including a minimum of 15 years in Europe" (Ibid.).


PREPARATION

Decoction "is a method of extraction by boiling herbal or plant material to dissolve the chemicals of the material" (Wikipedia). "In traditional medicines, herbal remedies are mainly made of a decoction from a mixture of raw herbs, and this dosage form is still widely used in China, Japan, and Korea. The disadvantages of herbal decoction include (1) inconvenience in terms of usage, (2) unstable in composition, and (3) issues related to quality control. The deficiencies of herbal decoctions can be overcome by using herbal extracts. Plant/herbal extracts, including those derived from THMs [traditional herbal medicines], have become a popular dosage form of phytomedicine and/or health products in the global market. In the USA, while health products based on plant/herbal extracts constitute more than 95% of market share in herbals, raw herbs comprise less than 5%" (Pan et al. 2013. Op. cit.).


ARGUMENTS IN FAVOR OF HERBS

Herbs have been sources of useful drugs. Many remain to be scientifically examined; it is likely that some traditional herbal remedies may contain pharmacologically useful compounds.

The value of some herbs is supported by controlled studies (see reviews in the sections below).

They are often less expensive than prescription drugs.


REVIEWS (MULTIPLE HERBS)

All conditions - Guo et al. 2007. Postgrad Med J. 83(984):633-7: "There is a sparsity of evidence regarding the effectiveness of individualised herbal medicine and no convincing evidence to support the use of individualised herbal medicine in any indication."

Breastfeeding - Budzynska et al. 2014. Pediatr Rev. 34(8):343-52: "Galactagogues are herbs or medications that increase breast milk production...Galactagogues include common culinary herbs, such as fennel seed (Foeniculum vulgare), anise seed (Pimpinella anisum), caraway seed (Carum carvi), dill seed (Anethum graveolens), fenugreek (Trigonella foenum-graecum), and alfalfa herb (Medicago sativa). Other galactagogues include goat’s rue herb (Galega officinalis), torbangun (Coleus amboinicus), blessed thistle herb (Cnicus benedictus), and milk thistle seed (Silybum marianum). Despite the long history of use of herbal galactagogues, scientific research is limited, and little is known about the mechanism of action or relative efficacy."

Dysmenorrhea - Pellow and Nienhuis 2018. Complement Ther Med. 37:13-26 : “Most of the evaluated medicinal plants showed evidence of efficacy in relieving menstrual pain in at least one RCT. The low or unclear quality of the majority of these studies however warrants caution in interpreting these results.”

Fatty liver disease - Liu et al. 2013. Cochrane Database Syst Rev. CD009059: "Some herbal medicines seemed to have positive effects on aspartate aminotransferase, alanine aminotransferase, ultrasound, and computed tomography. We found no significant difference on adverse effects between herbal medicine and control groups. The findings are not conclusive due to the high risk of bias of the included trials and the limited number of trials testing individual herbal medicines."

Headache - Levin 2012. Headache. 52 Suppl 2:76-80: "Butterbur and feverfew are the 2 herbal oral preparations best studied, and they seem to have real potential to help many patients with migraine and perhaps other headache types."

Induction of labor - Zamawe et al. 2018. BMJ Open. 8(10):e022499: "The findings suggest that herbal medicines for IOL are effective, but there is inconclusive evidence of safety due to lack of good quality data. Thus, the use of herbal medicines for IOL should be avoided until safety issues are clarified." However, Ernst (2018 Nov 5. Edzard Ernst blog) considered this review "not just bad but dangerous as well...In view of the fact that even the 5 RCTs [randomized controlled trials] were of poor quality, the first sentence of  this conclusion seems most inappropriate. On the basis of the evidence presented, I feel compelled to urge pregnant women NOT to consent to accept herbal remedies for IOL."

Inflammatory bowel disease - Triantafyllidi et al. 2015. Ann Gastroenterol. 28(2):210-20: "In ulcerative colitis, aloe vera gel, triticum aestivum, andrographis paniculata extract and topical Xilei-san were superior to placebo in inducing remission or clinical response, and curcumin was superior to placebo in maintaining remission; boswellia serrata gum resin and plantago ovata seeds were as effective as mesalazine, whereas oenothera biennis had similar relapse rates as ω-3 fatty acids in the treatment of ulcerative colitis. In Crohn's disease, mastic gum, Artemisia absinthium, and Tripterygium wilfordii were superior to placebo in inducing remission and preventing clinical postoperative recurrence, respectively."

Insomnia - Leach and Page 2015. Sleep Med Rev. 24:1-12: "Four distinct orally administered herbal monopreparations were identified (i.e., valerian, chamomile, kava and wuling). There was no statistically significant difference between any herbal medicine and placebo, or any herbal medicine and active control, for any of the thirteen measures of clinical efficacy."

Irritable bowel syndrome - Hawrelak et al. 2020. Complement Ther Med. 48:102233: "A number of Western herbal medicines show promise in the treatment of IBS. With the exception of peppermint essential oil, Aloe vera, and asafoetida, however, none of the positive trials have been replicated."

Low back pain - Oltean et al 2014.  Cochrane Database Syst Rev. CD004504: "C. frutescens (Cayenne) reduces pain more than placebo. Although H. procumbens [devil's claw], S. alba [white willow], S. officinale L. [comfrey], S. chilensis, and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best."

Menopausal symptoms - Depypere and Comhaire 2014. Maturitas. 77(2):191-4: The review dealt with herbs other than black cohosh. "Randomized controlled trials (RCTs) find that the extracts of Mediterranean pine bark (Pycnogenol(®)), linseed, and Lepididium meyenii (Maca) reduce vasomotor symptoms. The results of RCTs of the hop flavonoid 8-prenylnaringenin are conflicting. Animal and human studies suggest that Dioscorea villosa (Wild yam),and Broccoli may protect against osteoporosis and breast and gynecological cancers but further evidence is required. Linseed may protect against breast cancer but the results are conflicting."

Multiple sclerosis - Mojaverrostami et al. 2018. Adv Pharm Bull. 8(4):575-90: " The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa, Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients...it can be concluded that the anti-inflammatory effect is the main reason of medicinal plants therapeutic effects in MS disease..."

Osteoarthritis - Cameron and Chrubasik 2013. Cochrane Database Syst Rev. CD010538: "Although the mechanism of action of the topical medicinal plant products provides a rationale basis for their use in the treatment of osteoarthritis, the quality and quantity of current research studies of effectiveness are insufficient. Arnica gel probably improves symptoms as effectively as a gel containing non-steroidal anti-inflammatory drug, but with no better (and possibly worse) adverse event profile. Comfrey extract gel probably improves pain, and Capsicum extract gel probably will not improve pain or function at the doses examined in this review."

Psychiatry - Werneke et al. 2006. Br J Psychiatry. 188:109-21: "Potentially useful substances include ginkgo and hydergine as cognitive enhancers, passion flower and valerian as sedatives, St John's wort ...to complement antidepressants."

Smoking cessation - Kitikannakorn et al. 2013. Complement Ther Med. 21(5):557-64: "Three RCTs evaluated oral St. John's wort (SJW) extract (N=289), 2 RCTs evaluated oral mix-herbal tea (N=164), and 1 RCT evaluated inhaled aromatic black pepper (N=48)...Evidences of SJW indicated low percentage in abstinence rate for smoking and its effectiveness was not significantly different from placebo. Studies of mix herbal tea showed a statistically significant effectiveness, compared to placebo, in reducing the number of cigarettes per day, craving scale, and total withdrawal scale but not urinary cotinine excretion. Essential oil of black pepper with a hollow plastic tube significantly reduced craving at 3-h session...Evidence supporting the role of complementary medicines as an anti-smoking is limited."

Viral myocarditis - Liu et al. 2012. Cochrane Database Syst Rev. CD003711: "Some herbal medicines may lead to improvement of ventricular premature beat, electrocardiogram, level of myocardial enzymes, and cardiac function in viral myocarditis. However, these findings should be interpreted with care due to the high risk of bias of the included studies, small sample size, and limited number of trials on individual herbs. Further robust trials are needed to explore the use of herbal medicines in viral myocarditis."


POTENTIAL TOXICITY

Tyler (1989. Hazards of herbal medicine. In: Stalker D, Glymour C. Examining Holistic Medicine. 323-339) noted the following types of hazards:

Some dangerous herbs (from Consumer Reports, May 2004):

“Many herbs commonly injure the liver, accounting for 20% of reported hospitalization for drug-related hepatotoxicity. Liver injury from chemicals develops slowly, manifesting signs between 1 week and 1 month after exposure. Symptoms are generally non-specific and often are difficult to attribute to a specific herb. Hepatotoxicity may be idiosyncratic, as in the case of kava, or intrinsic and dose dependent, as with the pyrrolizidine alkaloids (PA), components of herbs that affect not only humans but also livestock and wildlife. PAs are found in 3% of the world's flowering plants, many of which have been incorporated into TCM [traditional Chinese medicine]” (Grollman and Marcus 2016. EMBO Rep. 17(5):619-25).

Ephreda (ma huang) has been marketed as an appetite suppressant and/or metabolic stimulant. It was sometimes promoted as an alternative to illegal drugs such as “ecstasy.” More recently it has been promoted for use in children with attention deficit hyperactivity disorder. The active component is ephedrine, which can raise blood pressure, cause strokes and heart problems, and have other effects. Ephedra was blamed for at least 54 deaths and hundreds of illnesses from 1993 through 2005. After growing concern over its safety, the FDA banned sale of dietary supplements containing ephedra in 2004 (the ban did not apply to traditional Asian medicines containing ephedra). In 2005, a federal judge ruled that the FDA cannot ban products containing 10 mg or less of ephedra; the status of more potent products (which allegedly would be needed for weight loss benefits) is unclear.

"Upon removal of ephedra-containing products, 'ephedra-free' substitutes—supplements formulated with identical caffeine sources but incorporating an even greater selection of natural (e.g., synephrine, phenylethylamines, theophylline, yohimbine, etc.) and synthetic stimulants (e.g., dimethylamylamine, etc.) - instantly filled the void of their banned predecessors...Today, a wide-range of poorly studied ephedra-free DS are marketed to amateur and professional athletes as 'preworkout' exercise performance enhancers. Despite their 'ephedra-free' claims, these products do not seem to be any safer, especially when combined with vigorous exercise, heat stress, or when taken with prescription stimulants (e.g., methylphenidate, amphetamine) and/or exogenous caffeine sources (e.g., energy drinks/shots)" (Gurley et al. 2018. Clin Pharmacol Ther. 104(3):470-83).

Aristolochia is an herb used in traditional Chinese medicine. Kidney failure in about 100 Belgian women in 1990 and 1991 was found to be due to aristolochic acid in the herb. It has also been linked to urinary tract cancers in Taiwan. Some countries have banned its use, but it continues to be available. Grollman and Marcus (2016. Op. cit.) noted that “we cannot know whether all herbal medicines are safe because only a few have been tested systematically for toxicity or carcinogenicity. As an example, the potent toxic effects associated with the use of Aristolochia species - which came to light only after recent epidemiologic studies vividly demonstrated the health risks of this widely used family of medicinal herbs. This previously unknown toxicity provides a strong argument for more effective regulation of herbal medicine use in developed and developing countries to prevent similar dangers to public health."

Kratom, a currently popular herb used for pain relief and as a stimulant, has attracted attention from the FDA because of its potential dangers (see detailed discussion in the section on kratom below).           

Ang-Lee et al. (2001. JAMA 286(2):208-276) reviewed the hazards of presurgical use of common herbs. “Direct effects include bleeding from garlic, ginkgo, and ginseng; cardiovascular instability from ephedra; and hypoglycemia from ginseng. Pharmacodynamic herb-drug interactions include potentiation of the sedative effect of anesthetics by kava and valerian. Pharmacokinetic herb-drug interactions include increased metabolism of many drugs used in the perioperative period by St. John’s wort.”

A 2002 study found that two herbs used for menopausal symptoms, dong quai and ginseng, stimulated growth of cultured breast cancer cells.

A survey of web sites dealing with ginseng, gingko, and St. John’s wort found that 25% “contained statements that could lead to direct physical harm if acted upon” (Walji et al. 2004. J Med Internet Res. 6(2):e2).

According to a survey by de Souza Silva et al. (2014. Arch Gerontol Geriatr. 59(2):227-33), the herbs most frequently used by the elderly are ginkgo and garlic. "Both of these supplements have the potential to interact with anticoagulants and produce bruising or bleeding problems."

A review by Posadzki et al. (2013. Br J Clin Pharmacol. 75(3):603-18) found that “the majority of SRs [systematic reviews] revealed moderately severe or minor interactions between HMPs [herbal medicinal products] and drugs. Some HMPs, however, do interact with drugs posing severe health threats. Due to the limited quality and scarcity of the primary data, these conclusions should be treated with caution.”

A review by Fasinu and Rapp (2019. Front Oncol. 9:1356) “identified six herbal products namely echinacea, garlic, ginseng, grapefruit juice, milk thistle, and St John's wort, which have shown interactions with chemotherapeutic agents in humans."

Skalicka-Woźniak et al. (2017. Food Chem Toxicol. 108(Pt B):355-64) discussed adulteration of herbal products for weight loss and sexual enhancement with conventional drugs.

Farrington et al. (2019. Acta Paediatr. 108(3):419-22) noted that “Infants and children may be more susceptible to harmful effects [of herbal preparations] due to their immature physiology and metabolic pathways and different dosage requirements.”


SCIENTIFIC CRITIQUE

“By the end of the 19th century, the therapeutic benefits of a number of herbs were recognized, and, in some cases, their active principles were extracted and purified and marketed. However, considering the large number of herbs in use at that time, the list of demonstrable active and effective herbs is remarkably short: ma huang (ephedrine), Digitalis purpura (digoxin), Cinchona bark (quinine), Ipecacuanha (emetine), Opium poppy (morphine), Colchicum (colchicine), and Belladonna (atropine)” (Grollman and Marcus 2016. Op. cit.).

Pharmacologically active chemicals from herbs can be isolated in pure form; these then can be subject to controlled studies of their safety and effectiveness. If a useful drug results, this can then be prepared with high standards of purity and administered in a known dosage, free of possible side effects of other compounds in the herbal preparation.

Herbs may be selected and administered by laypersons, or on the advice of health food store personnel or others without medical expertise.

"The deception inherent to the herbal product industry, in my opinion, is the notion that herbs are something other than drugs. This is closely tied to the naturalistic fallacy: the idea that a substance that is 'natural' (a poorly defined concept) is somehow magically safe and effective" (Novella 2013. Skeptical Inquirer. 37(2):28-9).

Names on products may not indicate which species they come from (particularly for imported herbs)

Plants differ widely in content of effective ingredients, making dosages inconsistent. A 1998 study of St. John's wort products found more than 10-fold differences in the concentrations of the presumed active ingredients (see also below concerning standardization). Similar studies dealing with other herbs have also found wide variations in contents among commercial preparations.

Newmaster and others (2013. BMC Med. 11:222) used genetic analysis called DNA barcoding to test 44 herbal products. They found that 59% "contained DNA barcodes from plant species not listed on the labels...Product substitution occurred in 30/44 of the products tested and only 2/12 companies had products without any substitution, contamination or fillers." However, "Efforts to identify and authenticate a particular plant species within a BDS [botanical dietary supplement] dosage form via DNA-based methods can be unsuccessful as the extraction process may leave behind little viable DNA. Recently, inappropriate characterization of finished BDS dosage forms via DNA fingerprinting by the New York Attorney General's Office produced unnecessary public concern regarding the authenticity of many popular BDS sold in several major retailers" (Gurley et al. 2018. Op. cit.). Tims (2016. J Altern Complement Med. 22(8):588-90) pointed out that "There are additional limitations to plant DNA methods as a quality assurance or regulatory tool. For instance, even when the technique correctly identifies the plant, DNA testing cannot identify the plant part used to make the product. It cannot tell us whether the plant was grown under the right environmental conditions to produce the appropriate phytochemical profile. And because many of the herbs in supplements are botanical extracts, not intact plants, it may not be able to identify the plant ingredients. The method is best applied to non-extracted plant materials and as a complement to other chemical tests. Even identifying plants in unprocessed herbal material can be a challenge."

Some herbal remedies may be spiked with real drugs, or have other herbal products substituted for expensive ones (e.g., ginseng) (one study found that only 25% of commercial ginseng products actually contained ginseng!).

A survey of the top 50 web sites marketing each of 13 common herbs found that "Less than 8% of retail sites provided information regarding potential adverse effects, drug interactions, and other safety information; only 10.5% recommended consultation with a healthcare professional. Less than 3% cited scientific literature to accompany their claims" (Owens et al. 2014. Am J Med. 127(2):109-15).

Herbs may be substituted for effective treatments: “Many oncologists have seen patients with early-stage cancers who eschewed curative conventional care in favor of herbal medicines” (Winslow and Kroll 1998. Arch Int Med. 158(20):2192-9).

“Patients may also continue detrimental behaviors, such as smoking tobacco or drinking large amounts of alcohol, with the rationalization that the herbal remedy they are taking will be protective.” (Ibid.)

Some herbs can interfere with certain laboratory tests based on immunoassays.

A review of the ergogenic properties of ginseng (Bahrke and Morgan 1994. Sports Med. 18(4): 229-48) illustrates the complexities in evaluating some herbal remedies. Ginseng is advocated for enhanced energy in general as well as for numerous specific conditions. Its active ingredients are at least 13 saponins, which can have opposing effects and be present in different amounts in different preparations. This could explain why "...in animal research, hypertensive and hypotensive effects, histamine- and antihistamine-like actions, and both stimulant and depressant activity on the central nervous system (CNS) have been reported." Sengupta et al. (2004. Circulation. 110(10):1219-25) identified one component of ginseng that has an angiogenic effect, and another that has an anti-angiogenic effect.

Manufacturers attempt to control for variability by making standardized preparations, blended to contain consistent amounts of the presumed active ingredients. However, this presumption may be inaccurate. St. John's wort has been standardized to hypericin and pseudohypericin, but some studies suggested that another component, hyperforin, is actually most important. Studies with feverfew suggest that its actions may not be from the commonly presumed active ingredient. A study of echinacea preparations (2003) found that less than half of standardized preparations met the standards on their labels. Even if the active ingredient is standardized, other ingredients may affect its absorption or metabolism.

"Bioavailability, which includes contributions from absorption, intestinal metabolism, and hepatic first pass metabolism, is an important but often overlooked determinant of efficacy of botanical dietary supplements. Only those compounds that cross the intestinal epithelium are likely to produce systemic effects, and lack of absorption might explain why many clinical trials of botanical dietary supplements as well as isolated natural products have shown no pharmacological effects in spite of in vitro studies suggesting otherwise" (van Breemen 2015. Op. cit.).

Ernst and others reviewed NCCAM-funded trials of herbal medicine (2011. Perfusion. 24(3):89-102) and found "a plethora of serious concerns." "None of the RCTs fully described the herbal treatment according to the CONSORT guidelines. Several trials seemed not to be registered. In addition, there were numerous other concerns including small sample sizes, wrong statistical evaluations and lack of reporting of adverse effects or safety parameters."

Concerning the extreme variability in the components of herbal remedies, Pandolfi and Zilletti (2012. Eur J Intern Med. 23(4):330-2) wrote that it “hinders also this type of evaluation [randomized controlled trials] since we cannot possibly perform a clinical trial for every plant subspecies, every part of it (leaves, stem, roots), every crop. And, as Karl Popper made clear, what cannot be tested is not experimental science - and therefore not acceptable medicine, since medicine is just experimental science.”

"Part of the problem is that negative studies are too easy to dismiss. In every case the supplement industry finds some reason to minimize the implications of the studies showing their products do not work, instead preferring to cherry pick small and unreliable studies with positive results. No study can possibly address every possible permutation of how an herb can be used...Of course, this logic works both ways: if it’s so difficult to find the right preparation for the right condition, then how do they justify selling highly variable products to the general population with broad claims?" (Novella 2013. Skeptical Inquirer. 37(2):28-9).

Nababizadeh et al. (2018. Urology. 112:145-50) reviewed herbal supplements for prostate enlargement. Top-selling products had an average of eight ingredients, most of which had no evidence of effectiveness.


NONSCIENTIFIC ASPECTS

Reliance on undocumented claims, sometimes dating back centuries

Claim that herbs are safe and effective because they have been used for thousands of years

Reliance on anecdotal evidence

Reference to mystical concepts of "energy"

Claims of conspiracy by medical establishment and pharmaceutical industry to suppress use of herbs

Unsupported claim that the whole herb is more effective and less toxic than its isolated components. This is related to idea that the herb is present for human benefit (scientific view: plant makes compounds for its own benefit; occasionally one is of pharmacologic use in humans). As Pandolfi and Zilletti (2012. Op. cit.) wrote, “The main rationale of herbal medicine is more cultural than scientific and consists in the ancient belief that nature is particularly friendly to humans who are considered the purpose of creation.”

Related to this belief is the "Doctrine of Signatures," the ancient magical idea that the shape or appearance of an herb guides its application (e.g., eyebright, having a spotted flower and resembling an eye, for treatment of eye diseases).

Concerning the idea that different constituents of an herb work together, Tyler (1999. False tenets of paraherbalism. Quackwatch) wrote: “Synergism occasionally occurs, but for every case where a desirable action is enhanced, there are several where undesirable actions are produced. For example, cinchona bark contains some 25 closely related alkaloids, but the only one recognized as useful in the treatment of malaria is quinine. A person who took powdered cinchona bark would also ingest the alkaloid quinidine, a cardiac depressant, and cinchotannic acid, which would induce constipation.”

Claim that a natural chemical is superior to its synthetic counterpart


SOME POPULAR HERBS

[Note: some items used as food or spices, as well as some individual chemicals derived from plants, are covered in dietary supplements handout. Some items used only topically are not included.]


Aloe vera (Aloe vera, A. barbadensis)

Uses: topically for burns, wounds, and other skin conditions; orally as a laxative and for arthritis and fever

Possible toxic effects: intestinal cramps, diarrhea. May lower blood glucose so caution is needed for individuals with diabetes. “Aloe vera can cause a drop in the blood’s potassium level, which in turn can lead to heart rhythm problems, as well as complications in heart patients taking the drug digoxin” (Anon 2013. Heart trouble? 15 Herbal remedies to avoid. Health.com).

Review: Dick et al. 2016. J Altern Complement Med. 22(6):450-7: “These results support the use of oral aloe vera for significantly reducing FBG [fasting blood glucose] (46.6 mg/dL) and HbA1c [hemoglobin A1c] (1.05%). Further clinical studies that are more robust and better controlled are warranted to further explore these findings.” However, Ernst (2016 Dec 21. Edzard Ernst blog) stated that the review had serious flaws and was “of unacceptably poor quality.” “If some of these patients are sufficiently gullible to follow the conclusions of this paper, they might be dead within a matter of days. This makes this article one of the most dangerous papers that I have seen in the ‘peer-reviewed’ literature of alternative medicine.”

Notes: "In 2002, the FDA required that all OTC aloe laxative products be removed from the U.S. market or reformulated because the companies that manufactured them did not provide the safety data necessary for continued approval. There’s some evidence that the topical use of aloe products might be helpful for symptoms of certain conditions such as psoriasis and certain rashes. There’s not enough high-quality scientific evidence to show whether topical use of aloe helps to heal wounds. There’s not enough scientific evidence to support aloe vera for any of its other uses" (National Center for Complementary and Integrative Health 2016. Aloe vera). In 2019 the FTC took action against marketers for claiming their aloe vera supplements “were effective treatments for a range of conditions affecting seniors.”


Arnica (various species of Arnica)

Uses: pain, bleeding, especially after surgery

Possible toxic effects: poisonous if taken by mouth. Topical use is considered unsafe in pregnancy and lactation. Possible allergic reactions if allergic to ragweed and related plants. Should not be used on broken skin.

Review: Brito et al. 2013. J Musculoskeletal Pain. 22(2):216-23 (pain, swelling, and bruises): “The efficacy of Arnica in doses of 10% and below is not supported by the available evidence. More research is needed to determine if higher doses would be effective and remain safe.”

Notes: The plant material is applied topically. Also used in the form of a homeopathic remedy, which cannot provide any benefit.


Ashwagandha (Indian ginseng, poison gooseberry, winter cherry; Withania somnifera)

Uses: as an "adaptogen" and for numerous other purposes

Presumed active agents: "The main phytochemical constituents are withanolides - which are triterpene lactones - withanolides, withaferin A, alkaloids, steroidal lactones, tropine, and cuscohygrine. Some 40 withanolides, 12 alkaloids, and numerous sitoindosides have been isolated" (Wikipedia 2020. Withania somnifera).

Possible toxic effects: likely unsafe during pregnancy, can lower blood sugar, might decrease blood pressure, can irritate ulcers. Should be avoided by individuals with autoimmune disease or thyroid condition.

Notes: used in Ayurvedic medicine. "Ashwagandha has a lot of uses. But so far, there isn't enough information to judge whether it is effective for any of them" (MedlinePlus 2019. Ashwagandha).


Astragalus (Astragalus membranaceus, A. mongholicus, and other species)

Uses: "for many conditions, including for diarrhea, fatigue, anorexia, upper respiratory infections, heart disease, hepatitis, fibromyalgia, and as an adjunctive therapy for cancer" (NCCIH 2016. Astragalus).

Possible toxic effects: diarrhea, lowering blood glucose, may interact with medications that suppress immune system. "Some astragalus species, usually not found in dietary supplements, can be toxic. Several species that grow in the United States contain the neurotoxin swainsonine and have caused 'locoweed' poisoning in animals. Other species contain potentially toxic levels of selenium" (Ibid.).

Notes: "There are no high-quality studies in people of astragalus for any health conditions" (Ibid.). Used in traditional Chinese medicine.


Barberry (Berberis vulgaris)

Uses: “anti-bacterial, anti-carcinogenic, anti-histaminic, anti-hyperglycaemic, anti-oxidant, anti-inflammatory, anti-hypertensive, and lipid lowering agent” (Hadi et al. 2019. Complement Ther Med. 43:117-24).

Presumed active agents: berberine, berbamine, palmatine, oxyacanthine, malic acid, berberubin

Reviews:


Belladonna (Atropa belladonna)

Uses: "Though widely regarded as unsafe, belladonna is taken by mouth as a sedative, to stop bronchial spasms in asthma and whooping cough, and as a cold and hay fever remedy. It is also used for Parkinson's disease, colic, inflammatory bowel disease, motion sickness, and as a painkiller. Belladonna is used in ointments that are applied to the skin for joint pain, pain along the sciatic nerve, and general nerve pain. Belladonna is also used in plasters (medicine-filled gauze applied to the skin) for mental disorders, inability to control muscle movements, excessive sweating, and asthma. Belladonna is also used as suppositories for hemorrhoids" (MedlinePlus 2019. Belladonna).

Possible toxic effects: Unsafe when taken by mouth. Produces numerous effects on the nervous system. May aggravate numerous health conditions.


Berberine is a chemical found in some herbs. See barberry and goldenseal for reviews.


Bilberry (European blueberry, Vaccinium myrtillus and related species)

Uses: diarrhea, scurvy, infections, burns, diabetes, urinary tract infections, eye problems

Possible toxic effects: "Bilberry fruit is considered safe when consumed in amounts typically found in foods, or as an extract in recommended doses for brief periods of time. Bilberry leaves may be unsafe when taken orally (by mouth) in high doses or for long periods of time" (NCCIH 2016. Bilberry).  Increased risk of bleeding if taking warfarin.

Notes: "There’s not enough scientific evidence to support the use of bilberry for any health conditions" (NCCIH 2016. Bilberry). “Some claim that bilberry fruit improves night vision, but clinical studies have not shown this to be true” (NCCAM 2006. Bilberry).


Bitter melon (bitter apple, bitter gourd, karela; Momordica charantia)

Uses: diabetes, stomach and intestinal problems, and many other conditions

Presumed active agents: momordicins

Possible toxic effect: upset stomach

Reviews:

Notes: "Bitter melon is a vegetable used in India and other Asian countries. The fruit and seeds are used to make medicine...there is no good scientific evidence" in support of its use (MedlinePlus 2019. Bitter melon). “Two RCTs have evaluated the effects of bitter melon in patients with type 2 DM [diabetes mellitus]...There is no evidence to support the use of bitter melon” (Nahas and Moher 2009. Can Fam Physician. 55(6):591-6).


Bitter orange (Citrus aurantium)

Uses: "heartburn, nasal congestion, weight loss, appetite stimulation or suppression, and athletic performance. Bitter orange is also applied to the skin for pain, bruises, infections, and bed sores" (NCCIH 2019. Bitter orange).

Presumed active agent: p-synephrine

Possible toxic effects: possibly raises blood pressure and heart rate

Review: Stohs et al. 2012. Int J Med Sci. 9(7):527-38: “In general, bitter orange extract alone (p-synephrine) or in combination with other herbal ingredients did not produce significant adverse events...p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks. Longer term studies are needed to further assess the efficacy of these products and affirm their safety under these conditions.”

Notes: use for weight loss is discussed in the article on dietary supplements. Has been substituted for ephedra. Banned as a stimulant by the NCAA.


Black cohosh (Actaea racemosa = Cimicifuga racemosa)

Uses: premenstrual syndrome, dysmenorrhea, postmenopausal symptoms, breast enhancement, induction of labor, arthritis, musculoskeletal pain, fever

Presumed active agents: “A partial list of active compounds includes the isoflavone formononetin, isoferulic, caffeic, salicylic, and fukinolic acids. There are also miscellaneous fatty acids, tannins, and sugars.  Phytosterin and resins that include Cimicifuga and triterpene glycosides are also present” (Wobser and Takov 2019. Black cohosh. StatPearls).

Presumed mechanisms of action: “Most evidence points to several different mechanisms of action. Some researchers have shown evidence that it may exert its effects centrally, through alterations in the serotonin pathways. Others have demonstrated its ability to act as an antioxidant or anti-inflammatory. Others still have shown that it acts as a selective estrogen receptor modulator in the same manner as Tamoxifen. The only things that can be said with certainty is that is [sic] is not completely understood and appears to have multiple potential mechanisms of action” (Ibid.).  

Possible toxic effects: gastrointestinal disturbances, hypotension, nausea, headaches, drowsiness, rashes. Possible interference with cancer drugs such as tamoxifen, as well as with glyburide and statins. May decrease iron absorption. Possibly unsafe for women who have had breast cancer. “The US Pharmacopeia has determined that black cohosh may be responsible for more than 30 cases of liver damage. Worldwide, there have been 83 reports of liver damage associated with the use of black cohosh...Since some compounds in black cohosh have estrogenic activity, it would be prudent to avoid its use when there is a history of breast cancer, endometrial cancer, thromboembolic disorders, undiagnosed vaginal bleeding, endometriosis, and fibroids” (Ibid.).

Reviews:

Notes: It has "seen increased use in women suffering from breast cancer. Its increased use may in part be because of studies from the Women’s Health Initiative showing traditional hormone replacement therapy increased the risk of breast cancer and negative cardiovascular consequences" (Furhad and Bokhari 2020. Herbal supplements. StatPearls). "Studies that tested black cohosh for menopause symptoms have had inconsistent results. The overall evidence is insufficient to support using black cohosh for this purpose.

There are not enough reliable data to show whether black cohosh is effective for other uses...should not be confused with blue cohosh (Caulophyllum thalictroides), which has different effects and may not be safe" (NCCIH 2016. Black cohosh). “Studies do not show any consistent effect on the follicle-stimulating hormone, luteinizing hormone, or estrogen.  Studies have shown no consistent effect on tissues of the female reproductive tract. No consistent effect was seen in either a histologic or functional sense” (Wobser and Takov 2019. Op. cit.).


Black cumin - see Nigella


Blessed thistle (Cnicus benedictus)

Uses: "prepared as a tea and used for loss of appetite and indigestion; and to treat colds, cough, cancer, fever, bacterial infections, and diarrhea. It is also used as a diuretic for increasing urine output, and for promoting the flow of breast milk in new mothers" (MedlinePlus 2019. Blessed thistle).

Presumed active agents: tannins

Possible toxic effects: stomach irritation, vomiting, allergic reactions, possibly unsafe in pregnancy and breast feeding.

Notes: insufficient evidence of effectiveness for any condition.


Blue cohosh (Caulophyllum thalictroides)

Uses: "stimulating the uterus and starting labor; starting menstruation; stopping muscle spasms; as a laxative; and for treating colic, sore throat, cramps, hiccups, epilepsy, hysterics, inflammation of the uterus, infection of the female organs (pelvic inflammatory disease), over-growth of uterine tissue (endometriosis), and joint conditions" (WebMD 2018. Blue cohosh).

Possible toxic effects: "There are three case reports in the scientific literature that blue cohosh taken at the time of delivery may cause; 1) perinatal stroke, 2) acute myocardial infarction, profound congestive heart failure and shock and 3) severe multi-organ hypoxic injury. There is one case report that blue cohosh possesses abortifacient properties. There is in vitro evidence that blue cohosh may have teratogenic, embryotoxic and oxytoxic effects. In lactation, the safety of blue cohosh is unknown...Based on the available scientific information, blue cohosh should; 1) be used with extreme caution during pregnancy, 2) be used only under medical professional supervision and 3) not be available to the public as an over-the-counter product" (Dugoua et al. 2008.  Can J Clin Pharmacol. 15(1):e66-73).

Notes: "According to a survey of midwives in the United States, approximately 64% of midwives reported using blue cohosh as a labour-inducing aid" (Ibid.).


Boswellia serrata (Indian frankincense)

Uses: "treatment of many inflammatory conditions, such as osteoarthritis and rheumatoid arthritis" (Lampl et al. 2012. Cephalalgia. 32(9):719-22).

Presumed active agents: pentacyclic triterpene acids, particularly boswellic acid

Presumed mechanisms of action: anti-inflammatory and analgesic effects via "inhibiting cytokines and leukocyte activity" (Ibid.).

Review: Cameron and Chrubasik 2014. Cochrane Database Syst Rev. CD002947 (osteoarthritis): “Several other medicinal plant products, including extracts of Boswellia serrata, show trends of benefits that warrant further investigation in light of the fact that the risk of adverse events appear low.”


Butterbur (Petasites hybridus)

Uses: "urinary tract symptoms, stomach upset, headaches including migraines, allergic rhinitis (hay fever), and other conditions" (NCCIH 2016. Butterbur).

Presumed active agents: "eremophilane sesquiterpenoid substances, specifically petasin, isopetasin, S-petasin, and iso-S-petasin. Also found in the extracts of butterbur are volatile oils, flavonoids, tannins, and pyrrolizidine alkaloids" (Sutherland and Sweet 2010. Am J Health-System Pharm. 67(9):705-11).

Presumed mechanisms of action: "The active components of butterbur, particularly isopetasin, inhibit the lipoxygenase pathway and leukotriene synthesis, key processes in the activation of inflammation. Petasin and its analogues also decrease the activation of mast cells, which results in decreased release of leukotrienes and histamine into the circulation. Isopetasin may also contribute to the antiinflammatory properties of butterbur by enhancing prostaglandin metabolism...The antispasmodic properties of butterbur...are attributed to its petasin constituents, as they cause smooth muscle and vascular wall relaxation. Petasins block calcium influx into the smooth muscle cells via voltage-dependent calcium channels" (Ibid.).

Possible toxic effects: "belching, headache, itchy eyes, diarrhea, breathing difficulties, fatigue, and drowsiness" (NCCIH); allergic reactions. Pyrrolizidine alkaloids in unprocessed plant "can cause liver damage and can result in serious illness. Only butterbur products that have been processed to remove PAs and are labeled or certified as PA-free should be used" (NCCIH). "Patients who have hypersensitivity reactions or allergies to other plants in the Asteraceae family (e.g., ragweed, marigolds, daisies, chrysanthemums) should use caution when taking butterbur, as there is the potential for cross-reactivity. No allergic reactions, however, have been reported. Pregnant and lactating women should not take butterbur, as its safety has not been established in these populations...The use of butterbur should not be combined with that of other herbal products containing pyrrolizidine alkaloids to avoid any potential additive toxicity. Since pyrrolizidine alkaloids are metabolized to toxic metabolites by CYP3A4 [cytochrome P450 3A4], concomitant administration of butterbur and 3A4 inducers (e.g., St. John’s wort, carbamazepine, phenytoin, rifampin, phenobarbital) should be avoided, as this may enhance toxicity. Butterbur should not be used in combination with medications or herbs (e.g., bittersweet) that have anticholinergic properties because of the potential for additive therapeutic or adverse effects" (Sutherland and Sweet 2010. Op. cit.).

Review: Sutherland and Street 2010. Op. cit.: "Evidence from clinical trials suggests that butterbur is an effective therapy for migraine prevention in adults, with 75 mg twice daily potentially being superior to 50 mg twice daily. Evidence from clinical trials in children is limited largely by study design; however, butterbur may be efficacious for migraine prevention in pediatrics."

Notes: "Based on two high-quality studies, the American Academy of Neurology and the American Headache Society have endorsed the use of a butterbur extract made from underground parts of the plant, like the root or rhizome, to reduce the frequency of migraines. Some studies of butterbur root or leaf extracts suggest that they may be helpful for symptoms of hay fever (allergic rhinitis). Butterbur has not been proven to be helpful for allergic skin reactions or asthma...Commercial butterbur products that contain extracts from the root, rhizome (underground stem), or leaves of the plant are available. Raw, unprocessed butterbur products, such as teas, should not be used because they contain harmful substances" (NCCIH).


Cascara sagrada (Rhamnus purshiana)

Uses: laxative

Presumed active agents: "The chemicals possibly responsible for the laxative effect are the hydroxyanthracene glycosides, which include cascarosides A, B, C, and D" (Wikipedia 2020. Rhamnus purshiana).

Presumed mechanism of action: "The hydroxyanthracene glycosides may trigger peristalsis by inhibiting the absorption of water and electrolytes in the large intestine, which increases the volume of the bowel contents, leading to increased pressure" (Ibid.).

Possible toxic effects: Long-term use (more than one or two weeks) should be avoided. Danger of dehydration and low levels of electrolytes. Should not be used when breast feeding. Should not be used in combination with drugs that can cause loss of potassium.

Notes: Had been approved by FDA as over the counter drug for constipation, but manufacturers did not provide requested safety and effectiveness data, so this was withdrawn in 2002; it is now sold as a dietary supplement instead of a drug. MedlinePlus (2019. Cascara sagrada) rates as possibly effective for constipation; insufficient evidence for other conditions.


Cat’s Claw (Uncaria tomentosa, U. guianensis)

Uses: for many disorders, including viral infections, Alzheimer's, arthritis, cancer, ulcers, and menstrual problems.

Presumed active agents: "There are two chemotypes of U. tomentosa that differ markedly in their patterns of alkaloids present in the root bark. One chemotype primarily contains the pentacyclic oxindole alkaloids pteropodine, isopteropodine, mitraphylline, isomitraphylline, uncarine F, and speciophylline. The other chemotype primarily contains the tetracyclic oxindole alkaloids rhynchophylline and isorhynchophylline. Although a particular plant may contain either tetracyclic or pentacyclic oxindole alkaloids predominantly, both types of alkaloids can concomitantly occur in the same plant. The glycoside quinovic acid has been isolated from both species. Polyhydroxylated triterpenes and steroids (e.g., β-sitosterol, stigmasterol, campesterol) occur in U. tomentosa" (Erowele and Kalejaiye 2009. Am J Health-Syst Pharm. 66(11):992-5). "Most investigators attribute the biological effects of this plant to the POAs [pentacyclic oxindole alkaloids]" (de Paula et al. 2015.  J Altern Complement Med. 21(1):22-30).

Presumed mechanisms of action: alkaloids "are purported to exhibit various pharmacologic activities, including antiinflammatory, antiviral, antioxidant, immuostimulating, anti-rheumatic, and anticancer properties" (Erowele and Kalajaiye 2009. Op. cit.). Induction of apoptosis and reduction of NF-κB have also been proposed. Other possible effects are inhibition of viral infections by quinovic acid glycosides, as well as antioxidant, anti-inflammatory, and antiviral effects of procyanidins.

Possible toxic effects: "Few side effects have been reported for cat’s claw when taken in small amounts.  Women who are pregnant or trying to become pregnant should avoid using cat’s claw because of its past use for preventing and aborting pregnancy" (NCCIH 2016. Cat's claw).

Review: Erowele and Kalejaiye 2009. Op. cit.: "Because of the lack of adequate clinical trials, more studies are needed to establish a place in therapy for cat’s claw."

Notes: "Cat’s claw is a woody vine that grows wild in the Amazon rainforest and other tropical areas of Central and South America. Its thorns resemble a cat’s claws...There’s no conclusive scientific evidence based on studies in people that supports using cat’s claw for any health purpose" (NCCIH).


Chamomile (German chamomile; Matricaria recutita, Chamomilla recutita) (see also Roman chamomile below)

Uses: "sleeplessness, anxiety, and gastrointestinal conditions such as upset stomach, gas, and diarrhea. It is also used topically for skin conditions and for mouth sores resulting from cancer treatment (NCCIH 2016. Chamomile). Other uses include "hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers...rheumatic pain and hemorrhoids" (Srivastava et al. 2010. Mol Med Rep. 3(6):895-901).

Presumed active agents: "Approximately 120 secondary metabolites have been identified in chamomile, including 28 terpenoids and 36 flavonoids. The principal components of the essential oil extracted from the German chamomile flowers are the terpenoids a-bisabolol and its oxide azulenes including chamazulene and acetylene derivatives" (Ibid.).

Presumed mechanisms of action: "One of chamomile’s anti-inflammatory activities involve the inhibition of LPS-induced prostaglandin E(2) release and attenuation of cyclooxygenase (COX-2) enzyme activity without affecting the constitutive form, COX-1" (Ibid.).

Possible toxic effects: allergic reactions, potential for interactions with some drugs

Review: Srivastava et al. 2010. Op. cit.: "Establishing whether or not therapeutic effects of chamomile are beneficial to patients will require research and generation of scientific evidence."

Notes: Results are only preliminary or in combination with other herbs.


Chasteberry (Vitex agnus-castus)

Uses: menstrual problems, menopausal symptoms, infertility, other

Presumed active agents: "The berry of the chaste tree contains a number of active constituents: flavonoids (i.e., casticin, kaempferol, orientin, quercetagetin, and isovitexin), iridoid glycosides (i.e., agnuside and aucubin), and essential oils (i.e., limonene, cineol, pinene, and sabinene)" (Roemheld-Hamm 2005. Am Fam Physician. 72(5):821-4).

Presumed mechanism of action: "Chasteberry shows central dopaminergic activity in vitro and in vivo. This dopaminergic effect inhibits basal- and thyrotropin-releasing hormone–stimulated prolactin release. Chasteberry’s therapeutic effects are attributed to its indirect effects on various hormones, especially prolactin and progesterone. This hormonal effect appears to be dose-dependent: low doses of extract have resulted in decreased estrogen levels and increased progesterone and prolactin levels, possibly caused by an inhibition of the release of follicle-stimulating hormone (FSH) and stimulation of luteinizing hormone (LH) levels. However, in some studies of persons receiving higher doses, FSH and LH levels remained unchanged, while prolactin release was decreased. These effects may explain why lower doses of the herb might stimulate breast milk production, whereas higher doses seem to have the opposite effect" (Ibid.).

Possible toxic effects: "Women on birth control pills or hormone replacement therapy, or who have a hormone-sensitive condition (such as breast cancer) should not use chasteberry. People taking dopamine-related medications, such as certain antipsychotic drugs and Parkinson’s disease medications should avoid using chasteberry" (NCCIH 2016. Chasteberry).

Reviews:

Notes: Preliminary evidence of benefit for premenstrual problems, no evidence for menopausal symptoms.


Curcumin - see turmeric


Dandelion (Taraxacum officinale)

Uses: "Dandelion has a long history of use for problems of the liver, gallbladder, and bile ducts. Today, dandelion as a dietary supplement is used as a blood 'tonic,' as a diuretic, for minor digestive problems, and for other purposes" (NCCIH 2016. Dandelion).

Presumed mechanisms of action: “Dandelion contains chemicals that may increase urine production, prevent crystals from forming in the urine, and decrease swelling (inflammation)” (WebMD 2018. Dandelion).

Possible toxic effects: allergic reactions

Notes: "There’s no compelling scientific evidence supporting the use of dandelion for any health condition" (NCCIH).


Devil's claw (Harpagophytum procumbens)

Uses: atherosclerosis, "arthritis, gout, muscle pain (myalgia), back pain, fibromyalgia, tendonitis, chest pain, gastrointestinal (GI) upset or heart burn, fever, and migraine headache...difficulties in childbirth, menstrual problems, allergic reactions, loss of appetite, and kidney and bladder disease" (MedlinePlus 2019. Devil's claw).

Presumed active agents: harpagoside and other iridoids

Possible toxic effects: diarrhea, "nausea, vomiting, stomach pain, headaches, ringing in the ears, loss of appetite, and loss of taste. It can also cause allergic skin reactions, menstrual problems, and changes in blood pressure" (MedlinePlus).

Reviews:

Notes: Possibly effective for back pain and osteoarthritis; insufficient evidence for other uses (MedlinePlus).


Dong quai (Angelica sinensis)

Uses: menstrual and menopausal problems, migraine, other

Possible toxic effects: increased risk of sunburn. Estrogenic effects make possibly unsafe for some individuals. May interfere with blood clotting.

Review: Wong et al. 2009. Gynecol Endocrinol. 25(3):166-74: "appears not to be efficacious for relieving hot flushes."

Notes: According to MedlinePlus (2019. Dong quai) there is insufficient evidence to rate effectiveness for any condition.


Echinacea (coneflower) (Echinacea purpurea, E. angustifolia, E. pallida)

Uses: prevent and treat cold and flu symptoms; general immune enhancement

Presumed active agents: "Most commercially available echinacea products derive primarily from 2 species, Echinacea purpurea and E. angustifolia, and can be divided into 2 general categories: stabilized fresh juice of aerial parts of E. purpurea, which is rich in such hydrophilic derivatives as polysaccharides and glycoproteins, and an aqueous-ethanolic extract of root material from E. angustifolia or E. purpurea that is richer in lipophilic constituents, such as alkamides. Other potentially active constituents, such as echinacoside; cynarin; and caffeic, caftaric, cichoric, and chlorogenic acids, are found in various concentrations among the different formulations" (Barett et al. 2010. Ann Intern Med. 153(12):769-77).

Presumed mechanisms of action: proliferation of macrophages and other immune cells, enhanced cytokine production and phagocytic activity; antiviral and antibiotic effects

Possible toxic effects: possible immunosuppression and hepatotoxicity with long-term use; little toxicity if taken orally, but several risks if injected. Severe allergic reactions have been reported. Gastrointestinal side effects were common in clinical trials. Rashes observed in trial with children. May interfere with protease inhibitors for HIV.

Reviews:

Notes: second-highest herb in 2017 sales ($84 million). "Taking echinacea after you catch a cold has not been shown to shorten the time that you’ll be sick. Taking echinacea while you’re well may slightly reduce your chances of catching a cold. However, the evidence on this point isn’t completely certain" (NCCIH 2016. Echinacea).


Elderberry - see European elder


Eleuthero - see Siberian ginseng


Ephedra - see discussion in "Potential toxicity" above (p. 6).


Essiac is discussed in the article on cancer therapies (CANCER). "Essiac and Flor Essence are herbal tea mixtures that have been used as anticancer treatments. They have been used to treat other health conditions also, including diabetes, AIDS, and gastrointestinal diseases" (National Cancer Institute 2015. Essiac/Flor Essence (PDQ®)–Patient Version).


Eucalyptus (Eucalyptus globulus and other species)

Uses: "asthma, bronchitis, plaque and gingivitis, head lice, toe nail fungus, and many others" (MedlinePlus 2019. Eucalyptus).

Presumed mechanisms of action: “Eucalyptus leaf contains chemicals that might help control blood sugar. It also contains chemicals that might have activity against bacteria and fungi. Eucalyptus oil contains chemicals that might help pain and inflammation. It might also block chemicals that cause asthma” (WebMD 2020. Eucalyptus).

Possible toxic effects: oil is likely unsafe for children, possibly unsafe if applied to skin without dilution, likely unsafe if taken orally without dilution. Possible interactions with many drugs.

Notes: no good evidence in support of any use (MedlinePlus)


European elder (black elder, elderberry) (Sambucus nigra)

Uses: flu, colds, fever, constipation, sinus infections, pain, swelling, coughs, skin conditions

Presumed active agents: anthocyanins

Possible toxic effects: "The leaves, stems, raw and unripe berries, and other plant parts of the elder tree contain a toxic substance and, if not properly prepared, may cause nausea, vomiting, and severe diarrhea. Because the substance may also be present in the flower, consuming large amounts of the flower might be harmful" (NCCIH 2016. European elder).

Notes: As yet no strong evidence of benefit. "The research on elderberry for colds and flu is promising, but better evidence is needed" (Hall 2019 Dec. 31. Science-Based Medicine blog).


European mistletoe (Viscum album)

Uses: " seizures, headaches, and arthritis. Today, mistletoe is used in Europe as a treatment for cancer" (NCCIH 2016. European mistletoe).

Possible toxic effects: "Mistletoe berries and leaves can cause serious harmful effects when taken orally.

Injected mistletoe extract may cause soreness and inflammation at the injection site, headache, fever, and chills" (NCCIH).

Notes: Mistletoe as a cancer therapy is promoted by anthroposophic medicine, and marketed as Iscador (see the article on cancer therapies).


Fenugreek (Trigonella foenum-graecum)

Uses: increase milk supply during lactation; treatment of diabetes, hyperlipidemia, arthritis, hypothyroidism, hot flashes, dysmenorrhea, infertility

Presumed active agents: diosgenin, 4-hydroxyisoleucine

Possible toxic effects: considered unsafe to use during pregnancy; diarrhea, worsening of asthma.  Increased risk of bleeding if taking warfarin.

Reviews:

Notes: "A few small studies found that fenugreek may help lower blood sugar levels in people with diabetes (generally type 2), but the evidence is weak. Some studies suggest - but haven’t proven - that fenugreek may increase milk production in women who are breastfeeding. There isn’t enough scientific evidence to support the use of fenugreek for any health condition" (NCCIH 2019. Fenugreek).


Feverfew (Tanacetum parthenium, Chrysanthemum parthenium, Matricaria parthenium)

Uses: "Historically, people have used feverfew for fevers, headaches, constipation, diarrhea, difficulty in labor, and dizziness. Today, people use feverfew as a dietary supplement for migraine headache prevention, problems with menstruation, rheumatoid arthritis, psoriasis, allergies, asthma, tinnitus (ringing or roaring sounds in the ears), dizziness, nausea, vomiting, and for intestinal parasites. Topically, people use it as a skin cleanser to reduce or prevent skin infections and for toothaches" (NCCIH 2019. Feverfew).

Presumed active agents: parthenolide, monoterpenes

Presumed mechanisms of action: inhibition of prostaglandin production, inhibition of serotonin release from platelets, spasmolytic effects on cerebral vessels

Possible toxic effects: "Side effects can include nausea, digestive problems, and bloating; if the fresh leaves are chewed, sores and irritation of the mouth may occur. People who take feverfew for a long time and then stop taking it may have difficulty sleeping, headaches, anxiety, and stiff and painful muscles. Do not take feverfew while pregnant because it may affect uterine contractions. Handling the plant may cause skin irritation" (NCCIH).

Reviews:

Notes: "Some research suggests that feverfew may help to prevent migraine headaches, but results have been mixed. However, evidence-based guidelines from the American Academy of Neurology and the American Headache Society suggest that a feverfew extract may be effective and should be considered for migraine prevention. There’s not enough evidence to know if feverfew helps other conditions" (NCCIH).


Ginger (Zinziber officinale)

Uses: reduce nausea; reduce inflammation, such as in arthritis; hypoglycemic effects

Presumed active agents: gingerols, shogaols, paradols

Presumed mechanisms of action: inhibition of serotonin receptors; increased GI motility, affecting signals to central nervous system; vagal stimulation leading to decreased blood pressure and heart rate

Possible toxic effects: heartburn, abdominal discomfort. May interact with blood thinners.

Reviews:

Notes: "Some evidence indicates that ginger may help relieve pregnancy-related nausea and vomiting. Ginger may help to control nausea related to cancer chemotherapy when used in addition to conventional anti-nausea medication. It’s unclear whether ginger is helpful for postsurgery nausea, motion sickness, rheumatoid arthritis, or osteoarthritis" (NCCIH 2016. Ginger).


Ginkgo biloba (maidenhair tree)

Uses: improve circulation: treat stroke, improve memory, lessen Alzheimer's and age-associated dementia; treat heart disease, impotence, blindness, intermittent claudication, tinnitus, brain injury, stroke, other

Presumed active agents: flavonoids, proanthocyanidins, terpenoids (ginkgolides, bilobalide), other

Presumed mechanisms of action: promote vasodilation and improve blood flow to brain; antioxidant effects (flavonoids); platelet-activating factor antagonists (ginkgolides)

Possible toxic effects: may inhibit clotting, cause GI disturbance, headache, nausea, vomiting, allergic reactions. May interact with several drugs, especially increased bleeding risk when taken with warfarin.

Reviews:

Notes: widely used in Europe. EGb 761 is a standardized extract, produced in Germany, that has been used in many studies. "There’s no conclusive evidence that ginkgo is helpful for any health condition. Ginkgo doesn’t help prevent or slow dementia or cognitive decline, according to studies, including the long-term Ginkgo Evaluation Memory Study, which enrolled more than 3,000 older adults...There’s no strong evidence that ginkgo helps with memory enhancement in healthy people, blood pressure, intermittent claudication, tinnitus, age-related macular degeneration, the risk of having a heart attack or stroke, or with other conditions" (NCCIH 2016. Ginkgo).


Ginseng (various species of the genus Panax, such as P. ginseng (Korean ginseng) and P. qinquefolius (American ginseng))

Uses: enhanced energy and well-being, treat erectile dysfunction, enhance learning, enhance immune function, sedative, demulcent, other

Presumed active agents: ginsenosides (a type of saponin), polysaccharides

Presumed mechanisms of action: vasodilation; antioxidant; increased production of acetylcholine; activate macrophages and natural killer cells. "...ginsenosides act by binding to steroid hormone receptors, such as androgen, estrogen, and glucocorticoid receptors, to modulate gene expression...ginsenosides can also function through transcription-independent, nongenomic activation of signaling cascades, such as phosphoinositide 3-kinase/Akt, adenosine monophosphate-activated protein kinase, and calcium signaling that occurs outside the nucleus. Ginsenosides are also implicated in ion channel regulation, including voltage-dependent and ligand-gated ion channels, for the control of cardiovascular function and hypertension. Recent developments have also revealed ginsenosides to be an important regulator of microRNAs (miRNAs)" (Choi et al. 2015. Science.350(6262) Suppl:S54-6). "In the prevention of fatigue, ginseng was shown to increase recovery of creatinine kinase, decrease IL-6 and increase insulin sensitivity...Ginsenosides and their metabolites are known to modulate signaling pathways of metastasis, angiogenesis, inflammation, oxidative stress and stem/progenitor-like properties in breast cancer cells" (Furhad and Bokhari 2020. Herbal Supplements. StatPearls).

Possible toxic effects: nervousness, excitation, headache, insomnia, palpitations, hypoglycemia, nausea, diarrhea, itching; estrogenic effects, vaginal bleeding. Reduces effects of warfarin and some other drugs. NCCIH (2016. Asian ginseng) states "Short-term use of Asian ginseng in recommended amounts appears to be safe for most people. However, questions have been raised about its long-term safety, and some experts recommend against its use by infants, children, and women who are pregnant or breastfeeding...Some evidence suggests that Asian ginseng might affect blood sugar and blood pressure."

Reviews:

General:

Angina, ischemic heart:

Diabetes:

Fatigue and athletic performance:

Lipid profiles:

Menopausal symptoms:

Notes: Natural Medicines Comprehensive Database rates American ginseng as possibly effective for type 2 diabetes and respiratory tract infections. NCCIH (2016. Asian ginseng) states "There’s currently no conclusive evidence supporting any health benefits of Asian ginseng." Siberian ginseng (Eleutherococcus senticosus) (see below) is a much different plant.


Goji (wolfberry, fruit of Lycium barbarum or L. chinense)

Uses: "many conditions including diabetes, weight loss, improving quality of life, and as a tonic" (MedlinePlus 2019. Goji).

Possible toxic effects: allergic reactions, may lower blood glucose, may lower blood sugar, interactions with some drugs

Review: Potterat 2010. Planta Med. 76(1): 7-19: “In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.”

Notes: according to MedlinePlus, there is "insufficient evidence to rate effectiveness" for any condition.


Golden root (Rhodiola rosea and other species of Rhodiola)

Uses: an “adaptogen” to reduce stress; boost immunity, increase energy, antiviral, antioxidant, anti-aging, anti-depression

Presumed active agents: salidroside, rhodionin, rhodiosin

Presumed mechanisms of action: inhibition of MAPK and NF-κB pathways by salidroside, enhanced production of IL-6, other


Goldenseal (Hydrastis canadensis)

Uses: "colds and other respiratory tract infections, allergic rhinitis (hay fever), ulcers, and digestive upsets such as diarrhea and constipation. It is also used as a mouthwash for sore gums and as an eyewash for eye inflammation, and it is applied to the skin for rashes and other skin problems" (NCCIH 2016. Goldenseal).

Presumed active agents: hydrastine, berberine

Presumed mechanisms of action: antimicrobial and antiviral effects

Possible toxic effects: nausea, vomiting, diarrhea, CNS stimulation, respiratory failure, increased blood pressure, diuretic effects. "Goldenseal has been shown to inhibit CYP2D6 [cytochrome P450 2D6] and CYP3A4 [cytochrome P450 3A4]. These two enzymes metabolize 50% of current pharmaceutical agents. It is strongly recommended to avoid taking goldenseal with most prescription and over-the-counter medications" (Furhad and Bokhari 2020. Herbal Supplements. StatPearls). Should not be taken in pregnancy and breastfeeding, or given to infants.

Review: Beba et al. 2019. Complement Ther Med. 46:81-6: Review of berberine indicated that it might reduce inflammation and be beneficial for patients with heart disease or diabetes.

Notes: "The scientific evidence does not support the use of goldenseal for any health-related purpose.

Berberine, a substance found in goldenseal, has been studied for heart failure, diarrhea, infections, and other health conditions. However, when people take goldenseal orally (by mouth), very little berberine may be absorbed by the body or enter the bloodstream, so study results on berberine may not apply to goldenseal" (NCCIH).


Guarana (Paullinia cupana)

Uses: "obesity, athletic performance, mental performance, to increase energy, as an aphrodisiac, and for many other conditions" (MedlinePlus 2019. Guarana).

Presumed active agents: caffeine, theophylline, theobromine

Possible toxic effects: possibly unsafe when taken in high doses for a long time, due to caffeine content. "At typical doses, the caffeine in guarana can cause insomnia, nervousness and restlessness, stomach irritation, nausea, vomiting, increased heart rate and blood pressure, rapid breathing, tremors, delirium, diuresis, and other side effects. Large guarana doses might cause headache, anxiety, agitation, ringing in the ears, pain when urinating, stomach cramps, and irregular heartbeats" (MedlinePlus).

Notes: Insufficient evidence of effectiveness for numerous conditions (MedlinePlus).


Gymnema (Gymnema sylvestre)

Uses: diabetes, weight loss, arthritis, anemia, osteoporosis, hypercholesterolemia, other

Presumed active agents: "The main constituent of gymnena is believed to be gymnemic acid, a mixture of at least 17 different saponins...However, a number of other chemical constituents have also been identified in G. sylvestre. The gymnemasaponins, for instance, are another major component of gymnema, of which there are at least seven different types. These constituents, as well as the polpeptide Gurmarin, the alkaloid conduritol, gymnamine, gypenoside, and the dammarane-type saponsins gymnemasides 1-5 and gymnemasin B, C, and D are all likely to be responsible for the hypoglycemic and antisaccharin effect of the plant" (Leach 2007. J Altern Complement Med. 13(9):977-83).

Presumed mechanisms of action: gymnesic acid blocks sweet taste sensation on the tongue. "Gynnemic acid compounds in Gymnema sylvestre can also attach to receptors on the intestinal walls, helping to reduce absorption of sugar molecules in the gut. This process can lower blood sugar and promote insulin secretion and release" (Wikipedia 2020. Gymnena sylvestre).

Possible toxic effects: can lower blood sugar, possible interactions with drugs

Review: Nahas and Moher 2009. Can Fam Physician. 55(6):591-6: "Preliminary evidence of any benefit is probably insufficient to support the widespread use of G sylvestre for diabetes management at this time."

Notes: "no good scientific evidence" to support various uses (MedlinePlus 2019. Gymnema).


Hawthorn (Crataegus oxyacantha)

Uses: chronic heart failure, ischemic heart disease, digestive and kidney problems, anxiety

Possible toxic effects: "Reported possible side effects of hawthorn include nausea, dizziness, vertigo, fatigue, sweating, headache, palpitations, and epistaxis. It is not recommended during pregnancy because it can cause uterine stimulation" (Furhad and Bokhari 2020. Herbal Supplements. StatPearls). Possible drug interactions, including with some heart medications.

Reviews:

Notes: "Although some older, short-term studies suggested that hawthorn may have benefits in patients with heart failure, two longer term studies completed in 2008 and 2009 - including a 2-year trial involving almost 2,700 people in 13 European countries - did not confirm these benefits. In these studies, unlike some of the older ones, patients were given hawthorn in addition to the recommended conventional treatments for heart failure" (NCCIH 2016. Hawthorn).


Hibiscus (various species of the genus Hibiscus)

Uses: "People use hibiscus for high blood pressure, high cholesterol, to increase the production of breast milk, and many other conditions" (MedlinePlus 2020. Hibiscus).

Possible toxic effects: Possibly unsafe in large amounts in pregnancy and breast feeding. May lower blood glucose. May lower blood pressure. May affect metabolism of many drugs.

Notes: Possibly effective for high blood pressure, no evidence of effectiveness for other conditions.


Hops (Humulus lupulus)

Uses: "orally for anxiety, sleep disorders such as the inability to sleep (insomnia) or disturbed sleep due to rotating or nighttime work hours (shift work disorder), restlessness, tension, excitability, attention deficit-hyperactivity disorder (ADHD), nervousness, irritability, and symptoms of menopause among other uses" (MedlinePlus 2019. Hops).

Presumed active agents: "The relaxing effect of hops may be due, in part, to the specific degradation product from alpha acids, 2-methyl-3-buten-2-ol, as demonstrated from nighttime consumption of non-alcoholic beer" (Wikipedia 2020. Hops).

Possible toxic effects: may make depression worse, estrogen-like effects, drowsiness, may affect metabolism of some drugs.


Horehound (Marrubium vulgare)

Uses: expectorant and cough suppression

Presumed active agents: "Horehound contains a number of constituents, including alkaloids, flavonoids , diterpenes (e.g., marrubiin), and trace amount of volatile oils" (Kaiser Permanent 2020. Horehound: how it works).

Presumed mechanisms of action: "The major active constituent in horehound is marrubiin, which is thought to be responsible for the expectorant (promotion of coughing up of mucus) action of the herb. In addition, marrubiin contributes to the bitter taste of horehound, an action that increases the flow of saliva and gastric juice, thereby stimulating the appetite. These actions likely explain the long-standing use of horehound as a cough suppressant and expectorant as well as a bitter digestive tonic" (Ibid.).

Possible toxic effects: "Since horehound acts as a bitter and may increase production of stomach acid, people with gastritis or peptic ulcer disease should use it cautiously. Horehound should not be used during pregnancy, as it may stimulate contractions" (Ibid.).

Notes: "was the top-selling supplement ingredient in 2017...with sales exceeding $140 million.. It's a common ingredient in 'herbal' cough and cold remedies, which likely accounts for its chart-topping success" (Gavura 2018 Nov 1. Science-Based Medicine blog).


Horny goat weed (various species of Epimedium)

Uses: "sexual performance problems, such as erectile dysfunction (ED) and low sexual desire. It is also used for weak back and knees, joint pain, arthritis, mental and physical fatigue, and memory loss along with many other conditions" (MedlinePlus 2019. Horny goat weed).

Presumed active agents: icariin and other flavonoids

Presumed mechanisms of action: inhibition of estrogen action, stimulation of osteoblasts

Possible toxic effects: long-term use of some forms "might cause dizziness, vomiting, dry mouth, thirst, and nosebleed. Taking large amounts of horny goat weed might cause spasms and severe breathing problems" (MedlinePlus). Estrogen-like effects, may slow blood clotting, may lower blood pressure, possible interactions with many drugs.

Notes: Lack of good evidence for any benefit.


Horse chestnut (Aesculus hippocastanum)

Uses: chronic venous insufficiency, hemorrhoids, swelling after surgery

Presumed active agent: escin

Presumed mechanisms of action: "The seed extract standardized to around 20 percent aescin (escin) is used for its venotonic effect, vascular protection, anti-inflammatory and free radical scavenging properties" (Wikipedia 2020. Aesculus hippocastanum).

Possible toxic effects: "The unprocessed seeds, leaves, bark, and flowers of horse chestnut contain esculin, which is poisonous and may increase the risk of bleeding. (Escin, on the other hand, is a different compound and is considered to be safe.) Properly processing horse chestnut seed extract removes esculin. The processed extract is considered generally safe when used for short periods of time. However, the extract can cause some side effects, including itching, nausea, gastrointestinal upset, muscle spasm, or headache" (NCCIH 2016. Horse chestnut).

Review: Pittler and Ernst 2012. Cochrane Database Syst Rev. CD003230. "The evidence presented suggests that HCSE [horse chestnut seed extract] is an efficacious and safe short-term treatment for CVI [chronic venous insufficiency]. However, several caveats exist and larger, definitive RCTs are required to confirm the efficacy of this treatment option."

Notes: "A 2012 systematic review of 17 studies published between 1976 and 2002 suggested that horse chestnut seed extract can improve leg pain, swelling, and itching in people with chronic venous insufficiency when taken for a short time. Results from one of these studies suggested that horse chestnut seed extract may be as effective as wearing compression stockings" (NCCIH).


Horsetail (Equisetum arvense)

Uses: "'fluid retention' (edema), urinary tract infections, loss of bladder control (urinary incontinence), wounds, and many other conditions" (MedlinePlus 2020. Horsetail).

Possible toxic effects: may contain an enzyme that breaks down thiamine, which would be of special concern to alcoholics (who tend to be thiamine deficient). May lower blood glucose and potassium.

Notes: no good evidence of effectiveness.


Ivy leaf (Hedera helix)

Uses: respiratory illnesses and infections

Presumed active agents: saponins, emetine

Presumed mechanisms of action: "Although emetine typically induces vomiting, in ivy leaf it seems to increase the secretion of mucus in the lungs. While the emetine content is very low in ivy, this could in part explain its traditional use as an expectorant (a substance that promotes the removal of mucous from the respiratory tract). Animal studies have shown the saponins found in ivy extract prevent the spasm of muscles in the bronchial area" (Kaiser Permanente 2015. Ivy leaf: how it works).

Possible toxic effects: "The 0.3 gram daily tea preparation of the herb, suggested in the German Commission E monographs, is not recommended for pediatric use because the quantities of the saponins it contains are too variable and could induce nausea and vomiting. Since ivy contains small amounts of emetine, it is not recommended during pregnancy, as this specific alkaloid may increase uterine contractions. In addition, the leaf itself can be quite irritating when handled and may cause allergic skin reactions" (Ibid.).

Notes: "Ivy has been studied as a cough product for children, and there is no convincing evidence that it has any meaningful effect" (Gavura 2018 Nov 1. Science-Based Medicine blog).


Kava kava (Piper methysticum)

Uses: relaxation, reduce anxiety, treat insomnia

Presumed active agents: kava pyrones

Presumed mechanism of action: enhanced GABA receptor activity

Possible toxic effects: potential for abuse, drowsiness, muscle weakness, skin discoloration, eye disturbances, allergic reactions, may be risky if combined with alcohol, liver problems. "...in a few individuals kava may be hepatotoxic due to overdose, prolonged treatment, comedication, and probably triggered by an unacceptable quality of the kava raw material; standardization is now required, minimizing thereby hepatotoxic risks" (Teschke 2010. Ann Hepatol. 9(3):251-65). "In particular, the kava product should be a water-based kava extract derived form peeled rhizomes and roots of a noble cultivar such as Borogu, of at least 5 years of age, and taken with a daily dose not exceeding 250 mg of kavalactones" (Teschke and Schulze 2010. JAMA. 304(19):2174-5).  

Reviews:

Notes: The European Union, UK, and Canada banned import in 2002 after cases of hepatotoxicity.


Kratom (Mitragyna speciosa)

Uses: pain relief, stimulant, mood elevation

Presumed active agents: mitragynine, 7-hydroxymitragynine

Presumed mechanisms of action: partial agonists of mu-opioid receptors, competitive antagonists of kappa- and delta-opioid receptors, additional actions on other types of brain receptors. "The products of the tree are known to have opioid-like sedating properties at high doses and amphetamine-like stimulating properties at lower doses" (Shekar et al. 2019. J Psychoactive Drugs. 51(1):28-30).

Possible toxic effects: opioid-like dependence; some deaths have been attributed to kratom use (see below). “Consumption of Kratom has been associated with hallucination, delusion, depression, myalgia, chill, nausea/vomiting, respiratory depression, hepatotoxicity, seizure, coma and death” (Chang-Chien et al. 2017. Pain Physician. 20(1):E195-8). Contamination of kratom products with salmonella and heavy metals has been reported.

Notes: "It was traditionally consumed in Southeast Asia to aid in manual labor, as its consumption is known to increase the ability to perform this labor. In the last decade or so, kratom has made its way into Europe and the United States..." (Shekar et al. 2019. Op. cit.). It is now consumed by millions in the U.S., but the FDA has been fighting use of kratom, attributing 44 deaths to its use as of 2018 and stating that it presents a risk of dependency and addiction. It is listed as a drug of concern by the Drug Enforcement Administration (DEA), and has been banned in several states and cities. “...kratom is hailed by some as a readily available pain remedy that is safer than traditional opioids, an effective addiction withdrawal aid and a pleasurable recreational tonic. But kratom also is assailed as a dangerous and unregulated drug that can be purchased on the Internet, a habit-forming substance that authorities say can result in opioid-like abuse and death...In the majority of deaths that FDA attributes to kratom, subjects ingested multiple substances with known risks, including alcohol. The presence of multiple drugs makes it difficult to determine the role any one of them played...On balance, my conclusion is that we urgently need more data and meanwhile should avoid this ‘herbal drug’” (Ernst 2018 Feb 13. Edzard Ernst blog).  In 2019 the CDC concluded that 91 deaths in a 17-month period were due to kratom. Eggleston et al. (2019. Pharmacotherapy. 39(7):775-7) concluded that “kratom is not reasonably expected to be safe and poses a public health threat.”


Lavender (various species of Lavandula)

Uses: "people use lavender as a dietary supplement for anxiety, depression, intestinal problems, and pain. People also apply it to the skin for hair loss, pain, and for improving emotional health. People may also inhale a lavender vapor to help sleep, to reduce pain, and for agitation related to dementia" (NCCIH 2016. Lavender).

Possible toxic effects: skin irritation from topical use. "Some evidence suggests that some topical applications containing lavender oil may affect sex hormone activity. Lavender oil may be poisonous if taken by mouth.

Lavender extracts may cause stomach upset, joint pain, or headache" (NCCIH).

Notes: "Many studies have investigated lavender’s effectiveness for a number of conditions, such as pain, anxiety, stress, and overall well-being, but several were small and of poor quality" (NCCIH). See article on holistic methods for use in aromatherapy. "


Lemon balm (Melissa officinalis)

Uses: improve cognitive function and reduce agitation in Alzheimer patients

Presumed active agents: monoterpenes such as citral, phenol carboxylic acids such as rosmarinic acid

Presumed mechanisms of action: antioxidant, anti-amyloidogenic, antiapoptotic effects


Licorice root (Glycyrrhiza glabra, G. uralensis)

Uses: coughs, hoarseness, ulcers, digestive problems, menopausal symptoms, bacterial and viral infections, liver disease

Presumed active agent: glycyrrhizin

Presumed mechanisms of action: anti-inflammatory and antiapoptotic effects via reduction in TNF-α and caspase-3.

Possible toxic effects: numerous potentially serious side effects due to mineralocorticoid action. High blood pressure, low potassium levels. "Some side effects are thought to be due to a chemical called glycyrrhizic acid. Licorice that has had this chemical removed (called DGL for deglycyrrhizinated licorice) may not have the same degree of side effects" (NCCIH 2016. Licorice root). Should be avoided during pregnancy.

Notes: Preliminary evidence of antiviral effects of glycyrrhizin. "There’s some evidence that topical licorice extract may improve skin rash symptoms, such as redness, swelling, and itching...Studies of licorice root extracts in people for cavities, mouth ulcers, and oral yeast infections have returned mixed results" (Ibid.).


Maca (Peruvian ginseng, Lepidium meyenii, L. peruvianum)

Uses: anemia, increased fertility, sexual dysfunction

Possible toxic effects: estrogen-like effects

Reviews:

Notes: no good evidence in support


Mangosteen (Garcinia mangostana)

Uses: "taken by mouth for weight loss and applied to the gums for serious gum disease. Some people take mangosteen for diarrhea and infections or apply mangosteen to the skin for eczema and other skin conditions" (MedlinePlus 2019. Mangosteen).

Notes: possibly effective for gum disease and weight loss, insufficient evidence for other conditions (MedlinePlus).


Maritime pine (Pycnogenol is an extract of the bark) (Pinus pinaster)

Uses: "Maritime pine bark extract is commonly used orally to treat and prevent diabetes, diabetes-related health issues, and problems of the heart and blood vessels among many other uses. Some people use skin creams that contain maritime pine bark extract as 'anti-aging' products. It is also applied to the skin to treat foot ulcers in people with diabetes, hemorrhoids, and mouth ulcers caused by chemotherapy" (MedlinePlus 2019. Maritime pine).

Presumed active agents: procyanidins, catechin, epicatechin, taxifolin

Presumed mechanisms of action: antioxidant, anti-inflammatory, antiplatelet, and vasodilatory actions

Possible toxic effects: may increase immune responses, bleeding, decrease blood glucose, worsen liver function in people with hepatitis

Reviews:

Notes: MedlinePlus discusses preliminary evidence in support of use for allergies, asthma, athletic performance, circulation problems, mental function, and retinal disease. "A variety of Pycnogenol dosage forms are available in the United States, including creams, gels, lotions, tablets, and capsules. Pycnogenol is also a component of more than 700 dietary supplements, cosmetic products, and foods and beverages worldwide" (Nuzum et al. 2011. Op. cit.).


Milk thistle (Silybum marianum). Silymarin is a crude preparation from milk thistle.

Uses: treatment of liver, kidney, spleen, and gallbladder problems; reduction of cholesterol, treatment of diabetes and cancer

Presumed active agents: silybin and other flavonolignans (isosilybin, silydianin, silychristin), flavonoids (taxifolin, quercetin)

Presumed mechanisms of action: protection of liver cells and acceleration of liver cell regeneration, antioxidant activity, modulation of cytokine metabolism, inhibition of NF-κB, stimulation of ribosomal RNA polymerase, inhibition of lipid peroxidation, protection against alcohol, inhibition of liver fibrosis, antiviral effects

Possible toxic effects: diarrhea, nausea, allergic reactions, may lower blood glucose

Reviews:

Notes: "Results from clinical trials of milk thistle for liver diseases have been mixed, and two rigorously designed studies found no benefit. The 2008 Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) study, sponsored by the National Institutes of Health (NIH), found that hepatitis C patients who used silymarin had fewer and milder symptoms of liver disease and somewhat better quality of life but no change in virus activity or liver inflammation. A 2012 clinical trial, cofunded by the National Center for Complementary and Integrative Health (NCCIH) and the National Institute of Diabetes and Digestive and Kidney Diseases, showed that two higher-than-usual doses of silymarin were no better than placebo for chronic hepatitis C in people who had not responded to standard antiviral treatment. Results from a 2013 clinical study suggest that milk thistle may enhance standard treatment in young people with a particular form of anemia (Cooley’s anemia)" (NCCIH 2016. Milk thistle). "In the USA, the popularity of MT derives from its use as a part of the naturopathic medical tradition of the Native Americans as well as of the Eclectic movement, a group of practitioners that recommended MT for varicose veins, menstrual problems, and congestion of the spleen, kidney, and liver in the first half of the 19th century. Actually, MT is among the top-selling herbal dietary supplements in the USA with retail sales amounting to 2.6 million dollars in the mainstream multioutlet channel in 2015" (Abenavoli et al. 2018. Op. cit.).


Moringa (Moringa oleifera)

Uses: general wellness, nutrition

Notes: used in Ayurvedic medicine. Evidence lacking for medical benefits.


Nigella (Nigella sativa) (black cumin, black seed)

Uses: asthma, diabetes, digestive issues, hypertension, other

Presumed active agents: "It contains fixed oils (lipid fraction), rich in unsaturated fatty acids, while its essential oils contain thymoquinone (the most important active compound) and the antioxidant carvacrol. Thymoquinone, a monoterpene molecule, (chemically known as 2-methyl-5-isopropyl-1,4-benzoquinone) is present in N. sativa seeds and its oil together with many bioactive compounds including, thymohydroquinone, dithymoquinone, p-cymene, carvacrol, 4-terpineol, t-anethol, sesquiterpene longifolene, α-pinene, thymol, flavonoids, and alkaloids. Seeds contain two different types of alkaloids, isoquinoline alkaloids (nigellicimine and nigellicimine-N-oxide), and pyrazol alkaloids or indazole ring bearing alkaloids (including nigellidine and nigellicine). Moreover, N. sativa seeds also contain alpha-hederin, a water-soluble pentacyclictriterpene, and saponin" (Mahmoodi and Mohammadizadeh 2020. Complement Ther Med. 50:102391).

Presumed mechanisms of action: "Beneficial effects of N. sativa preparations include the restoration of the antioxidant defense systems, the increase in the activity of antioxidant enzymes, the decrease of inflammatory biomarkers, the suppression of the production pro-inflammatory mediators, improvement of endothelial dysfunction, and hepatic, kidney, heart and immune system functions" (Ibid.).

Reviews:

Notes: used in several types of traditional medicine (Ayurveda, Unani, Siddha, Islamic medicine). Novella (2020 Jan 22. Black cumin - be skeptical. Science-Based Medicine blog) wrote: "black cumin is alleged to treat or cure an implausibly wide range of unrelated conditions. It’s almost as if it works for everything, which is a very good reason to suspect that it more likely works for nothing. Many of the conditions have completely different mechanisms – why would one product treat asthma and diabetes, cancer and liver disease? Further, many of the conditions listed are contradictory. It does not make sense that one substance would simultaneously be antimicrobial and anti-inflammatory...The clinical research is mostly preliminary, and again focusing on dozens of unrelated claims. Every single study I found was favorable, but was also not convincing due to methodological limitations...For now, there is no evidence to support black cumin as an herbal product for any indication, and there are good reasons to be skeptical."


Noni (Morinda citrifolia) - see article on dietary supplements


Olive (Olea europaea)

Uses: "Olive oil is used to prevent heart attack and stroke (cardiovascular disease), breast cancer, colorectal cancer, ovarian cancer, rheumatoid arthritis, and migraine headache. Some people use olive oil to treat constipation, high cholesterol, high blood pressure, blood vessel problems associated with diabetes, and pain associated ear infections, arthritis, and gallbladder disease. Olive oil is also used to treat jaundice, intestinal gas, and meteorism (swelling of the abdomen due to gas). It is also used to destroy the bacteria that causes some ulcers, helicobacter pylori. Some people also use olive oil to boost bacteria in the gut and as a 'cleanser' or 'purifier.' Olive oil is applied to the skin (used topically) for earwax, ringing ears (tinnitus), pain in the ears, lice, wounds, minor burns, psoriasis, stretch marks due to pregnancy, eczema, jock itch, ringworm, a skin disease caused tinea versicolor, and for protecting the skin from ultraviolet (UV) damage after sun exposure. In the mouth it is used to reduce gum disease" (MedlinePlus 2019. Olive).

Possible toxic effects: may lower blood glucose. Interactions with some drugs.

Notes: benefits of olive oil in the diet are considered in the article on dietary supplements.


Passionflower (Passiflora incarnata)

Uses: anxiety, as a sedative

Presumed active agent: chrysin

Presumed mechanism of action: partial agonist to benzodiazepine receptors

Possible toxic effects: "P incarnata has been listed as a safe herbal sedative by the US Food and Drug Administration and most drug monographs," though some adverse effects have been reported. "It is generally advised not to take P incarnata along with central nervous system stimulants or depressants...caution is suggested in recommending P incarnata to patients with cardiac abnormalities" (Modabbernia and Akhondzadeh 2013. Psychiatr Clin North Am. 36(1):85-91).

Reviews:


Pau d'arco (Handroanthus impetiginosus)

Uses: "infections, cancer, diabetes, stomach ulcers, and many others" (MedlinePlus 2018. Pau d'arco).

Presumed active agents: lapachol and beta-lapachone

Presumed mechanisms of action: “ In lab tests, these chemicals killed some bacteria, fungi, viruses, and parasites. They also have anti-inflammatory properties, and may be effective against diseases such as osteoarthritis” (Penn State Hershey A.D.A.M. 2017. Pau d’arco).

Possible toxic effects: "Pau d'arco is POSSIBLY UNSAFE when taken by mouth. In high doses, pau d'arco can cause severe nausea, vomiting, diarrhea, dizziness, and internal bleeding. The safety of pau d'arco in typical doses is not known" (MedlinePlus). Likely unsafe in larger doses during pregnancy and lactation. Might slow blood clotting.

Notes: Pau d'arco is a tree whose bark and wood are used for making medicine. "Commercial products containing pau d'arco are available in capsule, tablet, extract, powder, and tea forms. But sometimes it's hard to know what is in pau d'arco products. Some studies have shown that some pau d'arco products sold in Canada, Brazil, and Portugal do not contain the active ingredients in the correct amounts" (MedlinePlus). No good evidence of effectiveness. "Early research shows that pau d'arco might prevent cancer cells from growing. It might also slow tumor growth by preventing the tumor from growing the necessary blood vessels. However, the doses needed to cause anticancer effects seem to cause serious side effects in humans" (Medline Plus).


Pennyroyal (Mentha pulegium) is considered likely unsafe (see section on hazards).


Peppermint oil (Menta piperita)

Uses: irritable bowel syndrome (IBS) and dyspepsia, colds, headache

Possible toxic effects: allergic reactions, heartburn. Rashes or irritation if applied to skin. "Peppermint oil should not be applied to the face or chest of infants or young children because serious side effects may occur if they inhale the menthol in the oil" (NCCIH 2016. Peppermint oil).

Reviews:

Notes: "Peppermint oil has been studied most extensively for IBS. Results from several studies indicate that peppermint oil in enteric-coated capsules may improve IBS symptoms. A few studies have indicated that peppermint oil, in combination with caraway oil, may help relieve indigestion, but this evidence is preliminary and the product that was tested is not available in the United States. Peppermint oil has been used topically for tension headaches and a limited amount of evidence suggests that it might be helpful for this purpose. There’s not enough evidence to allow any conclusions to be reached about whether peppermint oil is helpful for nausea, the common cold, or other conditions. There’s not enough evidence to show whether peppermint leaf is helpful for any condition" (NCCIH).


Psyllium (black psyllium, blond psyllium. Various Plantago species)

Uses: constipation, diarrhea, dysentery, irritable bowel syndrome, cancer, high cholesterol, prevention of heart disease

Presumed active agent: soluble fiber

Presumed mechanisms of action: absorbs excess water in the intestinal tract. This "adds bulk to the stool which might help with constipation, diarrhea, and irritable bowel syndrome. It also controls how quickly sugars are absorbed from the gut, which might help control blood sugar levels in people with diabetes" (MedlinePlus 2020. Black psyllium).

Possible toxic effects: bloating, gas. Unsafe if not taken with enough water (risk of choking). Allergic reactions. Can interfere with absorption of some drugs, as well as glucose and nutrients.

Reviews:

Notes: "Black psyllium is safe and effective for short-term, over-the-counter use for treating constipation...can help reduce the risk of coronary heart disease," while insufficient evidence for other uses (MedlinePlus 2020. Black psyllium). Similar comments apply to blond psyllium.


Pycnogenol - see maritime pine


Red clover (Trifolium pratense)

Uses: "Historically, red clover was used for a variety of conditions including asthma, whooping cough, cancer, and gout. Today, isoflavone extracts from red clover are most often used as dietary supplements for menopausal symptoms, high cholesterol, or osteoporosis" (NCCIH 2016. Red clover).

Presumed active agents: isoflavones (formononetin, biochanin A, daidzein, genistein)

Presumed mechanisms of action: agonists/antagonists of estrogen receptors

Possible toxic effects: Possible estrogen-like effects.

Reviews:

Notes: "There have been several studies of red clover in people, but their results haven’t provided clear evidence of any beneficial effects" (NCCIH).


Rhodiola - see golden root


Roman chamomile (Chamaemelum nobile) (see also chamomile above)

Uses: "Some people take Roman chamomile by mouth for various digestive disorders including upset stomach (indigestion), nausea, vomiting, loss of appetite, and intestinal gas (flatulence). It is also commonly applied to the skin for pain and swelling (inflammation) and included as a germ-killer in ointments, creams, and gels used to treat cracked nipples, sore gums, and irritation of the skin. Some people put Roman chamomile in a steam bath and inhale it for sinus inflammation, hay fever, and sore throat" (MedlinePlus 2019. Roman chamomile).

Presumed active agents: "The essential oil of Roman chamomile contains less chamazulene [than German chamomile] and is mainly constituted from esters of angelic acid and tiglic acid. It also contains farnesene and a-pinene. Roman chamomile contains up to 0.6% of sesquiterpene lactones of the germacranolide type, mainly nobilin and 3-epinobilin" (Srivastava et al. 2010. Mol Med Rep. 3(6):895-901).

Possible toxic effects: Likely unsafe in medicinal amounts during pregnancy (may cause miscarriage); allergic reactions

Notes: insufficient evidence of effectiveness for any use.


Rose hip (various species of Rosa)

Uses: "Rose hip is commonly used by mouth for osteoarthritis. It is also used by mouth to treat stomach problems, infections, and obesity and applied to the skin for stretch marks" (MedlinePlus 2019. Rose hip).

Presumed active agents: vitamin C (ascorbic acid), beta carotene, lutein, zeaxanthin, lycopene

Possible toxic effects: Increased vitamin C from rose hips may cause problems in some conditions. "Rose hip contains rugosin E. Rugosin E might cause blood clots."

Review: Christensen et al. 2008. Osteoarthritis Cartilage. 16(9):965-72: “Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.”

Notes: "Rose hip is the round portion of the rose flower just below the petals. Rose hip contains the seeds of the rose plant. Dried rose hip and the seeds are used together to make medicine. Fresh rose hip contains a lot of vitamin C, so some people take it as a source of vitamin C to prevent and treat colds, flu, and vitamin C deficiencies. However, much of the vitamin C in rose hip is destroyed during drying and processing and declines rapidly during storage. Because of this, many rose hip-derived 'natural' vitamin C products have actually been fortified with lab-made vitamin C, but their labels may not always say so" (MedlinePlus). Possibly effective for osteoarthritis, insufficient evidence for other uses.


Sage (Salvia officinalis, S. lavandulaefolia)

Uses: "digestive problems, sore mouth or throat, memory loss, and depression" (NCCIH 2016. Sage).

Presumed mechanisms of action: “The pharmacological activities of sage that are relevant to AD [Alzheimer’s disease] include antioxidant activity, anti-inflammatory effects and weak AChE [acetylcholinesterase] inhibition” (Izzo and Capasso 2007. Trends Pharmacol Sci. 28(2):47-8).

Possible toxic effects: "some species of sage contain thujone, which can affect the nervous system. Extended use or taking large amounts of sage leaf or oil may result in restlessness, vomiting, vertigo, rapid heart rate, tremors, seizures, and kidney damage. Twelve drops or more of the essential oil is considered a toxic dose" (NCCIH).

Reviews:

Notes: "We don’t know much about the health effects of sage because little research has been done on it" (NCCIH). “There is encouraging clinical evidence that sage might alleviate the symptoms of AD” (Izzo and Capasso 2007. Op. cit.).


St. John's wort (Hypericum perforatum)

Uses: treatment of depression, viral infections, emotional and behavioral complications in children, obsessive-compulsive disorder, premenstrual syndrome, and psoriasis

Presumed active agents: hypericin, pseudohypericin, hyperforin, phenolic acids. “Though it was initially thought that the hypericin component is responsible for St John’s wort’s antidepressant activity, the general consensus now is that the hyperforin component is key” (Ng et al. 2017. J Affect Disord. 210:211-21). However, products are usually standardized to hypericin content, and the amount of hyperforin may not be listed.

Presumed mechanisms of action: inhibition of reuptake of serotonin, dopamine, norepinephrine; inhibition of monoamine oxidase, resulting in an increase in norepinephrine; inhibition of gamma-aminobutyric acid (GABA) binding to its receptors.

Possible toxic effects: dangerous drug interactions possible: appears to increase metabolism of numerous commonly used drugs. Gavura (2018 Apr 5. Science-Based Medicine blog) noted that “SJW is one of the worst offenders, seemingly causing drug interactions with almost every drug product on the market...The safest approach is to assume that SJW shouldn’t be taken concurrently with any other medication, without verifying a lack of problem with a pharmacist.” Other possible effects include photodermatitis, stomach upset, allergy, dizziness, dry mouth, restlessness, fatigue; also, “elevated thyroid stimulating hormones, hypertensive crisis, and induction of mania” (Apaydin et al. 2016. Syst Rev. 5(1):148). It has been suggested that in bright sunlight it could lead to cataracts. High blood pressure when taken with foods containing tyramine.

Reviews:

Notes: “The data on St. John’s Wort is of mixed quality, with the research methods often poorly described. Studies are generally of a short duration and usually funded by manufacturers (which is also the case for many pharmaceutical antidepressants)...” (Gavura 2018. Op. cit.). The Cochrane review noted that “findings were more favourable to St. John’s wort extracts in studies from German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St. John’s wort extracts seemed less effective. This differences could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results.” An analysis of 47 commercial products found a significant degree of adulteration with other species and with food dyes (Booker et al. 2018. Phytomedicine. 40:158-64).


Saw palmetto (Serenoa repens)

Uses: treatment of benign prostate hyperplasia and urinary problems, pelvic pain, decreased sex drive, migraine, hair loss, other

Presumed active agents: β-sitosterol and other steroid-like compounds

Presumed mechanisms of action: possibly antiandrogenic effects via inhibition of 5-α reductase and of binding of dihydrotestosterone to receptors, anti-inflammatory effects via inhibition of cyclooxygenase and lipoxygenase

Possible toxic effects: stomach upset, headache, diarrhea. Does not appear to interfere with PSA tests for prostate cancer. Increased risk of bleeding if taking warfarin. “Saw palmetto has so far been implicated in hepatitis, cholecystitis, bleeding diathesis, conduction defects, and erectile dysfunction” (Jibrin et al. 2006. South Med J. 99(6):611-2).

Review: Tacklind et al. 2012. Cochrane Database Syst Rev. CD001423.: “Serenoa repens, at double and triple doses, did not improve urinary flow measures or prostate size in men with lower urinary tract symptoms consistent with BPH [benign prostatic hyperplasia].”

Notes: Placebo effects of 50% seen in some trials, which can account for anecdotal reports of success. A strong odor makes it difficult to conduct blinded studies. "The scientific evidence does not support using saw palmetto for any health condition. High-quality scientific studies have shown that saw palmetto is no more effective than a placebo (an inactive substance) in relieving urinary tract symptoms caused by prostate enlargement. These studies include a 2011 NIH-funded study that tested saw palmetto in amounts up to three times the usual dose" (NCCIH 2016. Saw palmetto).


Senna (Cassia acutifolia or Senna alexandrina (Alexandrian senna), C. angustifolia (Indian or Tinnevelly senna))

Uses: constipation, irritable bowel syndrome, anal or rectal surgery, hemorrhoids, weight loss

Presumed active agents: sennosides

Presumed mechanisms of action: “Sennosides irritate the lining of the bowel, which causes a laxative effect“ (WebMD 2020. Senna).

Possible toxic effects: "Senna is POSSIBLY UNSAFE when taken by mouth long-term or in high doses. Don't use senna for more than two weeks. Longer use can cause the bowels to stop functioning normally and might cause dependence on laxatives. Long-term use can also change the amount or balance of some chemicals in the blood (electrolytes) that can cause heart function disorders, muscle weakness, liver damage, and other harmful effects" (MedlinePlus 2019. Senna). Can affect absorption of estrogens. Can increase risk of bleeding if taking warfarin.

Reviews:

Notes: "Senna is an FDA-approved over-the-counter (OTC) laxative" (MedlinePlus). Likely effective for constipation, insufficient evidence for other uses.


Siberian ginseng (Eleutherococcus senticosus)

Uses: claims are similar to those for Panax ginseng. Used as an "adaptogen," to boost the immune system, prevent colds, and increase appetite. It is also used for "conditions of the heart and blood vessels such as high blood pressure, low blood pressure, hardening of the arteries (atherosclerosis), and rheumatic heart disease. It is also used for kidney disease, Alzheimer's disease, attention deficit-hyperactivity disorder (ADHD), chronic fatigue syndrome, diabetes, high cholesterol, improving loss of sensation in extremities (peripheral neuropathy), fibromyalgia, rheumatoid arthritis, reducing the effects of a hangover, flu, colds, chronic bronchitis, and tuberculosis...treating the side effects of cancer chemotherapy...to improve athletic performance and the ability to do work...to treat sleep problems (insomnia) and the symptoms of infections caused by herpes simplex type 2" (MedlinePlus 2019. Eleuthero).

Presumed active agents: eleutherosides, complex polysaccharides

Possible toxic effects: slowing of blood clotting, pounding heart, irregular heartbeat, high blood pressure, effects on blood glucose, estrogen-like effects. May affect drug metabolism by liver and have other drug interactions.

Review: Panossian et al. 2009. Curr Clin Pharmacol. 4(3):198-219: "Good scientific evidence has been documented in trails [sic] in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness."

Notes: MedlinePlus rates as possibly effective for bipolar disorder, relieving symptoms of common cold (when taken with another herb, andrographis), diabetes, herpes simplex 2; insufficient evidence for other uses.


Silymarin - see milk thistle


Slippery elm (Ulmus fulva, U. rubra)

Uses: "People take slippery elm by mouth for coughs, sore throat, colic, diarrhea, constipation, hemorrhoids, irritable bowel syndrome (IBS), bladder and urinary tract infections and inflammation, syphilis, herpes, and for expelling tapeworms. It is also used for protecting against stomach and duodenal ulcers, for colitis, diverticulitis, gastrointestinal inflammation, and too much stomach acid. Slippery elm is also taken by mouth to cause an abortion and for cancer. Slippery elm is applied to the skin for wounds, burns, gout, rheumatism, cold sores, boils, abscesses, ulcers, toothaches, sore throat, and as a lubricant to ease labor" (MedlinePlus 2017. Slippery elm).

Presumed mechanisms of action: “The mucilage of slippery elm, found in the inner bark, gives it the soothing effect for which it is known. In people with heartburn , the mucilage appears to act as a barrier against the damaging effects of acid on the esophagus. It may also have an anti-inflammatory effect locally in the stomach and intestines” (Kaiser Permanente 2020. Slippery elm).

Possible toxic effects: When applied to skin, possible allergic reactions or skin irritation. "Slippery elm contains a type of soft fiber called mucilage. Mucilage can decrease how much medicine the body absorbs. Taking slippery elm at the same time you take medications by mouth can decrease the effectiveness of your medication. To prevent this interaction, take slippery elm at least one hour after medications you take by mouth" (MedlinePlus).

Notes: "Slippery elm seems to soothe sore throats. Commercial lozenges containing slippery elm are preferred to the native herb when used for this condition. The lozenges prolong the pain-killing effect" (MedlinePlus). Insufficient evidence in support of other claimed benefits.


Stevia (Stevia rebaudiana)

Uses: "It is probably best known as a source of natural sweeteners. Some people take stevia by mouth for medical purposes such as lowering blood pressure, treating diabetes, heartburn, high uric acid levels in the blood, for weight loss, to stimulate the heart rate, and for water retention" (MedlinePlus 2019. Stevia).

Presumed active agents: steviol glycosides (stevioside and rebaudioside)

Presumed mechanisms of action: “According to basic research, steviol glycosides and steviol interact with a protein channel called TRPM5, potentiating the signal from the sweet or bitter receptors, amplifying the taste of other sweet, bitter and umami tastants. The synergetic effect of the glycosides on the sweet receptor and TRPM5 explains the sweetness sensation” (Wikipedia 2020. Stevia).

Possible toxic effects: allergies if sensitive to ragweed, nausea or bloating, dizziness, muscle pain, numbness. Controversial whether it lowers blood sugar. May lower blood pressure. May lower lithium levels.

Notes: "In the US, stevia leaves and extract are not approved for use as a sweetener, but they can be used as a ‘dietary supplement’ or in skin care products. In December 2008, the U.S. Food and Drug Administration (FDA) granted Generally Recognized as Safe (GRAS) status to rebaudioside A, one of the chemicals in stevia, to be used as a food additive sweetener" (MedlinePlus). Insufficient evidence of effectiveness for other uses.


Stinging nettle (Urtica dioica)

Uses: various conditions, including as a diuretic and for benign prostate hypertrophy.

Review: Chrubasik et al. 2007. Phytomedicine. 14(7-8):568-79: "The clinical evidence of effectiveness for nettle root in the treatment of BPH [benign prostatic hyperplasia] is based on many open studies. A small number of randomised controlled studies indicate that a proprietary methanolic extract is effective in improving BPH complaints. However, the significance and magnitude of the effect remains to be established in further confirmatory studies before nettle root treatment may be accepted in the guidelines for BPH treatment."


Tea (green, black) (Camellia sinensis and other species of Camellia and Thea)

Uses: prevention of cancer, heart disease, and Parkinson’s; treatment of arthritis, headache, and both high and low blood pressure; improved alertness and other mental functions

Presumed active agents:  "Although constituents and proportions of various tea preparations vary, the primary bioactive compounds are polyphenols, most of which are members of the flavanol (flavan-3-ol) subclass of flavonoids known as catechins. Four major catechins are present in tea: epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). The relative concentration of these catechins is substantially greater in green tea than in black tea because during the processing of black tea, which involves fermentation, the catechins are oxidized and converted into other compounds, known as theaflavins and thearubigans [also thearubigins, thearubigens]..." (Melnick 2006. J Pediatr Hematol Oncol. 28(4):221-85). Other constituents include caffeine, theobromine, and L-theanine. "For therapeutic purposes, green tea is often administered as an encapsulated extract (green tea extract, GTE) and standardized to EGCG" (Fritz et al. 2013. Integr Cancer Ther. 12(1):7-24).

Presumed mechanisms of action: Flavonoids as antioxidants; the catechin EGCG is thought to inhibit tumor growth and cartilage breakdown. Tea may also enhance insulin action. L-Theanine may stimulate the immune system. "We report that although the catechins are chemical antioxidants which can quench free radical species and chelate transition metals, there is evidence that some of the effects of these compounds may be related to induction of oxidative stress. Such pro-oxidant effects appear to be responsible for the induction of apoptosis in tumor cells. These pro-oxidant effects may also induce endogenous antioxidant systems in normal tissues that offer protection against carcinogenic insult" (Lambert and Elias 2010. Arch Biochem Biophys. 501(1):65-72). "Caffeine inhibits phosphodiesterase, increasing cyclic adenosine monophosphate and enhancing the activity of certain excitatory neurotransmitters. However, caffeine’s primary neurobiological effect may be through its activity as an antagonist at the adenosine receptor, impairing the presynaptic inhibitory function of adenosine, thereby increasing excitatory neurotransmitter release. Tea catechins act by inhibiting catechol-o-methyl-transferase, which is an enzyme that degrades norepinephrine. Thus, the actions of catechins and caffeine in green tea act in concert to enhance the stimulatory effects of norepinephrine" (Hollander and Mechanick 2008. J Am Diet Assoc. 108(3):495-509). EGCG is alleged to be "thermogenic," causing cells to burn extra calories.

Possible toxic effects: more than five cups per day possibly unsafe. Headache, nervousness, sleep problems, and many other possible effects associated with caffeine. Hazards of use in combination with many drugs and herbs. “When using green tea derivatives such as extracts, safety concerns can rise, depending on the type of preparation and the dose of active components. In some extracts, EGCG content can reach up to 95%: Such a product cannot be still named ‘green tea,’ it is a pure substance, so we cannot rely on its long-lasting use as a safety warranty” (Mazzanti et al. 2015. Arch Toxicol. 89(8):1175-91). Health Canada has required warning labels on green tea extract due to risk of liver injury. Dekant et al. (2017. Toxicol Lett. 277:104-8) wrote, "a tolerable upper intake level of 300 mg EGCG/person/day is proposed for food supplements; this gives a twofold safety margin to clinical studies that did not report liver effects." A review by the United States Pharmacopeia (Oketch-Rabah et al. 2020. Toxicol Rep. 7:386-402) found "a clear occurrence of severe hepatotoxicity" from green tea extracts "albeit with very low frequency...The setting of a dose below which toxicity will not occur was deemed impractical due to a possible role of genetic factors and the idiosyncratic nature of hepatotoxicity in humans."

Reviews:

Both green and black tea:

Green tea:

Notes: FDA has concluded that it is highly unlikely that green tea reduces the risk of breast and prostate cancer. According to MedlinePlus (2019. Black tea), effectiveness ratings for black tea are: likely effective - mental alertness; possibly effective - low blood pressure, heart attack risk, osteoporosis, ovarian cancer risk, Parkinson's risk; possibly ineffective for prevention of diabetes and various other types of cancer. According to NCCIH (2016. Green tea), "Very few long-term studies have investigated the effects of tea on heart disease risk. However, the limited evidence currently available suggests that both green and black tea might have beneficial effects on some heart disease risk factors, including blood pressure and cholesterol. Green tea extracts haven’t been shown to produce a meaningful weight loss in overweight or obese adults. They also haven’t been shown to help people maintain a weight loss." In 2006 the FDA rejected a proposed health claim for prevention of cardiovascular disease by green tea.


Tea tree oil (melaleuca oil; Melaleuca alternifolia)

Uses: "used externally for various conditions such as acne, athlete’s foot, lice, nail fungus, cuts, and insect bites" (NCCIH 2016. Tea tree oil).

Possible toxic effects: "Tea tree oil should not be swallowed. Taking it orally can cause serious symptoms such as confusion and ataxia (loss of muscle coordination). Most people can use topical products containing tea tree oil without problems, but some people may develop contact dermatitis (an allergic skin rash) or skin irritation on the parts of the body where the product was used" (NCCIH).

Notes: "Only a small amount of research has been done on the topical use of tea tree oil for health conditions in people...A limited amount of research indicates that tea tree oil might be helpful for acne, nail fungus, and athlete’s foot."


Thunder God Vine (Tripterygium wilfodii Hook F)

Uses: rheumatoid arthritis and other immune and inflammatory diseases

Presumed active agents: "Celastrol...also called tripterine, and triptolide, a diterpenoid triepoxide, are the two most widely studied and promising compounds isolated from Thunder God Vine" (Salminen et al. 2010. Biochem Biophys Res Commun. 394(3):439-42).

Presumed mechanisms of action: “Triptolide has pharmacological activities including anti-inflammatory, immune modulation, antiproliferative, and proapoptotic activity, but its clinical use is limited by severe toxicity. The biological target of triptolide is believed to be the XPB subunit of the TFIIH protein complex (involved in DNA repair and transcription initiation)” (Wikipedia 2020. Tripterygium wilfordii).

Possible toxic effects: "decreased bone mineral content (with long-term use), infertility, menstrual cycle changes, rashes, diarrhea, headache, and hair loss. Because some of these side effects are serious, the risks of using thunder god vine may be greater than its benefits. Thunder god vine can be extremely poisonous if the extract is not prepared properly" (NCCIH 2016. Thunder god vine).

Review: Bao et al. 2011. Rheumatol Int. 31(9):1123-9: " Except numerous uncontrolled clinical trials, there are some prospective, double-blind, randomized, and placebo/sulfasalazine-controlled trials, also demonstrating greater improvement in RA [rheumatoid arthritis] disease activity by TwHF extract than placebo/sulfasalazine. Radiographic progression in RA may also be retarded by TwHF. Therefore, the immunosuppressive, cartilage protective, and anti-inflammatory effects of TwHF extracts are well demonstrated, and TwHF extract is an alternative disease modifying anti-rheumatic drug (DMARD) for the patients with RA refractory to conventional therapy."

Notes: Some evidence of benefit for rheumatoid arthritis. "There is not enough evidence to show whether thunder god vine is helpful for any health conditions other than rheumatoid arthritis or whether its topical use in rheumatoid arthritis has any benefits" (NCCIH).


Turmeric (Curcuma longa, C. aromatica, C. domestica) and curcumin

Uses: "Historically, turmeric has been used in Ayurvedic medicine, primarily in South Asia, for many conditions, including breathing problems, rheumatism, serious pain, and fatigue. Today, turmeric is used as a dietary supplement for inflammation; arthritis; stomach, skin, liver, and gallbladder problems; cancer; and other conditions" (NCCIH 2016. Turmeric).

Presumed active agents: curcumin (diferuloylmethane), demethoxycurcumin, bis-demethoxycurcumin

Presumed mechanisms of action: antioxidant and antitumor effects. "Curcumin inhibits a number of cellular processes involved in carcinogenesis and tumor growth. It regulates an array of cellular processes such as inhibition of lipid peroxidation, nitric oxide synthetase activity, epidermal growth factor receptor kinase C activity, nuclear factor (NF)-κB activity, protein kinase C activity, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and production of reactive oxygen species. Inhibition of the expression of several proto-oncogenes and cell proliferation genes in tumor cells (c-myc, c-fos, c-jun) has also been reported" (Melnick 2006. J Pediatr Hematol Oncol. 28(4):221-30).

Possible toxic effects: "High doses or long-term use of turmeric may cause gastrointestinal problems" (NCCIH).

Reviews:

Notes: Fifth-most popular herb in 2017, with sales of $32 million. "Claims that curcuminoids found in turmeric help to reduce inflammation aren’t supported by strong studies. Preliminary studies found that curcuminoids may:

Ernst (2016 Jun 22. Edzard Ernst blog) wrote, "What emerges from a critical reading of the evidence is that turmeric has potential in several different areas. Generally speaking, clinical trials are still thin on the ground, not of sufficient rigor and therefore not conclusive."


Uva ursi (Arctostaphylos)

Uses: "has been used to treat dysuria, cystitis, urethritis, and kidney and bladder stones. It has also been recommended for inducing diuresis and to treat constipation...More recently, uva ursi has been included in multiingredient dietary supplements meant for a variety of conditions such as to induce weight loss, promote wellness, prevent the effects of aging and to increase energy and stamina" (Anon. 2020. Uva Ursi. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury).

Presumed active agents: hydroquinones, particularly arbutin and methyl arbutin

Presumed mechanisms of action: antiinflammatory and antiseptic actions

Possible toxic effects: "Side effects are not common but, in high doses, may include nausea, vomiting, tinnitus, shortness of breath and allergic reactions. Rare but potentially severe reactions to high doses of uva ursi may include convulsions, delirium and cardiovascular collapse...There have been no convincing published instances of clinically apparent liver injury attributed to uva ursi" (Ibid.).

Notes: "there is no convincing medical evidence that it is effective in treating urinary tract infections or urinary symptoms" (Ibid.).


Valerian (Valeriana officinalis)

Uses: promote sleep; treat depression, anxiety, convulsions, ADHD, and menopausal symptoms.

Presumed active agents: valepotriates (valtrate, isovaltrate, dihydrovaltrate), others

Presumed mechanism of action: may increase GABA levels at synapses

Possible toxic effects: increased morning drowsiness, lack of coordination, fatigue, headache, dizziness, itching, digestive disturbances; possible depression with long-term use

Reviews:

Notes: May need two weeks of use to become effective. "The evidence on whether valerian is helpful for sleep problems is inconsistent. There’s not enough evidence to allow any conclusions about whether valerian can relieve anxiety, depression, or menopausal symptoms" (NCCIH 2016. Valerian).


Willow bark (various species of Salix)

Uses: "Willow bark acts a lot like aspirin, so it is used for pain, including headache, muscle or joint pain, menstrual cramps, rheumatoid arthritis (RA), osteoarthritis, gout, and a disease of the spine called ankylosing spondylitis...Willow bark is also used for the common cold, flu, and weight loss" (MedlinePlus 2018. Willow bark).

Presumed active agent: salicin

Presumed mechanisms of action: “Salicin, upon oral administration, is metabolized (which involves glycon hydrolysis and oxidation of benzyl carbon) in the gastrointestinal tract and bloodstream into the pharmacological active form, salicylic acid. These compounds have been identified to exert a modulating role in inflammatory processes (inhibition of the activation of NF-κB and downregulating COX-2 [cyclooxygenase-2] expression)” (Bartnik and Facey 2017. Pharmacognosy).

Possible toxic effects: "It may cause headaches, stomach upset, and digestive system upset. It can also cause itching, rash, and allergic reactions, particularly in people allergic to aspirin... Not enough is known about the safety of using willow bark during pregnancy. It's best to avoid using it. Using willow bark while breast-feeding is POSSIBLY UNSAFE. Willow bark contains chemicals that can enter breast milk and have harmful effects on the nursing infant...POSSIBLY UNSAFE in children when taken by mouth for viral infections such as colds and flu. There is some concern that, like aspirin, it might increase the risk of developing Reye's syndrome...Willow bark might increase the risk of bleeding in people with bleeding disorders...Willow bark might reduce blood flow through the kidneys, which might lead to kidney failure in certain people" (MedlinePlus). Interactions with some medications.

Review: Gagnier et al. 2016. Spine (Phila Pa 1976). 41(2):116-133 (Cochrane review of low back pain): "Although Harpagophytum procumbens (devil's claw), Salix alba (white willow bark), Symphytum officinale L. (comfrey), Solidago chilensis (Brazilian arnica), and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best."

Notes: Possibly effective for low back pain, insufficient evidence for other uses.


Yerba mate (Ilex paraguariensis)

Uses: "to relieve mental and physical tiredness (fatigue), as well as chronic fatigue syndrome (CFS). It is also taken by mouth for heart-related complaints including heart failure, irregular heartbeat, and low blood pressure....to improve mood and depression; for diabetes; high cholesterol; weak bones (osteoporosis); to relieve headache and joint pains; to treat urinary tract infections (UTIs), and bladder and kidney stones; for weight loss; and as a laxative" (MedlinePlus 2019. Yerba mate).

Presumed active agents: caffeine, theophylline, theobromine, polyphenols

Presumed mechanisms of action: “Yerba mate has been claimed to have various effects on human health, most of which have been attributed to the high quantity of polyphenols found in the beverage. Research has found that yerba mate may improve allergy symptoms and reduce the risk of diabetes mellitus and high blood sugar in mice. Mate also contains compounds that may act as an appetite suppressant and possible weight loss tool, increases mental energy and focus, improves mood, and promotes deeper sleep; however, sleep may be negatively affected in people who are sensitive to caffeine....Yerba mate contains polyphenols such as flavonoids and phenolic acids, which work by inhibiting enzymes like pancreatic lipase and lipoprotein lipase, which in turn play a role in fat metabolism. Yerba mate has been shown to increase satiety by slowing gastric emptying. Effects on weight loss may be due to reduced absorption of dietary fats and/or altered cholesterol metabolism” (Wikipedia 2020. Yerba mate).

Possible toxic effects: "Yerba mate contains caffeine, which in some people can cause side effects such as inability to sleep (insomnia), nervousness and restlessness, upset stomach, nausea and vomiting, increased heart rate and breathing, and other side effects. Yerba mate is POSSIBLY UNSAFE when taken in large amounts or for long periods of time. Consuming large amounts of yerba mate (more than 12 cups daily) might cause headache, anxiety, agitation, ringing in the ears, and irregular heartbeats. Drinking large amounts of yerba mate (1-2 liters daily) also increases the risk of esophageal cancer, kidney cancer, stomach cancer, bladder cancer, cervical cancer, prostate cancer, lung cancer, and possibly laryngeal or mouth cancer. This risk is especially high for people who smoke or drink alcohol" (MedlinePlus). Possibly unsafe during pregnancy and breast feeding due to caffeine and possible cancer-causing chemicals. Caffeine may produce unfavorable effects when used with numerous drugs.

Review: Bracesco et al. 2011. J Ethnopharmacol. 136(3):378-84: "Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders."

Notes: Insufficient evidence of effectiveness for any use.


Yohimbe (Pausinystalia johimbe)

Uses: "impotence, athletic performance, weight loss, chest pain, high blood pressure, diabetic neuropathy, and more" (NCCIH 2016. Yohimbe).

Presumed active agents: yohimbine

Presumed mechanisms of action: blocking of α2-adrenergic receptor, leading to stimulation of erection through several pathways

Possible toxic effects: "Yohimbe has been associated with heart attacks and seizures. Yohimbe caused stomach problems, tachycardia (a rapid heartbeat), anxiety, and high blood pressure..." (NCCIH). See also discussion of dangerous herbs and ephedra above.

Review: Tam et al. 2001. Pharmacol Ther. 91(3):215-43: "Overall, the benefit risk profile of YOH [yohimbine] would indicate that it has potential, more probably as part of a combination strategy, e.g., with a drug that enhances the nitric oxide pathway, in the treatment of ED [erectile dysfunction]."

Notes: "There is very little research in people on the effects of yohimbe as a dietary supplement. But studies have documented the risks of taking it...Yohimbine hydrochloride, a standardized form of yohimbine, is available in the United States as a prescription drug for erectile dysfunction. This is a different product than dietary supplements made from the bark of the tree...Most yohimbe products don’t say how much yohimbine they contain. The amount may vary a lot among products, according to a recent analysis of 49 brands of supplements labeled as containing yohimbe or yohimbine for sale in the United States. Some of the yohimbine was either synthetic or from highly processed plant extract" (NCCIH).


REFERENCES

Herbs - overview

NIH Office of Dietary Supplements. 2020. Botanical dietary supplements: Background information

American Botanical Council.  Herbal Library

National Library of Medicine. MedlinePlus. Herbs and supplements

Furhad S, Bokhari AA. 2020. Herbal supplements. StatPearls

O’Hara MA, Kiefer D, Farrell K, Kemper K 1998. A review of 12 commonly used medicinal herbs. Arch Fam Med. 7(6):523-36

Wolsko PM et al. 2005. Lack of herbal supplement characterization in published randomized controlled trials. Am J Med. 118(10):1087-93 [abstract]

Ernst E. 2007. Herbal medicine: buy one, get two free. Postgrad Med J. 83(984):615-6

Turner RB. 2009. Clinical trials of herbal treatments. Eval Health Prof. 32(4):410-6

Gilbert N. 2011. Herbal medicine rule book. Nature. 480(7378):S98-9

Zhang J, Wider B, Shang H, Li X, Ernst E. 2012. Quality of herbal medicines: challenges and solutions. Complement Ther Med. 20(1-2):100-6 [abstract]

Pan SY, Zhou SF, Gao SH, Yu ZL, Zhang SF et al. 2013. New perspectives on how to discover drugs from herbal medicines: CAM's outstanding contribution to modern therapeutics. Evid Based Complement Alternat Med. 2013:627375

van Breeman RB. 2015. Development of safe and effective botanical dietary supplements. J Med Chem. 8(21):8360-72

Tims M. 2016. Putting the cart before the horse: Toward the appropriate use of DNA methods for quality assurance in the herbal supplement industry. J Altern Complement Med. 22(8):588-90 [first page]

Rashrash M, Schommer JC, Brown LM. 2017. Prevalence and predictors of herbal medicine use among adults in the United States. J Patient Exp. 4(3):108-13

Gurley BJ, Yates CR, Markowitz JS. 2018. "…Not intended to diagnose, treat, cure or prevent any disease." 25 Years of botanical dietary supplement research and the lessons learned. Clin Pharmacol Ther. 104(3):470-83 [abstract]

 

Herbs for different conditions

Fugh-Berman A. 2003. “Bust enhancing” herbal products. Obstet Gynecol. 101(6):1345-9  [abstract]

Fiore K. 2009 Jan 14. No evidence herbal remedies help counter menopausal symptoms. MedPage Today

 

Herbs - hazards (general; see also specific items)

Ang-Lee MK, Moss J, Yuan C-S. 2001. Herbal medicines and perioperative care. JAMA. 286(2): 208-16 [abstract]

Ernst E. 2002. Toxic heavy metals and undeclared drugs in Asian herbal medicines. Trends Pharm Sci. 23(3): 136-9 [abstract]

Ernst E. 2003. Cardiovascular adverse effects of herbal medicines: A systematic review of the recent literature. Can J Cardiol. 19(7):818-27 [abstract]

Dasgupta A, Bernard DW. 2006. Herbal remedies: effects on clinical laboratory tests.  Arch Pathol Lab Med. 130(4):521-8

Gabardi S, Munz K, Ulbricht C. 2007. A review of dietary supplement-induced renal dysfunction. Clin J Am Soc Nephrol. 2(4):757-65

Cohen PA, Ernst E. 2010. Safety of herbal supplements: a guide for cardiologists. Cardiovasc Ther. 28(4):246-53

Tachjian A, Maria V, Jahangir. 2010. Use of herbal products and potential interactions in patients with cardiovascular diseases. J Am Coll Cardiol. 55(6):515-25

Hawkes N. 2012. Herbal medicines might be responsible for high incidence of urinary tract cancer. BMJ. 344:e2644 [beginning] (aristolochic acid)

Wong WW, Gabriel A, Maxwell GP, Gupta SC. 2012. Bleeding risks of herbal, homeopathic, and dietary supplements: a hidden nightmare for plastic surgeons?  Aesthet Surg J. 32(3):332-46

Posadzki P, Watson L, Ernst E. 2012. Herb-drug interactions: an overview of systematic reviews. Br J Clin Pharmacol. 75(3):603-18

Shi S, Klotz U. 2012. Drug interactions with herbal medicines. Clin Pharmacokinet. 51(2):77-104 [abstract]

Dunnick JK, Nyska A. 2013. The toxicity and pathology of selected dietary herbal medicines. Toxicol Pathol. 41(2):374-86

Anon. 2013. Heart trouble? 15 Herbal remedies to avoid. Health.com

Alissa EM. 2014. Medicinal herbs and therapeutic drug interactions. Ther Drug Monit. 36(4):413-22 [abstract]

Werner SM. 2014. Patient safety and the widespread use of herbs and supplements. Front Pharmacol. 12;5:142

Grollman AP, Marcus DM. 2016. Global hazards of herbal remedies: lessons from Aristolochia.  EMBO Rep. 17(5):619-25

Asher GN, Corbett AH, Hawke RL. 2017. Common herbal dietary supplement-drug interactions. Am Fam Physician. 96(2):101-7

Skalicka-Wozniak K, Georgiev MI, Orhan IE. 2017. Adulteration of herbal sexual enhancers and slimmers: The wish for better sexual well-being and perfect body can be risky. Food Chem Toxicol. 108(Pt B):355-64 [abstract]

Roytman MM, Poerzgen P, Navarro V. 2018. Botanicals and hepatotoxicity. Clin Pharmacol Ther. 104(3):458-69 [abstract]

Ernst E. 2018 Nov 5. Herbal medicines for the induction of labor? No, definitely not! Edzard Ernst

Farrington, Musgrave I, Byard RW. 2019. Potential adverse outcomes of herbal preparation use in childhood. Acta Paediatr. 108(3):419-22

Ekar T, Kreft S. 2019. Common risks of adulterated and mislabeled herbal preparations. Food Chem Toxicol. 2019 Jan;123:288-297 [abstract]

Fasinu PS, Rapp GK. 2019. Herbal interaction with chemotherapeutic drugs - a focus on clinically significant findings. Front Oncol. 9:1356

Novella S. 2020 May 27. Herbal products and pregnancy. Science-Based Medicine

 

Herbs - scientific critiques

Ernst E, Hung SK, Clement Y. 2011. NCCAM-funded RCTs of herbal medicines: an independent, critical assessment. Perfusion. 24(3):89-102

Pandolfi M, Zilletti L. 2012. Herbal medicine, Chaplin, and "The Kid". Eur J Intern Med. 23(4):330-2 [abstract]

Novella S. 2013. Herbs are drugs. Skeptical Inquirer. 37(2):28-9

Newmaster SG, Grguric M, Shanmughanandhan D, Ramalingam S, Ragupathy S. 2013. DNA barcoding detects contamination and substitution in North American herbal products. BMC Med. 11:222

O'Connor A. 2013 Nov 3. Herbal supplements are often not what they seem. New York Times

Owens C, Baergen R, Puckett D. 2014. Online sources of herbal product information. Am J Med. 127(2):109-15 [abstract]

McCartney M. 2014. How the UK drug regulator became the herbalists' marketeer. BMJ. 348:g3194 [preview]

Novella S. 2014 Apr 23. Herbal center at Cleveland Clinic. Science-Based Medicine

Crislip 2016 Jun 24. About Herbs: An app to avoid. Science-Based Medicine

Ernst E. 2018 Jun 18. Individualised (traditional) herbalism: best avoided, in my view. Edzard Ernst [menstrual problems]

Gavura S. 2018 Nov 1. Billions on herbal remedies – and for what? Science-Based Medicine

 

Herbs - specific (see text for additional references for reviews)

NIH Office of Dietary Supplements. Botanical supplement fact sheets [links for numerous specific herbs]

National Center for Complementary and Integrative Health. 2020. Aloe vera

Ernst E. 2016 Dec 21. Aloe vera for diabetes: a meta-analysis. If implemented, its conclusions could kill millions! Edzard Ernst

Hall H. 2018 Jul 10. Aloe vera. Science-Based Medicine

Federal Trade Commission. 2019 Oct 16. Aloe vera supplement seller barred from making misleading health claims. Press release

MedlinePlus. 2020. Arnica

MedlinePlus. 2020. Ashwagandha

National Center for Complementary and Integrative Health. 2020. Astragalus

MedlinePlus. 2019. Belladonna

MedlinePlus. 2020. Berberine

National Center for Complementary and Integrative Health. 2020. Bilberry

MedlinePlus. 2020. Bitter melon

National Center for Complementary and Integrative Health. 2020. Bitter orange

Kligler B. 2003. Black cohosh. Am Fam Physician. 68(1):1146

Walters P. 2006 Dec 18. Menopause study disputes herb treatment. Associated Press [black cohosh]

National Center for Complementary and Integrative Health. 2020. Black cohosh

Wobser RW, Takov V. 2019. Black cohosh (Actaea racemosa, black bugbane, black snakeroot, fairy candle). StatPearls

Farnsworth NR, Mahady GB. 2009. Research highlights from the UIC/NIH Center for Botanical Dietary Supplements Research for Women's Health: Black cohosh from the field to the clinic. Pharm Biol. 47(8):755-60

MedlinePlus. 2020. Black psyllium

MedlinePlus. 2019. Blessed thistle

MedlinePlus. 2020. Blond psyllium

Sutherland A, Sweet BV. 2010. Butterbur: An alternative therapy for migraine prevention. Am J Health-System Pharm. 67(9):705-11

National Center for Complementary and Integrative Health. 2020. Butterbur

MedlinePlus. 2019. Cascara sagrada

National Center for Complementary and Integrative Health. 2020. Cat's claw

National Center for Complementary and Integrative Health. 2020. Chamomile

Srivastava JK, Shankar E, Gupta S. 2010. Chamomile: A herbal medicine of the past with bright future. Mol Med Rep. 3(6):895-901.

MedlinePlus. 2019. Roman chamomile

National Center for Complementary and Integrative Health. 2020. Chasteberry

Federal Trade Commission. 2001 Jul 6. Latest FTC case in ‘Operation Cure.All’ focuses on safety risks of comfrey products promoted via Internet. Press release

National Center for Complementary and Integrative Health. 2020. Dandelion

MedlinePlus. 2020. Devil's claw

MedlinePlus. 2020. Dong quai

National Center for Complementary and Integrative Health. 2020. Echinacea

MedlinePlus. 2020. Eleuthero

National Center for Complementary and Integrative Health. 2020. Ephedra

Haller CA, Benowitz NL. 2000. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. New Engl J Med. 343(25):1833-8

Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA et al. 2003. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: A meta-analysis. JAMA. 289(12):1537-45 [abstract]

National Cancer Institute. 2015. Essiac/flor Essence(PDQ®) - Patient version

MedlinePlus. 2020. Eucalyptus

National Center for Complementary and Integrative Health. 2020. Elderberry [European elder]

Hall H. 2019 Dec 31. Elderberry elixir for the common cold. Science-Based Medicine

National Center for Complementary and Integrative Health. 2020. Fenugreek

National Center for Complementary and Integrative Health. 2019. Feverfew

National Center for Complementary and Integrative Health. 2016. Ginger

White B. 2007. Ginger: An overview. Am Fam Physician. 75(11):1689-91

Butt MS, Sultan MT. 2011. Ginger and its health claims: Molecular aspects. Crit Rev Food Sci Nutr. 51(5):383-93 [abstract]

National Center for Complementary and Integrative Health. 2020. Ginkgo

Koerner BI. 2007 Apr 25. Ginkgo biloba? Forget about it. Slate

Diamond BJ, Bailey MR. 2013. Ginkgo biloba: indications, mechanisms, and safety. Psychiatr Clin North Am. 2013;36(1):73-83 [abstract]

Ernst E. 2018 Dec 5. Ginkgo is harmless, I thought. But I was wrong: with the help of Chinese researchers, it could kill thousands. Edzard Ernst

MedlinePlus. 2020. American Ginseng

National Center for Complementary and Integrative Health. 2020. Asian Ginseng

MedlinePlus. 2019. Goji

National Center for Complementary and Integrative Health. 2020. Goldenseal

MedlinePlus. 2019. Guarana

MedlinePlus. 2019. Gymnema

National Center for Complementary and Integrative Health. 2020. Hawthorn

MedlinePlus. 2020. Hibiscus

MedlinePlus. 2020. Hops

MedlinePlus. 2020. Horny goat weed

National Center for Complementary and Integrative Health. 2016. Horse chestnut

MedlinePlus. 2020. Horsetail

National Center for Complementary and Integrative Health. 2020. Kava

Teschke R, Sarris J, Glass X, Schulze J. 2011. Kava, the anxiolytic herb: back to basics to prevent liver injury? Br J Clin Pharmacol. 71(3):445-8

Chang-Chien GC, Odonkor CA, Amorapanth P. 2017. Is kratom the new “legal high” on the block?: The case of an emerging opioid receptor agonist with substance abuse potential. Pain Physician. 20(1):E195-8

Ernst E. 2018 Feb 13. Kratom: a “herbal drug” with the potental to do more harm than good. Edzard Ernst

McGinley L, Zezima K. 2018 Jun 8. Kratom is hailed as a natural pain remedy, assailed as an addictive killer. The U.S. wants to treat it like heroin. Washington Post

Novella S. 2018 Aug 29. Kratom - an emerging herbal drug. Science-Based Medicine

Kaur H. 2019 Apr 13. More deaths have been associated with kratom than previously known, CDC study finds. CNN

Food and Drug Administration 2019 Jun 25. FDA issues warnings to companies selling illegal, unapproved kratom drug products marketed for opioid cessation, pain treatment and other medical uses

Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS. 2019. Kratom use and toxicities in the United States.  Pharmacotherapy. 39(7):775-7 [abstract]

McClurg L. 2020 Jan 13. The kratom debate: helpful herb or dangerous drug? NPR

National Center for Complementary and Integrative Health. 2020. Lavender

National Center for Complementary and Integrative Health. 2020. Licorice root

MedlinePlus. 2019. Maca

MedlinePlus. 2019. Mangosteen

MedlinePlus. 2020. Maritime pine

Nuzum DS, Gebru TT, Kouzi SA. 2011. Pycnogenol for chronic venous insufficiency. Am J Health Syst Pharm. 68(17):1589-1601 [first paragraph]

National Center for Complementary and Integrative Health. 2020. Milk Thistle

Abenavoli L, Izzo AA, Milic N, Cicala C, Santini A, Capasso R. 2018. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res. 32(11):2202-13 [abstract]

National Center for Complementary and Integrative Health. 2020. European mistletoe

Novella S. 2020 Jan 22. Black cumin - be skeptical. Science-Based Medicine [Nigella]

MedlinePlus. 2020. Olive

MedlinePlus. 2018. Pau d'arco

MedlinePlus. 2020. Pennyroyal

National Center for Complementary and Integrative Health. 2016. Peppermint oil

National Center for Complementary and Integrative Health. 2020. Red clover

MedlinePlus. 2020. Rose hip

National Center for Complementary and Integrative Health. 2016. Sage

National Center for Complementary and Integrative Health. 2016. St. John’s Wort

Ernst E. 2016 Oct 7. St John’s Wort for depression: the biggest success story of alternative medicine. Edzard Ernst

Booker A, Agapouda A, Frommenwiler DA, Scotti F, Reich E, Heinrich M. 2018. St John's wort (Hypericum perforatum) products - an assessment of their authenticity and quality. Phytomedicine. 40:158-64

Gavura S. 2018 Apr 5. St. John’s Wort for depression – A herbal remedy that works? Science-Based Medicine

Peterson B, Nguyen H. 2020 Jun 9. St. John's Wort. StatPearls

National Center for Complementary and Integrative Health. 2020. Saw palmetto

MedlinePlus. 2019. Senna

MedlinePlus. 2017. Slippery elm

MedlinePlus. 2019. Stevia

MedlinePlus. 2020. Black tea

National Center for Complementary and Integrative Health. 2016. Green tea

Mazzanti G, Di Sotto A, Vitalone A. 2015. Hepatotoxicity of green tea: an update. Arch Toxicol. 89(8):1175-91 [abstract]

Oketch-Rabah HA, Roe AL, Rider CV, Bonkovsky HL, Giancaspro GI, et al. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep. 7:386-402

National Center for Complementary and Integrative Health. 2016. Tea tree oil

National Center for Complementary and Integrative Health. 2016. Thunder god vine

National Center for Complementary and Integrative Health. 2020. Turmeric

Ernst E. 2016 Jun 22. Turmeric: lots of potential, but beware of the hype. Edzard Ernst

Hall H. 2020 Jun 16. Bad advertising for UPGRAID. Science-Based Medicine [turmeric product]

Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. 2017. The essential medicinal chemistry of curcumin. J Med Chem. 60(5):1620-37

Novella S. 2017 Jan 12. Curcumin hype vs reality. Neurologica

Anon 2020. Uva Ursi. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury

National Center for Complementary and Integrative Health. 2016. Valerian

MedlinePlus. 2020. Willow bark

MedlinePlus. 2019. Yerba mate

National Center for Complementary and Integrative Health. 2016. Yohimbe