HERBAL MEDICINE

Definitions

• Botanical - non-woody, seed-producing plants.
• Culinary arts - vegetable products used to add flavor or aroma to food.
• Medical - crude drugs of vegetable origin, used for treatment of disease states. Note: A limited number of botanical products such as prune juice or psyllium may qualify as either a food or a drug.

Popularity

• WHO in 1985 estimated that 80% of the world population relies on herbs for primary health care needs.
• Up to 30-40% of medical doctors in Germany and France rely on herbs as primary medications.
• A 1997 survey estimated that 12.1% of adults in the U.S. had used an herbal medicine in the past 12 months, as compared with 2.5% in a 1990 survey (JAMA. 1998. 280. 1569-1575).
• Data on use of dietary supplements in 1997-2002 indicated that18.6% of US adults in 2002 used herbal therapy (Tindle HA, et al. Altern Ther Health Med. 2005. 11. 42-49).
• Annual retail sales of botanicals have increased from $200 million in 1988 to an estimated $5.1 billion in the U.S. in 1997.  Sales recently have actually decreased to an estimated $4.2 billion in 2001.
• In 1998, annual sales were $151 million for ginkgo, $140 million for St. John's wort, $96 million for ginseng, $84 million for garlic, and $70 million for Echinacea.

General Principles

• Herbs are more dilute than over the counter or prescription drugs (Tyler V. Herbs of Choice. 1994. Pg 2).
• Herbs contain many active ingredients along with some physiologically inert substances (Tyler V. Herbs of Choice. 1994. Pg 3).
• Herbs are generally regarded as safer than prescription drugs. A meta-analysis of 39 prospective studies in U.S. hospitals found that in 1994, 2,216,000 hospitalized patients had an adverse drug reaction, and 106,000 had fatal adverse drug reactions (JAMA. 1998. 279. 1200-1205).
• Many years of use in folk medicine does not guarantee safety (i.e. comfrey).

Preparations of herbs

• Decoction – prepared by boiling the plant material in water for a period of time.
• Fluid extract - usually hydroalcoholic solutions of herbs, more concentrated than a tincture, with 1 ml usually representing 1 gram of herb.
• Infusion – prepared by pouring boiling water over the herb and allowing it to steep for a period of time.
• Solid extract – prepared by evaporating all of the solvent used to remove the active constituents from the herb; most concentrated form of an herb (but not necessarily bioavailable, depending on the amount of compression of the tablets, and the binders and fillers used in creating a capsule or tablet.
• Tincture – usually hydroalcoholic solutions of herbs; used when the active principles are not soluble in water or when a more concentrated product is required to allow adequate dosage. Concentration is usually 1-2 grams of herb per 10 ml.

Information on specific herbs

• Aloe - superior remedy for burns; grow plant in the home. Aloe vera gel at a dose of 2-6 tablespoons one to two times a day may help to heal peptic ulcers and may be useful in the treatment of Crohn's disease. This can be mixed with fruit juice.   Beware that ingestion of aloe products which contain latex or the whole leaf can cause diarrhea, GI irritation, and loss of electrolytes.  The element responsible for this is 'aloin' and some whole leaf extracts have the aloin extracted.
• Andrographis – effective treatment for URIs. A systematic review by the Natural Standard Research Collaboration of 7 clinical trials in 879 subjects found good evidence for effectiveness in treatment of URIs. The main limitation of the data is that the studies were sponsored by the manufacturer (Explore. 2006. 2[1]. 25-29).
• Aristocholia - definitely hazardous; should not be consumed at all.  Potent human carcinogen, and can cause kidney failure.  Traditional use in the U.S. as a digestive tonic and for treating snakebites.  A tragedy reported in 1992 in which there were at least 30 cases of kidney failure in Belgian women using a weight loss supplement actually involved upon careful chemical analysis inadvertant substitution of Aristocholia for Stephania, presumably based on these two herbs sharing the same Chinese common name, fangi. In 2008, this is a worldwide problem, with 128 reported cases in Belgium, 116 reported cases in China, and a few reported cases in many other countries (Kidney Int. 2008. 74. 158-169 as cited in Alt Med Alert. 2008. 11. 126-129).
• Arnica - external remedy for bruises, sprains, sore muscles (do not ingest). Do not apply to broken skin and do not ingest, because of systemic toxicity.
• Ashwagandha - Ayurvedic herb touted as an adaptogen and for treatment of multiple sclerosis.
• Astralgus - immune stimulant considered safe for long term use.  Dose is 500 mg (or 3 ml of 1:5 tincture) twice or three times a day.  Contra-indicated in persons taking coumadin.  In China the officially recognized daily dose is 9-30 grams.
• Bilberry
• Increases blood flow to the blood vessels of the eyes, and increases the capillary wall strength. 
• May slow the progression of cataracts and macular degeneration. 
• Dosage is 80-120 mg two to three times a day of a standardized product with 25% anthocyanosides.
• BEWARE bilberry is a very expensive herb ($500/kg in 2007) and thus adulteration with azo dyes is a possibility, as these dyes will be detected as anthocyanins on UV spectrophotometry. Anthocyanin content can be accurately detected by HPLC (Liva R. IMCJ. 2007. 6[5]. 31).
• Bitter orange - may be hazardous.  Used for centuries in TCM for digestive problems; often an ingredient in weight loss products since ephedra was banned, as the fruit contains synephrine, which has thermogenic properties. Bitter orange in weight loss formulas may induce the same adverse effects as Ephedra.
• Black cohosh (return to Home Page and click on ‘Menopause’ for detailed information on clinical trials and safety)
• Uses: traditionally used by Native Americans.
• Treatment of the symptoms of menopause.
• May also be beneficial in treatment of dysmenorrhea (recommended by German Commission E based on case reports), rheumatoid arthritis, low back pain, and muscle aches.
• Prostate cancer - there are no published clinical trials as of 2006, but there is promising in vitro and animal data (Alt Med Alert. 2007. 10. 5-8).
• Mechanism of action - neither the identity of the active compounds nor the mechanism of action of black cohosh is known.  More specifically, it is unknown whether black cohosh exerts its effect via estrogen receptors or through another mechanism (perhaps acting as a serotonin agonist, perhaps decreasing LH levels).  Formononetin was hypothesized to be an active ingredient, but is not present in Remifemin.
• Boldo – approved by German Commission E for dyspepsia, but potentially toxic as per Varro Tyler (Herbs of Choice. 1994) because the volatile oil in the leaves contains 40% ascaridole, a rather toxic compound.
• Butterbur
• Uses:
• Treatment of allergic rhinitis. In a two week RCT with 125 patients, shown at a dose of one tablet 4 times a day (carbon dioxide extract tablets, ZE 339) to work as well as cetirizine (Zyrtec) [BMJ. 2002. 324. 1-4].
• Migraines - dose is 50 mg 2-3 times per day for prophylaxis, 50 mg every 2 hours up to 6 doses per day for treatment of a migraine.
• CAUTION: Plants contain pyrrolizidine alkaloids (PA's) that may be toxic to the liver, so best to use pills with the PA's removed.
• Petasin is the active ingredient with spasmolytic and anti-inflammatory properties.
• Petadolex is the best studied brand name - this is a patented extract manufactured in Europe compliant with strict GMP; it is made from the rhizome of the plant and standardized to 15% petasins; the final product has <0.08 ppm PA's.
• Calamus - North American type is nontoxic but Indian type is potentially toxic secondary to cis-isoasarone, a carcinogen (J Am Pharm Assoc. 1996. 36. 29).
• Calendula - promotes wound healing if applied locally.
• Chamomile - digestive disorders, menstrual disorders, skin conditions, minor infections, sedation. Allergic reactions include tongue thickness, tight sensation in throat, angioedema of lips and eyes, diffuse pruritis, generalized urticaria, upper airway obstruction, pharyngeal edema, and abdominal cramps. Allergy to ragweed serves as a marker.  CamoCare is the best studied brand name.
• Chaparral - considered by some to be a valuable cancer treatment because its leaves contain a potent antioxidant, but many authorities recommend against its use because of the risk of liver damage.  Available data would suggest that the risk of adverse events is higher with the unextracted leaves than with the hydroalcoholic tinctures (Am J Gastroenterol. 1995. 90. 831-833), and that short-term internal use of liquid extracts should be safe to help reduce local inflammation and symptoms associated with colds, diarrhea, and urinary tract infections (Br J Phytother. 1993-1994. 3. 10-29).
• Cinnamon (Alt Med Alert. 2008. 11. 13-16)
• There are many different species of cinnamon.
• Traditional (historical) use
• Carminative (anti-gas), aide digestion, and improve appetite. Approved by German Commission E to treat loss of appetite, dyspeptic complaints such as mild spastic conditions of the GI tract, bloating, and flatulence.
• Diabetes – used this way in East Asia.
• Cinnamon and diabetes
• Mechanism of action – increases insulin sensitivity (J Am Coll Nutr. 2001. 20. 327-336) and stimulates release of insulin (Phytother Res. 2005. 19. 203-206).
• Safety – good safety in clinical trials
• Clinical trials are with Cassia cinnamon – several small RCTs with conflicting results.
• Dosages in clinical studies have ranged from 1-6 grams/day, and ½ teaspoon approximates 1 gram.
• Coltsfoot - cough suppressant, but pyrrolizidine alkaloids are toxic, so not recommended for oral use, or if used, only for a maximum of two weeks, and absolutely contra-indicated in people with liver disease.
• Comfrey - poultice for bed sores and diabetic ulcers (mix comfrey root in a blender with aloe vera gel). Many authorities recommend against oral use because of significant liver toxicity secondary to pyrrolizidine alkaloids (PA's).  Comfrey root has a much higher content of mucilage and allantoin, which stimulates cell proliferation, compared to comfrey leaves, but the root also has a much higher content of PA's.
• Cranberry
• Uses: Prevention and/or treatment of cystitis
• A 2009 Cochrane Review of cranberry for treatment of UTIs found that no published trials met inclusion criteria (Cochrane Database Syst Rev. 2009. CD001322).
• A 2008 Cochrane Review of cranberry for prevention of UTIs included 10 randomized or quasi-randomized clinical trials (n=1049) found “some evidence” that cranberry juice might decrease the number of symptomatic UTIs over a 12 month period, especially in women with recurrent UTIs (Cochrane Database Syst Rev. 2008. CD001321). An earlier 2004 Cochrane Review identified 5 trials with 304 patients which met inclusion criteria, but overall methodologic quality was only fair, leading the authors to conclude that there is no conclusive evidence to support this use of cranberry (Cochrane Database Syst Rev. 2004. CD001321). 
• However, a 12 month RCT in 150 women found a 20% reduction in the absolute risk of infection in women treated with cranberry/lingonberry juice compared with the probiotic supplementation group and a no-intervention group (BMJ. 2001. 322. 1571).
• Another 12 month RCT in 150 women found that cranberry juice and cranberry extract significantly decreased the number of patients having at least one symptomatic UTI per year (Can J Urol. 2002. 9. 1558-1562).
• A 12 month RCT in 221 premenopausal women with recurrent UTI’s found that TMP-SMX 480 mg once a day is more effective than cranberry capsules 500 mg twice a day at prevention of recurrent UTI’s, and that both regimens were equally well tolerated. Downside of antibiotic prophylaxis was a much higher rate of bacterial resistance during the trial (Arch Intern Med. 2011. 1270-1278). An invited commentary notes that bioavailablity of cranberry extract is much lower than TMP-SMX, and that higher doses might be more effective; dosing studies of cranberry extract have not been performed (Arch Intern Med. 2011. 1279-1280).
• Mechanism of action – proanthocyanidins prevent adherence of bacteria to the bladder wall (JAMA. 1988. 260. 1465), antioxidant and anti-inflammatory effects too.
• Safety
• No significant side effects (high doses can cause GI side effects, and long term use of high amounts might increase risk of uric acid kidney stones) or known significant drug interactions (specifically, a clinical study looking at interaction of a cranberry juice cocktail with amoxicillin and cefaclor found no significant overall clinical effect [Antimicrob Agents Chem. 2009. 53. 2725-2732]).
• Interaction with Coumadin – although reported in case reports, randomized clinical trials using quantities of cranberry juice up to 600 ml (2.5 cups) show no evidence of an interaction (Am J Med. 2010. 123. 384-392).
• Dosage is 8 ounces of unsweetened juice three times per day or 400 mg of powdered cranberry extract twice a day.
• Popularity – a 2007 NHIS survey reported that about 1.6 million Americans used cranberry within the past year.
• Curcumin - anti-inflammatory, the active ingredient in turmeric. 
• Dosage is 400 mg three times a day.
• Safety – many extracts are contaminated with ethylene dichloride, a Class I solvent (probable human carcinogen), based on testing done by Vital Nutrients. This solvent is not mentioned in the COA for many batches of raw material, even though testing shows it is present, often in substantial concentrations (Liva R. IMCJ. 9 [5]. 50-54).
• Devil's claw
• Useful for treatment of osteoarthritis pain based on several small studies reported in France, and low back pain based on a Cochrane Review (Cochrane Database Syst Rev. 2006. CD004504). 
• Dose is 2.0 to 2.4 gram/day of a powdered extract containing 0.3 to 0.7 grams of harpagoside.
• DGL (deglycyrrhizinated licorice) - treats peptic ulcer disease, indigestion.  Mechanism of action is related to strengthening the lining of the stomach, making it less susceptible to damage from acid.
• Dong quai - female tonic, believed to be useful for treatment of menopausal symptoms.  A recent study however showed no efficacy for this herb when used alone for the treatment of menopause.  Dose is 500-900 mg or 30 drops of tincture 3 times a day of a standardized extract containing 0.8% to 1.1% ligustilide.  Some herbalists recommend limiting use to 3 months.  May elevate the Pro Time in patients on coumadin, so relatively contra-indicated with coumadin.
• Echinacea
• There are 9 species in the genus; commercially available herbal medications are produced from 3 species: Echinacea augustifolia, Echinacea pallida, and Echinacea purpurea.  Furthermore, different products use different parts of the plants, mostly the roots.  Thus there is considerable variability amongst products, and this makes the research on Echinacea difficult to evaluate.   The most common product in this country is the root of E. purpurea.
• Uses:  Over 400 scientific studies worldwide.
• Treatment and/or prevention of upper respiratory infections. 
• Historically, majority of scientific study occurred in Germany.  Four German Commission E monographs were published on Echinacea, and two were positive (E. pallida root and E. purpurae herb) while the two others concluded that there was insufficient evidence to establish efficacy (E. angustofilia root and E. angustofilia/E. pallida herb).  
• A Cochrane review of 16 randomized trials including 3396 patients (Cochrane Database Syst Rev. 2000. CD000530) found that the methodologic quality of the studies as assessed by Jadad score varied, with some of good quality.   In the 5 trials of prevention that had a placebo control group, the results were inconclusive. Each of these trials tested a different Echinacea product.  In one of these trials, which included 302 patients, Echinacea was no better than placebo (Arch Fam Med. 1998. 7. 541-545). The three prevention trials with control groups that received no treatment (as opposed to placebo treatment) suggested a beneficial effect.  Of the 8 treatment trials in this review, all placebo controlled, 6 did show a favorable effect for the herb. Various Echinacea products were used in these trials. An updated Cochrane review concluded that inconsistencies in the data persist (Cochrane Database Syst Rev. 2006. CD000530).
• A meta-analysis of 14 RCTs which included 1356 patients in 9 trials evaluating a preventive effect and 1630 patients in 7 trials evaluating treatment effect showed a 58% lower odds of contracting an URI and a beneficial effect on duration of symptoms in those with URIs (Lancet Infect Dis. 2007. 7. 473-480).
• One of the positive trials was a randomized, controlled trial with 160 patients who received either placebo or 900 mg of Echinacea daily in the form of 90 drops of a root extract. The active treatment group had resolution of upper respiratory symptoms in 9 days compared with 13 days in the placebo group (Complement Ther Med. 1997. 5. 40-42). 
• Since this Cochrane Review was completed, another positive placebo-controlled treatment trial has been published - this one including 80 patients treated with Echinacin, EC31J0 (Arzneimittelforschung. 2001. 51. 563-568).
• HOWEVER, methodologically rigorous RCT in 148 students with common colds of recent onset testing an encapsulated mixture of Echinacea purpurea herb (25% and root (25%), and E. angustifolia root (50%) taken in 1 gram doses six times on day 1 and 3 times on each subsequent day up to 10 days showed no detectable benefit on the severity or duration of self-reported symptoms (Ann Intern Med. 2002. 137. 939-946).
• A RCT of 707 URIs in 407 children ages 2-11 treated with Echinacea purpurea for a maximum of 10 days showed no benefit for the herb in treatment of acute URIs, but an increased risk of rash.  Note that there was a decrease in the risk of recurrent URIs in the treatment group (a secondary endpoint).  Note that this study used the flower of the plant whereas most studies use the root, and this may be the explanation for the higher incidence of rash (JAMA. 2003. 290. 2824-2830).
• A RCT in 282 adults instructed to take Echinacea at the first sign of cold-related symptoms, 10 doses on the first day and 4 doses on each subsequent day for one week, found that daily symptom scores were 23.1% lower with Echinacea (J Clin Pharm Ther. 2004. 29. 75-83). A review of 322 published articles on Echinacea found that only 2 trials met all 11 inclusion criteria, and neither showed a difference from placebo, but 7 additional trials met most of the inclusion criteria, and 6 of these 7 were positive (Clin Infect Dis. 2005. 40. 807-810).
• A RCT in 437 volunteers who upon testing were susceptible to rhinovirus type 39 found no significant treatment effects for any of the 3 E. angustofolia root products used in this trial which involved direct nasal challenge with rhinovirus type 39. The methodology in this study was good with the exception that the typical dose of E. angustofilia root is 3 grams per day and this study used only 900 mg/day! (N Engl J Med. 2005. 353. 341-348).
• A RCT in 719 patients with new onset URI symptoms consistent with a “common cold” in which the treatment group received either Echinacea tablets containing a mix of E purpurea root 675 mg and E angustifolia root 600 mg concluded that there was not a significant difference in illness duration or illness severity in the treatment versus placebo group. Mean illness duration was 6.34 days in the treatment group, compared with 6.87 days in the placebo group (P= 0.075). The dose of Echinacea (Medi Herb product) was 2 tablets four times a day for the first day (total dose first day of 10.2 grams dried Echinacea root), followed by 1 tablet four times a day for the next 4 days (total dose first day of 5.1 grams dried Echinacea root on days 2-5). If in fact the 0.5 day reduction in duration was real and not due to chance, prior research by this group at U of Wisconsin suggest that no more than 1 in 4 people would consider this level of benefit worthwhile, considering the cost, inconvenience, and possible adverse effects of Echinacea (Ann Intern Med. 2010. 153. 769-777).
• May be useful in treatment of abscesses, burns, eczema, leg ulcers, and wounds.
• Dr. Jacob Teitelbaum advocates as part of a regimen for adrenal insufficiency in those with chronic fatigue syndrome - 6 weeks on and 2 weeks off. Reference regarding a stimulating effect on adrenal gland is Arzneimittel Forschung. 1953. 3. 133-137.
• Long term use may be associated with tachyphylaxis - best not to use for more than two weeks at a time.
• Mechanism of action - stimulation of the immune system (J Altern Complement Med. 1995. 1. 145-160; Immunopharmacology. 1997. 35. 229-235), local anesthesia, anti-inflammatory, hormonal, antiviral, and free-radical scavenging activities. 
• Potentially active ingredients include polysaccharides, glycoproteins, alkamides, and flavonoids.  Based on the mechanism of action, considered contraindicated in patients on prescription corticosteroids, and relatively contraindicated in autoimmune disorders (multiple sclerosis, lupus).
• There is some data that the stimulation of the immune system is a function of alkylamides in Echinacea – these compounds are found in roots of Echinacea angustofilia and Echinacea purpurea, and are not found in the stem or flower – this could explain some of the variable outcomes in various trials of Echinacea using different species and different parts of the plant (Bone K. The Best in Phytotherapy in 2004: Solving the Echinacea Puzzle. Townsend Letter. Feb-March 2005).
• Safety - Adverse effects are rare and consist mostly of allergic reactions, but there are documented cases of severe anaphylactic or asthmatic reactions.  Data would suggest that atopic females are at greatest risk for severe allergic reactions (Ann Allergy Asthma Immunol. 2002. 88. 42-51). A prospective study of Echinacea exposure during pregnancy found no increased risk for major malformations in 206 women who used the herb (Arch Intern Med. 160. 3141-3143. 20000.  May cause rashes, asthma, anaphylaxis, infertility and hepatotoxicity (anecdotes, but no published data).  Products may contain organochlorine pesticides including some that have been banned in the US (Bull Environ Contam Toxicol. 2001. 66. 150). May be a weak inhibitor of the cytochrome P450 3A4 system, so numerous herb-drug interactions are possible.
• Dosage - varies with the preparation of the herb.  0.75-1.5 ml of tincture daily, 6-9 ml of pressed juice daily, 900-1000 mg of freeze dried extract in capsules 3-4 times a day, or 6-8 ounces of tea four times a day (Alternative Medicine Alert. 2004. 7. 41-44). In some studies the tincture contains 22% ethanol and 2.4% fructofuranosides; in other studies the powdered extract contains 3.5% echinacosides.  Commercial preparations are typically not standardized to any particular component because the active component(s) has not yet been identified.
• Quality
• A study of 59 Echinacea products from retail stores analyzed by thin layer chromotography showed that 6 contained no measurable Echinacea and only 9 of the 21 preparations labelled as standardized extracts actually contained in the sample the content listed on the label. Overall, the assay results were consistent with the labelled content in only 31 of the59 preparations (Arch Intern Med. 2003. 163. 699-704).
• Consumer Lab tested 11 brands in 2004, and 5 failed the test, meaning the contents of the bottle were not as indicated on the label.
• Echinaguard is the best studied brand name.
• Elderberry - influenza.  Long history of use in folk medicine.
• In a RCT in China in 64 patients with more than 3 influenza like symptoms (fever, headache, myalgias, cough, nasal mucous discharge, nasal congestion) who were randomized within 24 hours to a 175 mg Elderberry extract lozenge (brand name DART Immune) versus placebo 4 times a day for 2 days, those randomized to the Elderberry had more rapid resolution of symptoms. The rate of complete symptom relief at 48 hours was 28% with Elderberry versus 0% with placebo; the rate of partial symptom relief at 48 hours was 88% with Elderberry versus 16% with placebo. A limitation of this trial was that those randomized to elderberry had higher symptom scores at baseline (Online J Pharmacol Pharmacokin. 2009. 5. 32).
• In a RCT in Norway in 60 symptomatic influenza patients from 4 primary care sites, Sambucol 15 ml four times a day starting within 48 hours of symptom onset, and for 5 days, was associated with more rapid improvement in aches and pains, quality of sleep, mucous discharge, and nasal congestion by visual analog scale. The scores between the placebo and treatment groups began to diverge on day 4 , such that the magnitude of improvement in symptoms seen in the treatment group on days 4-5 was not seen in the placebo group until days 7-8. In terms of a global evaluation score of symptoms, a significant improvement was seen in the active treatment group by a mean of 3.1 days, but not in the placebo group for a mean of 7.1 days. Influenza A was isolated from 54 of the patients and influenza B was isolated from the other 6 (J Int Med Res. 2004. 32. 132-140).
• In a previous randomized study in 27 Israeli adults and children, Sambucol, in a dose of 60 cc per day for adults and 30 cc per day for children, 93.3% of the treatment group showed significant symptom improvements within 2 days, whereas it was day 6 before 91.7% of the patients in the placebo group showed significant improvement in symptom scores (J Alt Compl Med.  1995. 1. 361-369).
• Eleutherococcus senticosus – Russian ginseng – see ‘ginseng’ below. Most research has been done in Russia, in uncontrolled trials.
• Ephedra - effective bronchodilator, and some data on efficacy for weight loss.  Banned in 2004 by the FDA based on concerns about safety - see above in outline under "DSHEA - safety - the story of ephedra" for details.
• Evening primrose (Oenothera biennis) - oil contains GLA, an essential fatty acid in the omega 6 family of oils.  GLA has anti-inflammatory effects.  Borage oil and black currant seed oil are actually better sources of GLA. Contrary to anecdotes, current data indicates it is ineffective for PMS (premenstrual syndrome) and eczema..  May be effective for cystic mastalgia, diabetic neuropathy, rheumatoid arthritis.  Dosage is 3-6 grams a day of evening primrose oil, or roughly 300-600 mg GLA.
• Fenugreek - seeds lower blood sugar and improve lipid profiles in diabetics (Eur J Clin Nutr. 1988. 42. 939-944). Supplements made from the dried leaf alone will not provide the desired effects.  Take as a tea three times a day, boiling a teaspoon of (debittered) seeds in 1 cup of water or take 500 mg three times a day with meals. Contraindicated in pregnancy, with peanut allergy, and in conjunction with prescription coumadin.
• Feverfew
• Uses: Prevention of migraine headaches (Cephalagia. 1998. 18. 704-708; BMJ. 1985. 291. 569-573; Lancet. 1988. 2. 189-192; Phytother Res. 1997. 11. 508-511).  A systematic review which examined 6 randomized, controlled trials found positive and negative trials, but concluded that the results of randomized controlled clinical trials favor feverfew over placebo (Public Health Nutr. 2000. 3. 509-514).  May also be useful in the treatment of fever, migraine headaches, and rheumatoid arthritis.
• Dosage: 50 mg twice a day.  Capsules should have at least 0.2% parthenolide/capsule. The daily dose of parthenolide for prevention of migraines should be 0.2 - 0.5 mg.
• Mechanism of action:  Due in part to suppression of prostaglandin production, so concomitant use of NSAID's may reduce effectiveness. May take 4-6 months of use to note a positive effect.
• Quality: Significant variation amongst brands. A Canadian study showed that no North American feverfew product analyzed contained the recommended minimal amount of 0.2% parthenolide believed to be required for effectiveness (Journal of Natural Products. 1991. 54. 1516-1521).
• Safety:  A 10% to 18% incidence of mouth ulcers reported with chronic use.  Contraindicated in those allergic to ragweed, chamomile, yarrow. Inhibits platelet activity, so relatively contraindicated with coumadin use.
• Garlic (Alt Med Alert. 2008. 11. 17-20)
• Uses: Thousands of papers on garlic in peer reviewed scientific literature.
• Anti-infective properties against bacteria, viruses, parasites, and fungi.
• Lowers blood pressure slightly, based on a systematic review and meta-analysis of 11 RCTs with a n=525 (BMC Cardiovasc Disord. 2008. 8. 13).
• Lowers cholesterol [go to Home Page and click on Cholesterol for detailed information with references]
• Slows the rate of progression of atherosclerosis
• Decreases blood clotting
• May protect against cancer, including cancers of the colon, stomach, prostate, and breast
• May lower blood sugar, may forestall cataracts, may increase libido.
• Mechanism of action:  Intact garlic cells contain alliin, an odorless sulfur-containing amino acid.  When garlic is crushed, chewed, or sliced, the alliin is exposed to the enzyme alliinase located in neighboring cells, and allicin, an unstable odiferous compound is formed.  Allicin is converted to other sulfur compounds such as ajoene and allyl sulfides. Alliinase is inactivated by acids, so alliin in garlic is NOT converted to allicin in the stomach (it can be converted in the mouth though).
• Dosage: The daily dose should be at least 10 mg of alliin or 4000 micrograms of total allicin potential (approximately equal to 1 clove of fresh garlic).  Fresh garlic contains approximately 1% alliin.  Dose of standardized powder containing 1.3% alliin is 200-400 mg three times a day.
• Safety:
• Inhibits platelet aggregation, so relatively contraindicated with coumadin use, but no data of harm when used with coumadin (J Nutr. 2006. 136[suppl 3]. 793S-795S).
• There is no evidence on an interaction with coumadin.
• Induces hepatic cytochrome P450 3A4, so herb-drug interactions are a possibility. 
• Allergy to garlic may affect 1% of people when it is used at a therapeutic dose (Mol Nutr Food Res. 2007. 51. 1386-1397).
• Discontinue at least 7 days before surgery.
• Kwai is the best studied brand name.
• Gentian - digestive remedy, possible appetite stimulant.
• Germander - definitely hazardous; should not be consumed at all.  Can cause hepatic failure; with good documentation of this adverse effect based on positive rechallenges in numerous cases (Ann Intern Med. 1992. 117. 129-132; CMAJ. 1996. 154. 1689-1692).
• Ginger
• Knee osteoarthritis - A 6 week RCT with 261 subjects which used 255 mg per day of a patented ginger extract, EV.EXT 77 reported effectiveness similar in magnitude to that reported with NSAIDs (Arthritis Rheum. 2001. 44. 2531-2538).  HOWEVER another RCT with 3 treatment periods each of 3 weeks, comparing ginger, ibuprofen, and placebo found no overall difference between ginger extract and placebo (Osteoarthritis Cartilage. 2000. 8. 9-12).
• Motion sickness – superior to Dramamine and placebo in one study (Lancet. 1982. 1. 655-657), but other studies have been negative (Acta Otolarynogol. 1988. 105. 45-49; Pharmacology. 1991. 42. 111-120).
• Nausea
• Chemotherapy induced nausea – mixed data. Positive results in a trial of 60 children and young adults who received 1000-2000 mg of ginger in 3 divided doses, in addition to conventional antiemetic therapy (Pediatr Blood Cancer. 2011. 56. 234-238). However, addition to a standard regimen not associated with added benefit (Int J Gynecol Cancer. 2004. 14. 1063-1069).
• Clinical nausea and vomiting – a systematic review of 11 RCTs found insufficient data to draw conclusions (Br J Anaesth. 2000. 84. 367-371).
• Nausea of pregnancy – a review of 33 published studies in which 6 (n=675) met criteria for inclusion showed that ginger was superior to placebo in 4 studies and equivalent to vitamin B6 in the other two studies (Obstet Gynecol. 2005. 105. 849-856). A previous Cochrane review also found ginger beneficial (Cochrane Database Syst Rev. 2003. CD000145).
• Postoperative nausea – a meta-analysis of 5 RCTs (n=363) found ginger more effective than placebo (Am J Obstet Gynecol. 2006. 194. 95-99).
• Vertigo (J Otorhinolaryngol Relat Spec. 1986. 48. 282-286).
• Dosage is 250 mg of dried root 4 times a day.
• Mechanism of action – inhibits COX 1 and COX 2 and also inhibits 5-lipoxygenase and inhibits inducible genes which encode for inflammatory cytokines and chemokines (J Med Food. 2005. 8. 125-32).
• Safety in pregnancy is debated, with the American Botanical Council asserting based on a literature review that it is safe in pregnancy (German Commission E came to a different conclusion that ginger is not safe in pregnancy).
• Safety
• Inhibits thromboxane synthetase, and therefore prolongs bleeding time, so relatively contraindicated with coumadin use. Inhibits thromboxane synthetase (Indian J Med Sci. 2001. 55. 83-86). It does not, however, affect INR, based on data from an open label, three-way, randomized crossover trial in 12 men (Br J Clin Pharmacol. 2005. 59. 425-432).
• Suppresses CYP2D6, and 5-10% of Caucasians have a genetic polymorphism such that this enzyme is sluggish (N Engl J Med. 2003. 348. 529-537). In these individuals, co-administration of drugs metabolized by this enzyme can result in toxic drug reactions.
• Ginkgo biloba
• Uses:
• Dementia treatment
• North American EGb Study Group - a 52 week RCT in 309 patients reported significant improvement in mean scores for cognitive function and daily behavior, but not the score on the Clinical Global Impression Scale.  At 26 weeks the data would suggest that at least 6 patients would need to be treated to obtain a clinically meaningful change in one patient. A limitation of this study is that only 50% of the ginkgo group and 38% of the placebo group completed the study. There were two different patterns of response in this study – patients with baseline mild cognitive impairment by MMSE score showed improvement with ginkgo whereas more severely demented patients by MMSE score showed only stabilization of the cognitive decline (JAMA. 1997. 278. 1327-1332).
• A meta-analysis of high methodologic quality of four RCT's of ginkgo to treat Alzheimer's disease (total of 212 patients) also found benefit for treatment with ginkgo (Arch Neurol. 1998. 55. 1409-1415).
• A systematic review of adequate quality included 9 RCT's (1947 patients), of which of which 3 had a Jadad score of 5/5 for quality, and found that results were positive in 8 of the 9 studies, including the 3 of highest quality (Clin Drug Investigation.  1999. 17. 301-308). 
• A review of published placebo-controlled efficacy studies of at least 6 months' duration found that ginkgo extract and second generation cholinesterase inhibitors were equally effective in treating mild to moderate Alzheimer's dementia (Phytomedicine. 2000. 6. 393-401). 
• A 2002 Cochrane review of 33 trials found promising evidence of improvements in cognition and function with ginkgo (Cochrane Database Syst Rev. 2002. 4:CD003120).
• Negative trial - a 6 month regulatory trial of 513 patients with mild to moderate Alzheimer’s disease sponsored by Schwabe Pharmaceuticals failed to demonstrate efficacy (Curr Alzheimer Res. 2005. 2. 541-551).
• A 24 week RCT comparing the EGb 761 extract of ginkgo, 160 mg daily, with Aricept 5 mg daily in patients with mild to moderate dementia found the two equal in efficacy (Eur J Neurol. 2006. 13. 981-985).
• A 2007 Cochrane review of 35 trials and 4247 participants found “inconsistent and unconvincing” evidence for clinically significant benefits in individuals with dementia or cognitive impairment. Most of the trials analyzed were short term trials, 6-26 weeks in duration (Cochrane Database Syst Rev. 2007. 2. CD003120).
• Negative trial - RCT in 118 participants age 85 or older, with mild cognitive impairment or dementia, using 240 mg/day of ginkgo, and with 42 months of follow up. There were more ischemic strokes and TIA’s in the treatment group (Neurology. 2008. 70. 1809-1817).
• Negative trial - RCT in a community setting in Britain in patients with mild to moderate dementia, using 120 mg/day of ginkgo (Int J Geriatr Psychiatry. Epub 6/9/08)
• Overall conclude that the evidence for gingko in treatment of dementia is mixed, with the more recent studies mostly negative.
• Dementia prevention/memory enhancement
• ‘Early data’ promising - a systematic review of high quality found 40 controlled trials, but only 8 were deemed by the authors of the systematic review to be of high quality.  Seven of the eight high quality studies showed positive effects of ginkgo on cognitive function, compared to placebo (Br J Clin Pharmacol. 1992. 34. 352-358). 
• A RCT of ginkgo 180 mg daily in 262 cognitively intact (i.e. MMSE > 26/30) community-dwelling volunteers over age 60 found both objective and subjective evidence of benefit (Human Psychopharmacol. 2002. 17. 267-277). 
• HOWEVER, another six week RCT of ginkgo 40 mg three times a day in 230 men and women over age 60 without baseline abnormalities in cognitive function showed no benefit. This study though was methodologically flawed in that there were baseline differences between the placebo and treatment groups and the placebo was readily distinguishable from the ginkgo in that one was a pill and the other was a capsule (JAMA. 2002. 288. 835-840).
• A meta-analysis of 8 trials did not find evidence for cognitive benefits in non-cognitively impaired participants younger than age 60, treated for up to 13 weeks (Hum Psychopharmacol. 2007. 22. 265-278).
• GEM Trial - Ginkgo biloba (EGb 761) 120 mg twice a day ineffective for dementia prevention in a multi-center RCT conducted in 5 academic medical centers, and sponsored by NCCAM. The 3069 participants were community volunteers (recruited by the use of voter registration records) ages 75 or older, with normal cognition (n=2587 or mild cognitive impairment (n=483) at baseline. Mean follow up was 6.1 years. Subgroup analysis showed no benefit in either the large group that was cognitively intact at baseline or the smaller group that showed mild cognitive impairment at baseline (42% of the 383 participants with mild cognitive impairment at baseline developed dementia over the 6 years of follow up. Additional subgroup analysis showed that in the 25% of patients with cardiovascular disease at baseline, there was actually an increased risk of developing dementia in the ginkgo treatment group (RR 1.56, P=0.006). There was a non-statistically significant increase in the risk of hemorrhagic stroke in the treatment group. Secondary outcome measures in this study included (1) cardiovascular serious events - no difference between treatment and placebo group, (2) total mortality - no difference between treatment and placebo group, (3) overall cognitive decline - results not yet reported, and (4) functional disability - results not yet reported (JAMA. 2008. 300. 2253-2262 and editorial 2306-2308). A follow up report which included the results of much more detailed cognitive testing also failed to identify benefit (JAMA. 2009. 302. 2663-2670).
• Intermittent claudication
• A meta-analysis of good quality pooled the results of 8 RCT's (413 patients), most of which received a Jadad score of 4/5 or 5/5 for quality, and found that ginkgo recipients walked 34 meters farther without pain compared with controls (Am J Med. 2000. 108. 276-281).
• In the largest RCT, which included 111 patients with angiographically proven PVD, after 24 weeks the mean pain free walking distance increased by 45 meters in the ginkgo group and 21 meters in the placebo group; the maximum walking distance increased by 61 meters in the ginkgo group and 25 meters in the placebo group (Vasa. 1998. 27. 106-110).
• This positive effect is similar in magnitude to the positive effect seen for the prescription drug pentoxifylline, but smaller in magnitude to the positive effect seen with regular walking exercise. 
• While these results are statistically significant, they are of questionable clinical significance.
• Tinnitus
• A systematic review of adequate quality summarized the results of 5 RCT's (621 patients) with 4 of the 5 studies scoring high for quality by Jadad score, and found that there was a moderate but statistically significant benefit on the perceived loudness of tinnitus in those who took ginkgo for 12 weeks (Clin Otolaryngol. 1999. 24. 164-167).
• A more recent 12 week RCT of ginkgo 50 mg three times a day for in 978 subjects showed no efficacy, but this trial used extract LI 1370, and not EGb 761 (BMJ. 2001. 322. 73). 
• HOWEVER, a meta-analysis of 6 RCTs found no significant benefit (Clin Otolaryngol. 2004. 29. 226-231); and a Cochrane Review also found no data to indicate that ginkgo is effective for tinnitus.  This review identified 12 trials, but 10 were excluded on methodological grounds (Cochrane Database Sys Rev. 2004. 2. CD003852).
• Sexual dysfuntion secondary to SSRI drugs (Prozac, Zoloft, Paxil, Celexa)
• In a double-blind study of the women's formulation of a proprietary multi-ingredient supplement marketed as ArginMax (Daily Wellness Company), which contains L-arginine, ginkgo, and a number of other dietary supplements, 73% of the 77 participants reported improvements in overall sexual satisfaction compared to 37% of the placebo users (J Sex Marital Ther. 2001. 27. 541-549). 
• In an open trial of ginkgo extract 60-120 mg per day, 91% of the 33 study women and 76% of the 30 study men reported "enhancing effects" on all phases of the sexual response cycle (J Sex Marital Ther. 1998. 24. 139-143).
• Atherosclerosis - may dissolve plaque (Atherosclerosis. 2007. 192. 438-444).
• May be useful in treatment of acrocyanosis, asthma, depression, erectile dysfunction, headaches, hypoxia, macular degeneration (Cochrane Database Syst Rev. 2003. 2:CD001775), mountain sickness, post-phlebitic syndrome, and Raynaud's disease.
• Dosage - The dosage in clinical trials ranges from 40 mg 3 times a day to 120 mg twice a day, of a standardized extract with 22% - 27% ginkgo flavone glycosides and 5% - 7% terpene lactones, with dosages in some clinical trials as high as a total of 320 mg/day. Product should contain less than 5 ppm ginkgolic acids, as they are allergenic
•  Mechanism of action - In vitro and in vivo studies suggest antiedemic, antihypoxic, free-radical scavenging, antioxidant, metabolic, antiplatelet, hemorheologic (similar to pentoxifylline), and microcirculatory actions.
• Safety
• Adverse effects are usually mild, transient, and reversible, and include headache, nausea, and vomiting.
• A Cochrane Review of ginkgo for dementia found no excess side effects compared to placebo (Cochrane Database Syst Rev. 2002. CD003120). 
• Relatively contraindicated with heparin, coumadin, aspirin, NSAID's, because Ginkgolide B is a potent inhibitor of platelet aggregating factor.  
• There are published case reports of subdural hematoma, hyphema, subarachnoid hemorrhage, and intracerebral hemorrhage with gingko. HOWEVER, in a 14 day RCT in 32 healthy volunteers, Ginkgo biloba extract (EGb 761) at daily doses of 120 mg, 240 mg, and 480 mg did NOT alter platelet function or coagulation (Clin Lab Haematol. 2003. 25. 251-253), and a meta-analysis shows that ginkgo does not increase the risk of bleeding (Pharmacotherapy. 2011. 31. 490-502).
• Ginkgo does not affect INR, based on an open label, three-way, randomized crossover trial in 12 men (Br J Clin Pharmacol. 2005. 59. 425-432).
• It may diminish the effectiveness of anticonvulsants, and may cause infertility.
• Popularity - An estimated 2 billion daily doses (120 mg) have been sold from 1983-2003.
• The best studied brand names include Ginkgold, Ginkoba, and Ginkai.  The extract used in most clinical trials is EGb 761.
• Ginseng
• This is a label which is not precise, because there are many different types of ginseng.  These include Asian ginseng (Panax ginseng), Siberian or Russian ginseng (Eleutherococcus senticosus), American ginseng (Panax quinquefolius), Vietnamese ginseng (Panax vietnamensis), and Japanese ginseng (Panax japonicus).
• Uses: A systematic review of adequate quality of 16 RCT's of any type of ginseng extract for diverse indications, most of low methodologic quality by Jadad score, found that the evidence from the few high quality clinical studies did not support the use of ginseng for any indication (Eur J Clin Pharmacol. 1999. 55. 567-575). Some experts have critiqued the conclusions of this systematic review because different species of ginseng were grouped together and because 5 of the 6 studies with a Jadad score of 4/5 were actually positive (Herbalgram. 2001. 52. 20).
• Adaptogen - build up resistance to stress. Theoretical rationale, and historical use.
• Cancer prevention - an epidemiologic study of 4634 inhabitants of a ginseng-growing region of Korea found that persons who regularly consumed fresh Korean ginseng had a significantly reduced risk of cancer of 0.31 (Int J Epidemiol. 1998. 27. 359-364).
• Diabetes:
• Panax ginseng 100-200 mg per day shown in a trial with 36 type II diabetics to lower fasting blood sugar, and at the 200 mg dose to lower glycosylated hemoglobin (Diabetes Care. 1995. 18. 1373-1375).
• American ginseng (Panax quinquefolius) 3 grams shown in one small study with 10 nondiabetic subjects and 9 Type II diabetic subjects to reduce postprandial hyperglycemia (Arch Intern Med. 2000. 160. 1009-1013).
• American ginseng at doses of 3, 6, and 9 grams, taken 40 minutes before a 25 gram oral glucose challenge shown in another small study with 10 nondiabetic subjects to significantly lower mean blood glucose levels at 30, 60, and 90 minutes post challenge, relative to placebo (J Am Coll Nutr. 2000. 19. 738-744).
• Enhance psychological function - data is mixed (Am Fam Physician. 2003. 68. 1539-1542).
• Enhance physical performance - most studies have shown no effect (Am Fam Physician. 2003. 68. 1539-1542). A review of 35 in vivo studies of ginseng in both animals and humans concluded that the quality of the research is too low to serve as convincing evidence of ginsengs efficacy in improving human physical performance (Sports Medicine. 2000. 29. 113-133).
• Enhance immune system function - several positive studies (Am Fam Physician. 2003. 68. 1539-1542).
• Erectile dysfunction
• Korean red ginseng 900 mg 3 times a day shown effective in an 8 week RCT with 45 patients with clinically diagnosed erectile dysfunction (J Urol. 2002. 168. 2070-2073).
• A systematic review of 7 RCTs (n=363) of Korean red ginseng root showed that ginseng root was superior to placebo. The methodologic quality of the trials was low and the number of subjects in the trials was small. Dosage ranged from 1800 - 3000 mg/day and duration of study ranged from 4-12 weeks (Br J Clin Pharmacol. 2008. 66. 444-450).
• Prevention of URI – all studies industry sponsored, examined a proprietary extract, CVT-E002 (Alt Med Alert. 2007. 10. 25-28).
• The initial study represented a combination of 2 RCTs, and showed minimal benefit (J Am Geriatr Soc. 2004. 52. 13-19).
• A 4 month RCT in which 279 subjects with a history of at least two upper respiratory infections in the previous year took either placebo or North American ginseng (Panax quinquefolius) 400 mg per day of an extract standardized to 80% poly-furanosyl-pyranosyl-saccharides and 10% protein, showed that those in the experimental group experienced fewer recurrent URIs and fewer total symptoms per URI (CMAJ. 2005. 173. 1043-1048).
• A small 4 month RCT in 43 volunteers found that subjects reported significantly fewer URI symptoms during the final 8 weeks of the study (J Altern Complement Med. 2006. 12. 153-157).
• Dosage - 100-200 mg daily of standardized extract with 7% ginsenosides (Panax) or 0.8% eleutherosides (Siberian), or 0.5- 1 gram of dried root 3 times a day.
• Quality
• A study done by the Philadelphia College of Pharmacy analyzed 54 ginseng products and showed that 60% of those analyzed had very little ginseng, with no ginseng at all in 25% (Whole Foods. 1979. 2. 48-53).
• Another study of ginseng products found tremendous variability, with as little as 12% and as much as 328% of the active ingredient in the bottle, compared to the information on the label (Am J Clin Nutr. 2001. 73. 1101-1106).
• Safety
• Siberian ginseng (Eleutherococcus senticosus) has no known side effects, but it can interfere with the digoxin assay and cause false elevation of digoxin levels.
• Panax ginseng interferes with platelet aggregation, but does not affect the pharmacokinetics or pharmacodynamics of coumadin (Br J Clin Pharmacol. 2004. 57. 592-599), and may cause nervousness, palpitations, high blood pressure, and sleeplessness through central nervous system stimulant activity.  It has also been reported to cause severe headache, diarrhea, vaginal bleeding, and Stevens-Johnson syndrome.  Many experts suggest cycling with 2-3 weeks taking ginseng, followed by 1-2 weeks off the herb.  Discontinue at least 7 days before surgery.
• American ginseng interacts with coumadin to lessen the effect of coumadin, slightly decreasing the INR, based on a RCT in 20 healthy subjects (Ann Intern Med. 2004. 141. 23-27).
• American (North American) ginseng does NOT significantly raise blood pressure based on data in a RCT in 52 people in which 24 hour ambulatory BP was measured after 12 weeks of consuming t his product. Limitations of this study a small sample size with a significant drop out rate (29%) and a 12 hour lag between the last ingestion of ginseng and initiation of the 24 hour ambulatory measurement (Hypertension. 2006. 47. 791-796).
• Korean ginseng does not affect INR, based on data from an open label, three-way, randomized crossover trial in 12 individuals (Br J Clin Pharmacol. 2004. 57. 592-599).
• Mechanism of action - stimulation of the central nervous system, modulation of the immune system, and anabolic effects, accelerating hepatic lipogenesis and increasing glycogen storage.
• Ginsana is the best studied brand name.
• Goldenseal
• Uses:
• Mouthwash for canker sores.
• Topical treatment for sore throats.
• Berberine, a compound in goldenseal with antibacterial and anti-yeast properties is available in supplement form
• Safety: Aquaretic (increases water excretion without increasing sodium excretion) and therefore may worsen edematous states or counteract effects of prescription diuretics.  May inhibit cytochrome P450 3A4.  Some herbalists recommend use for a maximum of 10 days.
• Research - no clinical trials (2004), but a growing body of basic research on the whole herb and also one of the key constituents, berberine.
• ENDANGERED SPECIES DUE TO OVER-HARVESTING.
• Myths:
• Effective for prevention or treatment of colds - it is not.
• Masks illegal or controlled substances in the urine - it does not.
• Dosage: 250-500 mg three times a day for intestinal infections.  Dose of tincture is 2-4 ml three times a day.  Dose of liquid extract is 0.3 to 1 ml three times a day.  To make a tea or a mouthwash, simmer 1 gram of dried root in 150 ml of water for 10 minutes, then strain.
• Grape seed extract - see pine bark extract below for details of the possible benefits and dose of the PCO's found in this herb.
• Gugulipid - return to Home Page and click on ‘Cholesterol’ for details on this herb.
• Gymnema sylvestre (Gumar) - may lower blood sugar in diabetics and may decrease craving for sugar.
• Hawthorn (Crataegus)
• Uses (some authorities say is must be used for 6-12 months before a benefit is seen)
• Congestive heart failure (CHF)
• In a European multi-center observational study of 1011 patients with New York Heart Association class II CHF, 24 weeks of treatment with a standardized formulation (WS 1442) 450 mg twice a day, clinical improvements were seen in exercise tolerance, fatigue, and dyspnea. Decreases in ankle edema and nocturia were also reported, as were improvements in blood pressure and ejection fraction (Herz. 1999. 24. 465-474).
• A systematic review of 8 RCT's (433 patients) of hawthorn in class II CHF showed improvements in subjective symptoms and exercise tolerance.  These trials were of variable methodological quality, mostly 8 weeks or less in duration (Fortschr Med. 1996. 114. 27-29).
• In a multi-center RCT of 209 patients with class III CHF for at least 6 months, and with a 4 week run-in phase combining placebo with diuretics, those treated with 1800 mg WS 1422 daily showed significantly increased maximal workload compared to both placebo and the group of 69 patients treated with 900 mg daily of WS 1422 (Am Heart J. 2002. 143. 910-915).
• A meta-analysis of 13 trials, 8 of which evaluated the effect on maximal work load, and 5 of which evaluated the effect on symptoms, found significant benefit with regard to both of the above endpoints; adverse effects were generally mild and transient (Am J Med. 2003. 114. 665-674).
• MIXED results trial – SPICE trial. This trial examined the effect of 450 mg twice a day of WS 1422 as an adjunct to conventional treatment on mortality in class II or III heart failure and EF < 35%. More than 2600 patients were randomized; enrollment started in 10/98. Results published in 2008 indicated that hawthorn may protect against cardiac death and sudden death, but there was no added symptomatic benefit with addition of hawthorn to conventional treatment (Eur J Heart Fail. 2008. 10. 1255-1263).
• NEGATIVE trial - HERB-CHF Trial, sponsored by NCCAM. This was a 6 month RCT which compared 450 mg twice a day of extract WS 1422 with placebo in 120 patients with mild to moderate CHF, and an EF<40%. There was no effect on 6 minute walk distance (Eur J Heart Failure. 2004. 6. 953-955). Retrospective secondary analysis of data from this trial showed that hawthorn does NOT reduce heart failure progression, and surprisingly may increase the risk for early heart failure progression (Eur J Heart Fail. 2008. 10. 587-593).
• A systematic review of 6 RCTs, a nonrandomized cohort study, and a prospective cohort study identified numerous beneficial effects of hawthorn (Eur J Heart Failure. 2008. 10. 1153-1157).
• A Cochrane review of 14 RCTs concluded “there is significant benefit in symptom control and physiologic outcomes from hawthorn extract as an adjunctive treatment for chronic heart failure” (Cochrane Database Syst Rev. 2008. CD005312).
• HTN – slight BP (~2-6 mm Hg) lowering noted in several clinical trials (Phytother Res. 2002. 16. 48-55; Drugs Exp Clin Res. 2004. 30. 221-225; Br J Gen Pract. 2006. 56. 437-443). Review article (Alt Med Alert. 2008. 11. 1-4).
• May also be useful in Raynaud's and coronary artery disease.
• Dosage is 4-5 ml three times a day of tincture (1:5), 1-2 ml three times a day of fluid extract (1:1), or 300-900 mg twice a day of standardized extract of the leaf and flower of the plant.
• Mechanism of action - antioxidant, anti-inflammatory, positive inotropic effects, beta blocking effects, vasodilator.
• Safety
• Very safe; adverse effects reported in only 1.3% of 3664 patients participating in a post marketing analysis evaluating daily treatment with 900 mg of extract (Am J Med. 2003. 114. 665-674)
• Side effects may include and dizziness and vertigo (most common), GI upset, rash, headache, diaphoresis, palpitations, insomnia.
• Theoretically may potentiate the action of digoxin, based on its effects on p-glycoprotein. HOWEVER, lack of interaction in a pharmacokinetic trial in 8 healthy volunteers (J Clin Pharmaacol. 2003. 43. 637-642).
• HeartCare is the best studied brand name. RCTs included in the Cochrane review used either standardized extract WS 1442 (standardized to or 18.75% oligomeric procyanidins) or LI 132 (standardized to 2.2% flavonoids).
• Hops flower extract - anxiety, insomnia, approved by The German Commission E.
• Horse chestnut seed extract - chronic venous insufficiency, 300 mg capsules twice a day, standardized to 18-27% ascein.
• In a 12 week RCT with 240 patients, 50 mg ascein twice a day was as effective as compression stockings (Lancet. 1996. 347. 292-294).
• A Cochrane review identified 17 trials (n=1581) which met inclusion criteria. Of these, 12 were placebo controlled, 4 were controlled against O-beta-hydroxyethyl rutoside, 2 were controlled against compression stockings, and 1 was controlled against pycnogonel. Heterogeneity precluded meta-analysis.  In aggregate, the trials showed significant reduction in leg edema (Cochrane Database Syst Rev. 2006. CD003230). A commentary indicates that only short durations of treatment were studied and that GI upset and dizziness were fairly common side effects (ACP Journal Club. 2006. 145. 20).
• Side effects in clinical trials include dizziness, nausea, headache, and pruritis.  May interact with coumadin and prolong INR.
• Venastat is the best studied brand name.
• Jewelweed - excellent substitute for steroids for treatment of poison ivy dermatitis (Annals of Allergy. 1958. 16. 526-527).
• Juniper – aquaritic/antiseptic herb which is potentially toxic as per Varro Tyler (Herbs of Choice. 1994) because the oil contains terpene hydrocarbons which can cause kidney damage.
• Kava-Kava (Alt Med Alert. 2007. 10. 49-55)
• Uses - Treatment of anxiety, including perimenopausal anxiety. May also be useful for treatment of insomnia.
• A systematic review of 7 RCT's including a total of 377 patients found that most of these were of good quality, 4 with a Jadad score of 5/5.  The 4 studies which could not be combined in a meta-analysis along with the 3 studies meta-analyzed (all 3 studies used kava extract WS 1490 100 mg three times a day) all showed a greater reduction in anxiety for kava extract than for placebo.  Measurement of efficacy was based on scores on the Hamilton Rating Scale for Anxiety.  (J Clin Psychopharmacol. 2000. 20. 84-89). 
• A Cochrane review of 7 RCT's also concludes that kava shows superiority over placebo (Cochrane Database Syst Rev. 2002. CD003383). 
• An update of the Cochrane review included 11 trials and 645 participants (Cochrane Database Syst Rev. 2003. CD003383). 
• An 8 week RCT in 129 outpatients comparing kava 400 mg of L1 150 with buspirone 10 mg with opipramol 100 mg found kava as effective as the pharmaceutical agents (Phytomedicine. 2003. 10[suppl 4]. 38-49).
• A RCT in 40 patients showed that kava allowed for dosage tapering of benzodiazepines without loss of anti-anxiety effect (Psychopharmacology. 2001. 157. 277-283).
• A 3 week crossover RCT in Australian patients, using an aqueous extract from the roots of noble cultivars at a standardized dose 250 mg kavalactones per day, showed both safety and efficacy (Psychopharmacology. 2009. 205. 399-407).
• Negative trials – 3 small RCT’s failed to show benefit (Int Clin Psycopharmacol. 2006. 21. 249-253), but these were 4-8 weeks in duration, and onset of beneficial effect may not occur for 8 weeks
• Dosage - 70-240 mg 3 times a day of  a standardized extract containing 30%-70% kavalactones or 1 dropperful of a standardized liquid extract 3 times a day.  Most controlled trials used a dose of 100 mg three times a day of a preparation with 70% kavalactones. For sedation, suggested dose is 180-210 mg of kava lactones 1 hour before bedtime.  Good quality liquid extract should numb the tongue.
• Mechanism of action - Uncertain, but may enhance binding of the neurotransmitter GABA to its receptor in the amygdala, without acting as a direct agonist. Kavapyrones also have a central muscle-relaxing action and anticonvulsant actions.
• Safety
• Long history (at least 1500 years) of traditional use (of a water extract) by indigenous populations in the South Pacific Islands, with no apparent safety concerns.
• Safety good in controlled trials - a systematic review of 7 RCTs including a total of 377 patients did not identify any safety issues (J Clin Psychopharmacol. 2000. 20. 84-89).
• In 2001, the German Federal Drug Agency announced 24 cases of liver toxicity and one death.
• There were published case reports of hepatotoxicity and hepatic failure (BMJ. 2001. 322. 139; Ann Intern Med. 2001. 135. 68-69). 
• Kava was banned in several European countries
• In the U.S. the FDA released a Consumer Advisory 3/25/02. The FDA advisory recommends suggest limiting the daily dose to 300 mg of total kavalactones and limiting daily use to a 4 week period.
• In Australia, the TGA (Therapeutic Goods Administration) issued a Fact Sheet in April of 2005 (updated 9/20/10) which recommended a limit of 125 mg kavalactones per tablet or capsule, and a limit of 250 mg of kavalactones per day.
• With regard to the case reports of hepatotoxicity, the British Medicines Control Agency concluded after careful review that in 12 of the 27 case reports, kava as the cause was either unlikely or inaccessible.  In 12 of the remaining 15 case reports, the individuals were taking conventional medication with hepatotoxic potential along with kava.  In two of the remaining 3 case reports, there was high alcohol consumption in association with kava ingestion. Nonetheless, in these initial 27 case reports of hepatotoxicity, there were six positive dechallenges and two positive rechallenges.
• In the United States, close inspection in 2001 of adverse event reports on file with the FDA showed that many of them were in association with a single instance of an adulterated product which actually contained no kava distributed at a New Year’s Eve rave in Los Angeles. An article in the New York Times 1/16/02 erroneously cited 60 kava-related adverse event reports by including the 29 “fX” cases in which there was actually no kava in the product distributed at the rave.
• Subsequent analysis of the German report concluded that the death was due to alcoholic liver failure and not kava, that 4 of the 24 cases were listed twice, that 3 of the 24 cases had no connection to kava, that in 11 of the 24 cases other medications were involved, and that 10 other cases had uncertain connections to kava. Three of the 24 cases did appear related to kava, and 2 of the 3 appeared related to overdoses, leaving only one case in which kava monotherapy at recommended doses was associated with hepatotoxicity (Phytomedicine. 2003. 10. 440-446).
• Subsequent investigation by the World Health Organization confirmed a (rare) risk of hepatotoxicity with kava consumption (WHO Document Production Services. 2007).
• A clinical review confirmed the association of kava ingestion with hepatotoxicity on rare occasions – this review incorporated structured, quantitative, liver-specific causality assessment (Ann Hepatol. 2010. 9. 251-265).
• Initially, as reports of toxicity surfaced in the early 2000’s, Swiss researchers linked the toxicity to an acetone-extraction manufacturing process which is widely used in German and Swiss products, and creates a highly concentrated final product. However, subsequent data shows that liver injury has been caused in some cases by the traditional water-based kava extracts (WHO Document Production Services. 2007; Liver Int. 2010. 30. 1270-1279). There is electron microscopy data suggesting that kavain has an adverse effect on hepatocytes (World J Gastroenterol. 2008. 14. 541-546). Preliminary data suggests that flavokavain B might be responsible for hepatotoxicity (Zhou P et al. FASEB J. epub 8/9/10). Nonetheless, the use of ethanol or acetone as solvents, as compared to a water extract, might increase the risk of hepatotoxicity.
• Traditional use of kava involves an extract prepared from the peeled rhizome – some of the cases of hepatotoxicity might have arisen from use of aerial parts of the plant, as stems and leaves might contain a toxin, pipermethysticin (Phytochemistry. 2003. 63. 193-198).
• Further investigation into kava hepatotoxicity revealed the existence of more than 200 varieties of this herb, referred to as cultivars. Traditional use involves consumption of kava from a group of 28 cultivars known as ‘noble,’ with Borugu as one of the preferred noble cultivars for traditional use.
• Case reports of overdoses of kava not associated with hepatotoxicity suggest that hepatotoxicity is an idiosyncratic reaction and not a dose-dependent direct toxicity. A polymorphism of cytochrome P450 2D6, not detected in Pacific Islanders, but with a 10% prevalence in Europeans may cause poor detoxification of kavalactone metabolites, and thus accumulation (Ann Intern Med. 2001. 135. 68-69).
• CONCLUDE in 2010 that safety is maximized by using only a water-based extract derived from peeled rhizomes of a noble cultivar such as Borogu, and at a maximum dose of 250 mg kavalactones per day.
• Historically, based on an estimate of 250 million daily doses of ethanolic kava extract consumed in the previous decade, with only 2 causal cases of hepatotoxicity, one report quoted an incidence rate of 0.008 adverse effects per million doses of kava compared with 2.12 per million doses of diazepam (Duetsche Apotheker-Zeitung. 2002. 142. 58-63). 
• Side effects include excessive sedation (especially if taken with benzodiazepines or alcohol), stomach complaints, restlessness, headache, and tremor. 
• Long term use occasionally associated with a skin reaction similar to psoriasis (J Am Acad Dermatol. 1994. 31. 89-97).
• Licorice
• Uses: Peptic ulcer disease, aphthous ulcers, inflammation, plaque reduction in the mouth.
• In a 4 week double blind study of 50 patients with duodenal ulcer and 6 patients with gastric ulcer, DGL demonstrated efficacy using symptoms and radiographic healing as endpoints.  Both groups received two tablets three times a day after meals.  The tablets in the experimental group (Caved-S) consisted of DGL 380 mg, bismuth subnitrate 100 mg, aluminum hydroxide gel 100 mg, magnesii carbonas levis 200 mg, sodium bicarbonate 100 mg, and powdered frangula bark 30 mg (Gut. 1968. 9 48-51). Positive results were also found in a one month double blind trial in 33 patients with gastric ulcer, using the same active treatment and using radiographic endpoints (Gut. 1969. 10. 299-302).  However, in another 30 day double blind trial in 47 patients with active duodenal ulcer using the same dose of the same active treatment above, results were negative (Gut. 1971. 12. 449-451).
• In a study in 100 patients with gastric ulcers, DGL 760 mg three times a day was as effective as prescription Tagamet 200 mg 3 times a day  or 400 mg at bedtime, after 6 and 12 weeks of treatment.  In another study in 874 patients with chronic duodenal ulcers, DGL compared favorably with Tagamet, with 90% healing in both groups at 12 weeks.  The relapse rate with DGL was significantly lower, 8.2% versus 12.9% with Tagamet (cited in Hospital Practice. 8/15/01. 55-59).
• However there are several negative placebo-controlled RCT's too.  These include a 4 week trial in 96 patients with gastric ulcer (Gut. 1978. 19. 779-782), an 8 week trial in 34 patients with active duodenal ulcers (BMJ. 1977. 2. 1123), and a 6 week multicenter trial in 90 men with relapse of chronic duodenal ulcer who received 760 mg DGL three times a day (BMJ. 1971. 3. 501-503).
• Conclude data inconclusive.
• Safety: Inhibits hepatic cytochrome P450 3A4, so multiple herb-drug interactions are possible.  Prolonged use can cause pseudohyperaldosterism; use in conjunction with thiazide diuretics can cause marked hypokalemia.  Avoid these problems with DGL (deglycyrrhizinated licorice).
• Dosage: 5-15 grams of licorice, containing 200-600 mg glycyrrhizin a day for up to 6 weeks, or 2-4 250-380 mg chewable tablets of DGL 30 minutes before meals.
• Life root - unsafe secondary to pyrrolizidine alkaloids (J Am Pharm Assoc. 1996. 36. 29).
• Milk Thistle
• Uses: acute and chronic viral hepatitis, alcoholic liver disease, cytoprotection, anticarcinogen, Amanita phalloides poisoning (used intravenously in Germany).An evidence report/technology assessment from the Agency for Healthcare Research and Quality published 12/4/00 identified 16 prospective studies evaluating milk thistle in liver disease, 14 of which were placebo controlled, and concluded that the current evidence is inadequate for consideration as evidence in favor of milk thistle.  Despite this conclusion, some data are suggestive, according to a review article (Am J Gastroenterol.  1998. 93. 139-143). Another review article reports in the abstract that “Clinical studies are largely heterogeneous and contradictory” (Am Fam Physician. 2005. 72. 1285-1288).
• Mechanism of action – silymarin has ability to raise intrahepatic glutathione levels.
• Dosage: 200-400 mg/day of silymarin; use a standardized extract with 70% - 90% silymarin.
• Safety: generally well tolerated; may significantly lower blood sugar in diabetics with alcoholic cirrhosis. In 2005, Vital Nutrients found that all brands tested had solvent residue (this company switched to using a crude extract rather than a standardized extract contaminated with residual solvent).
• Cost: $15 – $30/month.
• Thisylin is the best studied brand name. Ultrathistle is a seed extract bound to phosphatidylcholine, and is much more expensive.
• Mistletoe
• Uses: possible anti cancer effects if administered by injection. Very popular in Europe, and usually injected subcutaneously. Mistletoe is used primarily as adjunctive therapy.
• Data on the effectiveness of mistletoe is mixed, with clinical studies failing to “produce convincing data that mistletoe extract can positively affect relevant endpoints” (Alt Med Alert. 2005. 8. 55-59).
• A systematic review found that several prospective studies have reported benefits; the highest quality evidence supports beneficial effects on quality of life and reduction of side effects of cytotoxic cancer treatments (Eur J Med Res. 2007. 12. 103-119).
• Cancers which seem to respond include colon, rectum, stomach, breast, and lung (Altern Ther Health Med. 2001. 7. 57-66, 68-72, 74-78).
• A RCT of 477 patients with squamous cell cancer of the head and neck who received standard treatment alone or standard treatment plus mistletoe found no significant added benefit of mistletoe at 4 year follow up (Eur J Cancer. 2001. 37. 23-31).
• Mechanism of action – immunomodulation mediated by lectins; cytotoxicity mediated by viscotoxins. 
• Dosage – individualized, with doses given 3-7 times per week over weeks to months.
• Iscador is the oldest product of mistletoe. 
• Iscar, which is a brand name of Iscador, has been listed since 1999 with the U.S. FDA in accordance with the requirements for homeopathic medicines.
• Since the 2002 Bioterrorism Act, the FDA disallowed importation or distribution of injectable mistletoe extracts, including homeopathic formulations, so it is only the oral form that is available commercially in the U.S.
• Mullein - chest congestion and dry bronchial coughs.    Dosage is 3-4 teaspoonfuls containing 1.5-2 grams in a tea.
• Passionflower - tranquilizer.  Dosage is 3-6 teaspoonfuls containing 4-8 grams/day in a tea.  A RCT of 36 patients with generalized anxiety of greater than 6 months duration, with a HAM-A score of greater than 14 showed that those given 45 drops per day of a commercial Passionflower extract (Passipay) for 28 days showed as much improvement as those given oxazepam 30 mg per day, with significantly less impairment of job performance (J Clin Pharm Ther. 2001. 26. 363-367). Approved monograph in The Commission E.
• Pelargonium sidoides (Alternative Medicine Alert. 2005. 8. 8-11; Alternative Medicine Alert. 2007. 10. 43-45)

o Plant is native to coastal regions of South Africa; an extract of the root is used therapeutically for URI’s.

• In a RCT in 143 children aged 6-10, all of whom had a negative rapid strep screen and a tonsillopharyngitis severity score > 8 points, 20 drops tid for 6 days of EPs 7630 was beneficial. The decrease in the severity score at day 4 was 7.1 points in the treatment group and 2.5 points in the control group.  Duration of illness was 2 days shorter in the treatment group (Altern Ther Health Med. 2003. 9. 68-78).

o In a RCT in 468 adults with acute bronchitis of less than two days duration and a BSS > 5, those who received 30 drops (1.5 ml) 3 times a day of EPs 7630 30 minutes before or after a meal had a significantly greater decrease in the BSS score (p<0.0001) and were able to return to work two days sooner (p<0.0001). Adverse events were comparable to placebo (Phytomedicine. 2003. 10. Suppl 4. 7-17).

o In another RCT in 124 adults with acute bronchitis with symptoms > 48 hours and a BSS > 5, benefit was seen in the group that received 30 drops (1.5 ml) 3 times a day of EPs 7630. Adverse events were comparable to placebo (Explore. 2005. 1. 437-455).

o Beneficial in the common cold (i.e. viral URI) based on data from 9 randomized trials conducted on a total of 1477 patients, including 680 children ages 6-12.

o In a multicenter RCT in 103 adults with the common cold, 30 drops 3 times a day of EPs 7630 reduced the severity of symptoms and shortened the duration of illness. Entry criteria were at least two major and one minor cold symptoms, or one major and 3 minor cold symptoms (maximum CIS symptom score of 40 points), for 24-48 hours. After 10 days, 78.8% of the treatment group versus 31.4% of the placebo group were clinically cured (p<0.0001). The mean duration of inability to work was 6.9 days in the treatment group versus 8.2 days in the placebo group (p=0.0003) [Explore. 2007. 3. 573-584].

o Open-label observational studies in more than 2500 adults and children found adverse effects in 1.2-15.5% - effects largely mild and generally GI or skin related.

o Contra-indicated in pregnancy and lactation, based on lack of data.

o Dose of the extract is 20 drops (1 ml) tid in children and 30 drops (1.5 ml) 3-5 times per day in adults.

o Brand names include EPs 7630, an ethanolic root extract manufactured by Dr. Willmar Schwabe Pharmaceuticals in Germany, and Umcka ColdCare, a homeopathic 1X preparation, available in the U.S. from Nature’s Way.

• Pennyroyal - may be hazardous.  Reports of liver damage, kidney damage, and death.
• Peppermint - digestive problems, menstrual cramps. (Contraindicated in GERD). Mechanism of action - spasmolytic.  In a small double-blind 3 week crossover trial, enteric coated peppermint capsules with 0.2 ml of oil, 1-2 capsules TID, were associated with significant relief of abdominal symptoms (p<0.005). [BMJ. 1979. 2. 835-836]. A meta-analysis of 8 randomized, controlled trials indicates that peppermint oil could be effective for symptom relief in irritable bowel syndrome (Am J Gastroenterol. 1998. 1131-1135).
• Pine bark extract (Pycnogenol) - potent anti-oxidant, but expensive. Active ingredient, referred to as OPC's, by chemical analysis have antioxidant activity 50 times greater than vitamin C or E.   May be useful for general health and also for treatment of venous insufficiency, capillary fragility, diabetic retinopathy, macular degeneration.  In an open, controlled 4 week comparative study in 40 patients with chronic venous insufficiency, Pycnogenol 360 mg per day was found to be more efficacious than horse chestnut seed extract 600 mg per day, with regard to both subjective scores and measurement of leg circumference.  Pycnogenol also significantly reduced cholesterol and LDL cholesterol levels (Phytotherapy Research. 2002. 16. S1-S5).  Dose is 50 mg per day for prevention or 150-300 mg per day for treatment.  Grape seed extract is less expensive than pine bark extract, and contains 92% to 95% OPC's compared to 80% to 85% in pine bark extract.
• Pokeroot – unsafe (J Am Pharm Assoc. 1996. 36. 29).
• Psyllium - bulk laxative (Aliment Pharmacol Ther. 1995. 9. 639-647), and also lowers cholesterol.  In one study 15 cc (one tablespoon) twice a day lowered cholesterol 15% and LDL cholesterol 20% in adults on a Step I American Heart Association Diet (Arch Intern Med. 1988. 148. 292-296).   A meta-analysis of 5 studies using a total of 10.2 grams per day of psyllium seed husk as an adjunct to Step I AHA diet found that psyllium was associated with significant reductions in total cholesterol and LDL cholesterol (Am J Clin Nutr. 2000. 71. 472-479).
• Pygeum africanum
• Benign prostate hypertrophy.  
• A literature search found 18 randomized trials of 1562 men. A meta-analysis of six of these studies which were placebo controlled and in which diagnosis was confirmed and treatment lasted at least 30 days found that nocturia was reduced by 19% and peak flow increased 23% and residual volume fell 24% in the treatment group.  Adverse effects were mild and generally comparable to placebo (Am J Med. 2000. 109. 654-664). 
• A Cochrane Review of the 18 RCT's which compared the herbal extract to placebo found limited evidence that the extract is more effective than placebo for improving symptoms and urodynamics.  Problems cited with the individual studies included small size, short duration (mean of 64 days, range of 30-122 days), varied doses and preparations, and lack of use of standardized validated measures of efficacy (Cochrane Database Sys Rev. 2002. CD001044).  
• Dose is 100-200 mg per day of a standardized extract (12-13% phytosterols).
• Red clover
• May decrease hot flashes in menopausal women – Return to Home Page and click on Menopause outline for detailed information
• Traditional uses include bronchitis, childhood eczema, pharyngeal inflammation, psoriasis, whooping cough, and as a component of the Hoxsey anti-cancer formula.
• Sassafras – unsafe (J Am Pharm Assoc. 1996. 36. 29) and has no significant therapeutic utility as per Varro Tyler.
• Saw palmetto (partially dried, ripe fruit of Serenoa repens)
• Uses: BPH, may also enhance sperm production, increase breast size, and may be beneficial in treatment of hair loss, polycystic ovary disease, acne, and asthma.
• A 2009 Cochrane review of 30 trials concluded that saw palmetto has little or no efficacy over placebo for treating BPH symptoms, although it appears to be safe (Cochrane Database Syst Rev. 2009. CD001423). This was a change from the conclusions of 2 earlier Cochrane reviews.
• A 2001 review of 10 placebo controlled studies of monopreparations, 3 studies of combinations of saw palmetto and other herbal products, 2 studies which compared saw palmetto with finasteride, and 1study which compared saw palmetto with another herbal product concluded that saw palmetto was efficacious (Cochrane Database Syst Rev. 2001. CD001423). 
• An update which included 3 new trials with 230 additional men (total of 3139 men and 21 RCTs lasting 4-48 weeks) came to similar conclusions (Cochrane Database Syst Rev. 2002. CD001423).
• A multicenter RCT of 369 men aged 45 or older, conducted at 11 North American clinical sites, in which saw palmetto was dosed at 320 mg a day for 24 weeks, then 640 mg a day for 24 weeks, then 960 mg a day for the final 24 weeks of this 72 week study found no benefit with regard to lower urinary tract symptoms (JAMA. 2011. 306. 1344-1351).
• A methodologically rigorous one year RCT of 225 men over age 49 with moderate to severe symptoms of BPH found no benefit to a saw palmetto extract 160 mg twice a day. Side effects in the saw palmetto group were similar to those in the placebo group, and there was no significant change in PSA, but there was no significant improvement in symptom scores (AUASI), maximal urinary flow rate, prostate size, residual volume after voiding, or quality of life. The lead investigator of this trial commented that finding a true placebo control such that participants could not differentiate the active herb from the placebo by smell and taste was a challenge successfully met in this study, and lack of successful blinding may be a reason that previous trials were positive. This trial differed from many other trials though in that the men enrolled had moderate to severe BPH at baseline, with AUASI baseline scores of 8-35. This study was funded by the NIH and the saw palmetto was provided by Rexall-Sundown (N Engl J Med. 2006. 354. 557-566 and editorial 632-634).
• Historically, a systematic review that included 18 randomized trials with 2939 men found that saw palmetto improved symptoms of BPH.  Improvement in symptoms and urinary flow measures was similar to that produced with the prescription medication finasteride (Proscar). Most of these trials were conducted in men with mild to moderate BPH symptoms (stages 1 and 2). The reviewers did note that some of the studies included in the review were flawed (JAMA. 1998. 280. 1604-1609). 
• Dosage - Standardized liposterolic extract, 80-160 mg twice a day, standardized to contain 85% to 95% fatty acids and 0.2% to 0.4% sterols.  Allow at least 2-3 months before judging whether or not it is beneficial.
• Mechanism of action - inhibits 5-alpha reductase activity (similar to Proscar in this regard), inhibits DHT binding to cellular and nuclear receptors, inhibits cyclooxygenase and 5-lipoxygenase and has spasmolytic activity.
• In one study of 6 months duration, did not affect the PSA level (Urology. 1998. 51. 1003-1007). 
• Main active constituents are fatty acids and sterols.
• Safety - Adverse effects are rare and usually mild, and may include gastrointestinal upset, diarrhea, constipation, urine retention, headache, and decreased libido.  In studies comparing with finasteride (Proscar), side effect profile better for saw palmetto (Prostate. 1996. 29. 231-240 and Urology. 1998. 51. 1003-1007).
• Quality - Quanterra and ProstActive are the best studied brand names.  In 2000, Consumer Lab reported that 17 of 21 leading brands passed the test of quality, containing at least 85% fatty acids.
• Schizandra - touted for treatment of liver conditions, but safety and efficacy unproven as per Varro Tyler.
• Senna - stimulant laxative, but it can cause cramping and intestinal discomfort, and long term use can create bowel dependency and dangerous electrolyte imbalances, so use with caution.
• Skullcap (Scutellaria lateriflora) - the reports of hepatoxicity (listed in Consumer Reports 5/04 ‘Dirty Dozen’) appear to be associated with products adulterated with germander (Teucrium chamaedrys) [Botanical Safety Handbook. 1997; Pharmaceut J. 1984. 233. 80-82; Ann Intern Med. 1992. 117. 165-166].
• Slippery elm - sore throats.  Declared safe and effective by the FDA, as per Varro Tyler.
• St. John's wort
• Uses: depression; might be useful in treatment of back pain, burns and in general for wound healing.
• A meta-analysis of 23 randomized studies, none published in English, including a total 1757 patients, also showed efficacy for St. John's wort, with St. John's wort more efficacious than placebo in 17 of the 23 original studies, and equal in efficacy to prescription antidepressants in the other 6 original studies (BMJ. 1996. 313. 253-258).
• A number of other reviews and meta-analyses have been reported, all of them finding efficacy for St John's wort in treatment of mild to moderate depression (Eur Neuropsychopharmacol. 1999. 9 501-505; Arch Intern Med. 2000. 160. 152-156; J Nerv Ment Dis. 1999. 187. 532-538; Ann Intern Med. 2000. 132. 743-756). 
• A meta-analysis of 27 RCT's with an average Jadad score for quality which was "good" found that the 17 trials which were placebo controlled showed efficacy of St. John's wort in mild to moderate depression, and the 10 trials which compared St. John's wort to prescription medications showed apparent equivalence to maprotiline, imipramine, bromazepam, amitriptyline, and diazepam (Cochrane Database Syst Rev. 2000. CD000448). 
• Furthermore, a rigorous three-armed RCT not included in any of the above reviews in which 263 patients with moderate depression received either St. John's wort extract 1050 mg/day, imipramine/day, or placebo for 8 weeks found St. John's wort more efficacious than placebo and equal in efficacy to imipramine.  The placebo response rate in this trial was 63%, which suggests that the results may not be generalizable (BMJ. 1999. 319. 1534-1538). 
• Furthermore, a large European 6 week RCT found St. John’s wort (WS 5570 300 mg tid) more effective than placebo at reducing HAM-D scores in outpatients with mild to moderate depression (Am J Psychiatry. 2002. 159. 1361-1366).
• However, an 8 week NIH-sponsored RCT in 200 outpatients at 11 U.S. academic medical centers with severe major depression (baseline HAM-D score of at least 20) concluded that St. John’s wort (Jarson 300 mg tid) was not any more effective than placebo.  The primary outcome measure was the rate of change on the HAM-D over the treatment period.  Headache was the only adverse effect which occurred more frequently in the active treatment group than placebo. This trial included a 1 week single blinded run-in of placebo. With regard to a secondary outcome measure, St. John’s wort did produce a significantly greater remission rate than placebo in this study (14.35% vs. 4.9%). The subjects in this trial had chronic depression, with average duration of symptoms prior to the trial of two years (JAMA. 2001. 285. 1978-1986). Even though there was no active control in this RCT, a non-blinded extension of this trial found that non-responders to St. John’s wort in this study who were subsequently treated with a prescription antidepressant of the investigator’s choice for 24 weeks did respond to treatment (J Clin Psychiat. 2004. 65. 1114-1119).
• Furthermore, another 8 week RCT in 340 adult outpatients at 12 different centers with severe major depression, with baseline HAM-D scores of at least 20 which compared St John's wort (LI160 300 mg tid, titrated up to 1500 mg/day) to both placebo and Zoloft (50-100 mg/day) found that neither the St John's wort nor Zoloft outperformed placebo in terms of either primary outcome measurement, improvement in HAM-D or improvement in CGI-I (clinical global impression scale).  The overall response rate (including partial and full response) in this study was 38.1% for St John's wort, 43.1% for placebo, and 48.6% for Zoloft.  Full responses were seen in 32% of placebo treated patients, 25% of Zoloft treated patients, and 24% of St John's wort treated patients.  While critics of St John's wort have cited this as another study showing the lack of efficacy of St John's wort, this is not a valid conclusion from this study when the Zoloft also did not outperform placebo. This study was sponsored by Pfizer, the manufacturer of Zoloft, and conducted at Duke University. Note that the media coverage of this trial which reported inaccurately that this trial showed St John’s wort ineffective was based on a press release which in hindsight was not balanced (JAMA. 2002. 287. 1807-1814).
• A 6 week RCT in 140 patients with moderate depressive disorder found that hypericum extract STW 3-VI 900 mg once/day was effective (Adv Ther. 2004. 21. 265-265).
• A 6 week RCT in 251 patients with moderate to severe acute major depression found that hypericum extract WS5570 was not inferior to paroxetine (Paxil). This study used hypericum extract WS 5570 initially 300 mg tid or Paxil 20 mg daily, with the dose in nonresponders increased at 2 weeks to 600 mg tid or 40 mg daily. Patients with symptoms for greater than one year were appropriately excluded from this study because of data that chronic major depression responds better to the combination of psychotherapy and pharmacotherapy. An editorial indicates that this was a methodologically sophisticated study which addressed weaknesses in previous studies (BMJ USA. 2005. 5. 154-155). A weakness of this study is that 3 of the authors had ties to the manufacturer of the St. John’s wort (BMJ. 2005. 330. 503-506).
• A 12 week RCT in 241 patients with moderate depressive disorder who received either St John’s wort 612 mg/day or sertraline 50 mg/day showed equal efficacy (Pharmacopsychiatry. 2005. 38. 78-86).
• A 6 week RCT in 163 adult outpatients with major depression found neither St. John’s wort (LI 160 300 mg tid) nor Prozac (20 mg daily) was superior to placebo in terms of the primary outcome measures of change in HAM-D from baseline to week 4 and week 6, but both the herb and the prescription medication improved remission rates compared to placebo (Eur Arch Psychiatry Clin Neurosci. 2005. 255. 40-47).
• A 12 week RCT in 135 patients with major depression found that extract LI 160 at a dose of 900 mg/day was more effective than fluoxetine 20 mg/day but not more effective than placebo (J Clin Psychopharmacol. 2005. 25. 441-447).
• A more recent meta-analysis of RCT’s, which included 37 trials, including 26 comparisons with placebo (n = 3320 patients) and 14 comparisons with prescription antidepressants (n = 2283 patients) concludes that “current evidence…is inconsistent and confusing” (Br J Psychiatry. 2005. 186. 99-107). Note that this sophisticated meta-analysis excluded 30 trials, including 7 trials that had been included in previous published reviews by the same group of authors. In the 6 trials comparing St John’s wort to SSRIs in those with major depression, there was no difference in response rates, but in the 12 trials comparing St John’s wort to placebo in those with major depression, the herb was only slightly more effective than placebo. In contrast, trials not restricted to major depression showed marked benefits for St John’s wort.
• A multicenter 3-arm RCT in 388 patients suffering from moderate depression found that 900 mg/day of hypericum extract was superior to placebo and similar in efficacy to citalopram 20 mg/day, with better safety and tolerability than citalopram (Pharmacopsychiatry. 2006. 39. 55-75).
• A RCT in 332 patients with mild to moderate major depression found that both 600 mg/day and 600 mg twice a day of extract WS 5570 were safe and more effective than placebo (BMC Med. 2006. 23. 14).
• A Cochrane review of St John’s wort for major depression examined 29 studies and almost 5500 adults and concluded that "…the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants" (Cochrane Database Syst Rev. 2008 (4): CD000448).
• A systematic review found that St John’s wort was more effective than placebo and as effective as standard therapy with better tolerability (Linde K. Forsch Komplementmed. 2009. 16. 146-155).
• Dosage -   300 mg three times a day of an extract standardized to contain either 0.3% hypericin or 1% - 6% hyperforin, or 1-1.5 ml of tincture three times a day.
• Mechanism of action - unclear, but thought to be related to selective inhibition of reuptake of serotonin, dopamine, and norepinephrine in the central nervous system. The active component is probably hyperforin and not hypericin.
• Safety
• Overall safety profile is excellent, with the herb tolerated as well as placebo in controlled trials. 
• May cause photosensitivity, headache, gastrointestinal upset – observational trials suggest adverse effects occur in only 1-3% of individuals. 
• However, it induces cytochrome P450 3A4, after as little as a 14 day course, (JAMA. 2003. 290. 1500-1504), and also induces P-glycoprotein, and therefore may increase the elimination of and thus decrease the effectiveness of 50% of all marketed medications, including amitriptyline, benzodiazepines, beta-blockers, calcium channel blockers, cyclosporine, digoxin, macrolide antibiotics such as erythromycin, oral contraceptives (birth control pills), protease inhibitors for HIV such as indivir, statins such as Lipitor, and theophylline. 
• The clinical relevance of many of the St. John’s wort – drug interactions remains unclear.
• No clinical signs despite 25-50% decreased serum levels of benzodiazepines (Int J Clin Pharmacol Ther. 2004. 42. 139-148).
• No clinical signs in a study of 12 patients, despite decreased amitryptiline levels (Int J Clin Pharmacol Ther. 2004. 42. 139-148).
• While there are case reports of unwanted pregnancies in women taking St John’s wort and oral contraceptive, a small RCT in 18 healthy females on low dose oral contraceptive found “no evidence of ovulation during low-dose oral contraceptive and St John's wort extract combination therapy” (Br J Clin Pharmacol. 2003. 56. 683-90).
• May increase the toxicity of antidepressants such as Serzone or Paxil (See Medical Letter 6/26/00 for numerous references regarding drug interactions).  Cytochrome P450 2C9 may also be induced.
• There are case reports of reduction in anticoagulant effect of coumadin, and data from one clinical trial that shows reductions in INR (Br J Clin Pharmacol. 2004. 57. 592-599). 
• Discontinue at least 5 days before any surgery.
• Quality control is a problem - a study subjecting 8 randomly sampled commercial products using HPLC to simultaneously measure hypericin and hyperforin found that the claim on the label regarding hypericin content did not correlate well with the measured content, and 6 of the 8 had a subtherapeutic hyperforin content (Am J Health Syst Pharm. 2002. 59. 545-547).
• The best studied brand names include Quanterra, Kira, Perika, and Movana.
• Stinging nettle
• Root relieves urethral and bladder irritation at a dose of 4-6 grams/day – approved by German Commission E.
• Leaves (freeze-dried extract) effective in allergic rhinitis (randomized, double blind study of freeze-dried preparation (Planta Med. 1990. 56. 44-47).
• Tea tree oil
• Uses: Onychomycosis (fungal infection of the fingernail or toenail), acne.
• A multicenter, RCT in 117 patients with culture proven subungal onychomycosis in which the control group applied 1% clotrimazole solution twice a day for 6 months reported that at the end of treatment the two groups were comparable, with culture evidence of a cure in 18% of the tea tree oil group and 11% of the clotrimazole group.  Partial or complete clinical remission was seen in 60% of the tea tree oil group and 61% of the clotrimazole group (J Fam Pract. 1994. 38. 601).
• In a single blind randomized trial in 124 patients with mild to moderate acne, 5% benzoyl peroxide was more effective in healing the inflamed lesions and faster acting than the 5% tea tree oil, but only 44% of the tea tree oil patients experienced side effects compared to 79% of the benzoyl peroxide patients (cited in Hospital Practice. 7/15/01. 57-60, cited on www.mothernature.com).
• Dose: For onychomycosis, apply 100% oil topically twice a day, for acne 5% to 15% oil topically four times a day.
• Safety: May cause tissue damage if used on burns or lacerations, so contra-indicated in these situations.  DO NOT INGEST, only use topically.
• Triphala - mixture of 3 fruits, mild laxative effect but does not cause dependency even if taken regularly.
• Turmeric - anti-inflammatory; main ingredient is curcumin (see curcumin above, including safety concern regarding extracts) 
• Dosage is 1.5-3 grams per day in 2 or 3 divided doses. 
• This is an alternative to NSAIDs.
• May interact with coumadin, may increase the risk of calcium oxalate kidney stones (Am J Clin Nutr. 2008. 87. 1262-1267), contraindicated in pregnancy.
• Uva ursi (bearberry) - irritation and inflammation of the urinary tract.  Considered to be bacteriostatic. Dose of tincture (1:5) is 4-6 ml TID, dose of fluid extract (1:1) is 0.5-2 ml TID.
• Valerian     Note excellent review articles in (American Family Physician. 2003. 67. 1755-1758; Alt Med Alert. 2007. 10. 109-113)
• Uses:
• Acute insomnia - The evidence for a single dose effect is contradictory, but predominantly negative.
• Chronic insomnia - Research has focused on subjective evaluations of sleep patterns, and study populations have primarily consisted of self-described poor sleepers. 
• There are numerous clinical trials, at least 62 published as of 2007, and some of these trials are positive (Pharm Biochem Behav. 1989. 32. 1065-1066; Pharmacopsychiatry. 1994. 27. 147-151; Pharmacopsychiatry. 2000. 33. 47-53). The latter study showed no significant effect after a single dose, but a significant effect at the end of 14 days. 
• A systematic review of 9 RCT's concludes that the data is inconclusive, and that more rigorous trials are necessary (Sleep Med. 2000. 1. 91-99). 
• A multicenter 6 week RCT published after the systematic analysis compared 600 mg of valerian extract with 10 mg of oxazepam in 202 patients diagnosed with non-organic insomnia and found that the two agents were equally effective in increasing sleep quality (Eur J Med Res. 2002. 25. 480-486).
• A systematic review of 16 RCTs (n=1093) found that most studies had methodologic problems, and that the valerian doses, preparations, and length of treatment varied completely. In 6 studies in which the outcome was dichotomous (i.e. sleep either improved or not improved), a statistically significant benefit was seen with valerian treatment, but there was evidence of publication bias in this summary measure (Am J Med. 2006. 119. 1005-1012).
• Onset of action is about 1 hour, so it should be taken 30-60 minutes before bedtime.
• Anxiety - Data supporting this indication are limited, with no published positive RCTs as of 2007.
• Dose: 1-3 gm of valerian root decocted to a tea by soaking in one cup of hot water for 10-15 minutes; or 270-450 mg of aqueous extract; or 300-600 mg of a 70% ethanol extract.  The valerian should smell sweet and aromatic and taste spicy.
• Mechanism of action:
• Animal studies suggest that valerian blocks the breakdown of GABA.
• In a small RCT, two 300 mg tablets of a 5:1 extract of valerian root (Sedonium) given 1 hour before bedtime was shown to reduce sleep latency (time taken to fall asleep) AND to increase the amount of slow wave sleep and REM sleep (benzodiazepines do the opposite with regard to slow wave sleep and REM sleep.
• Safety:
• A RCT including 102 volunteers concluded that neither single nor repeated evening administrations of 600 mg valerian root extract had a negative impact on reaction time, alertness, or concentration the morning after intake (Pharmacopsychiatry. 1999. 32. 235). 
• Additional data suggests that long term use is not associated with hangover, tolerance, rebound insomnia, or addiction (Pharmacopsychiatry. 2000. 33. 47-53).
• Valepotriates in valerian may be mutagenic; water-soluble extracts avoid this issue since these chemicals are not extracted when water is used.
• Contraindicated with barbiturates (phenobarbital). 
• Hepatotoxicity has been reported in some individuals taking multi-ingredient herbal medicines including valerian, but it is unclear whether valerian was truly the culprit (BMJ. 1989. 299. 1156-1157)..
• May inhibit cytochrome P450 3A4; clinical significance unclear. 
• Long term studies of safety are lacking.
• Sedonium is the brand name of a 70% ethanol extract used in some clinical trials; Valdispert is the name of an aqueous extract used in some clinical trials.
• Vitex (chaste tree berry) - treatment of PMS, but may require 6 months of use to note a positive effect.
• A  RCT over 3 menstrual cycles in 170 women, using a dose of one 20 mg tablet of dried extract daily (Ze 440, standardized to casticin, 60% ethanol m/m, extract ratio 6-12:1) in the 86 active patients, and placebo in 84 controls, found that 52% of active patients had a 50% reduction in symptoms (including irritability, anger, headache, bloating, and breast fullness) compared to 24% of controls (p<0.001).  Differences in self assessment and clinical global impression were also statistically significantly better in the active treatment group.   (BMJ. 2001. 322. 134-137).
• Another RCT using the same extract in 43 women followed for 8 menstrual cycles (two baseline, three active treatment, and three post-treatment) and assessed with the validated Moos menstrual distress questionnaire found a 43% reduction in mean score by the end of treatment.  Symptoms gradually returned during the post-treatment phase, but a significant 20 % improvement remained (Arch Gynecol Obstet. 2000. 264. 150-153).
• A RCT in 175 women followed over 3 cycles and comparing the commercial preparation Agnolyt to pyridoxine (vitamin B6) found that scores on the Premenstrual Tension Syndrome Scale significantly decreased in both groups.  At the end of the study, 36% of the Vitex group and 21% of the vitamin B6 group were asymptomatic (Phytomedicine. 1997. 4. 183-189).
• May also be effective in treatment of symptoms of menopause, but no controlled trial data.
• Mechanism of action appears to be a progesterone-modulating effect, via increased LH levels, possibly through an inhibitory action on prolactin, through its dopamine agonist activity.
• Side effects - acneiform rash, urticaria (hives).
• The average dose of Agnolyt used in several published drug monitoring studies including several thousand women was 40 and 42 drops per day on an empty stomach (Gynecol. 1990. 12. 422-425; Therapiewoche Gynakologie. 1992. 5. 60-68). According to Alternative Medicine Alert, 1/04, products should be standardized to 0.6% agnuside.  Dosing options include 0.5-1 gram of dried fruit three times a day, 3.5-4.5 mg/day of dried extract, or 1-5 ml of a 1:5 tincture, or 1-4 ml of a 1:2 extract.
• Femaprin and Agnolyt are the best studied brand names - these are tinctures of Vitex that contain 9 grams of a 1:5 tincture for each 100 grams of aqueous-alcoholic solution - the dose is 4 mg daily.
• Willow bark - precursor to aspirin. 
• Uses:
• A Cochrane review identified 2 RCTs in patients with low back pain and concluded there is evidence of efficacy (Cochrane Database Syst Rev. 2006. CD004504).
• Effective in relieving pain in osteoarthritis of the knee and hip in a RCT
• Dosage: - Take one teaspoon (4 droppersfull) of liquid extract or one capsule standardized to 120-240 mg salicin. 
• Safety - Willow bark use is not associated with serious GI side effects (Am J Med. 2000. 109. 9-14). BEWARE of risk of anaphylaxis in ASA allergic patients (Ann Pharmacother. 2003. 37. 832-835).
• Best studied brand name – Asalixx. Other brand names in clinical trials – Rheumalex, Salix, Salgesic.
• Wormwood – bitter herb which is potentially toxic as per Varro Tyler (Herbs of Choice. 1994) because the volatile oil contains a mixture of thujone and isothujone.
• Yohimbe - effective in treatment of impotence.  Dosage is 5.4 mg TID (Yocon is brand name of prescription medicine). Side effects include agitation, tremors, insomnia, tachycardia, and hypertension, so use with caution.

References

• Barnes J et al. Herbal Medicines: A Guide for Health Care Professionals. 2007.
• Blumenthal M (ed). The Complete German Commission E Monographs. 1998.
• Duke, JA. The Green Pharmacy
• Foster S and Varro Tyler. Tyler’s Honest Herbal
• Fragakis AS. The Health Professional’s Guide to Popular Dietary Supplements. American Dietetic Association. 2003.
• Mason, P. Dietary Supplements. 2009. Pocket Companion Series – concise information on 88 supplements.
• Mills S and K Bone. ABC Clinical Guide to Herbs. 2005. Recipient of ABC award based upon “provides a rational and well-referenced approach to determining the relative safety of many botanicals in the market place and how these herbs can be used responsibly by consumers” as per Mark Blumenthal.
• Murray, Michael. The Healing Power of Herbs
• McCaleb RS et al. The Encyclopedia of Popular Herbs
• Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. 1999.
• Stargrove MB et al. Herb, Nutrient, and Drug Interactions. Clinical Implications and Therapeutic Strategies. 2008. Comprehensive compilation with thousands of references.
• Tyler VE. Herbs of Choice. 1994.

• PDR for Herbal Medicines. Medical Economics Company. 1998.
• PDR for Nutritional Supplements. Medical Economics Company. 2001.

• New England Journal of Medicine. 2002. 347. 1997-1998. Perspective: Herbal Medicines - What's in the Bottle? Straus S.
• New England Journal of Medicine. 2002. 347. 2046-2056. Review Article: Herbal Remedies. De Smet P.
• New England Journal of Medicine. 2002. 347. 2073-2076. Sounding Board: Botanical Medicines - The Need for New Regulation. Marcus DM and Grollman AP.
• Annals of Internal Medicine. 2002. 136. 42-53. The Risk-Benefit Profile of Commonly Used Herbal Therapies: Ginkgo, St. John's wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Ernst E.
• JAMA. 2001. 286. 208-216. Herbal Medicines and Perioperative Care. Ang-Lee MK, Moss J, Yuan C.
• Archives of Internal Medicine. 1998. 158. 2192-2199. Herbs as Medicines.  Winslow LC and Kroll DJ.
• Archives of Internal Medicine. 1998. 158. 2200-2211. Herbal Medicinals. Miller LG.
• Archives of Internal Medicine. 1998. 158. 2225-2234. Herbal Medicine for the Treatment of Cardiovascular Disease. Mashour NH, et al.

• American Botanical Council. http://abc.herbalgram.org Box 201160; Austin, TX 78720
• American Herbal Products Association www.ahpa.org/companies/htm links to companies which conform to this trade group's standards for quality
• Consumer Lab www.consumerlab.com independent analysis of content to see whether what is in the bottle is the same as listed on the label, with a listing of brands that pass and fail for common supplements
• HerbMed www.herbmed.org - free information on herbs including clinical trials. Click on the letter of the alphabet, then click on the herb. Site sponsored by the Alternative Medicine Foundation.
• Herb Research Foundation at www.herbs.org/index
• Herbs A-Z at http://www.nlm.nih.gov/medlineplus/druginfo/herb_All.html
• Memorial Sloan-Kettering Cancer Center Integrative Medicine Service. Unbiased monographs that cite scientific literature   www.mskcc.org/aboutherbs or www.mskcc.org/mskcc/html/11571.cfm?herbsaccept=yes
• Natural Medicines Comprehensive Database www.naturaldatabase.com - each herb reviewed is rated as likely safe, possibly safe, possibly unsafe, or likely unsafe based on a thorough review of published data, which is referenced.  Safety of each herb in pregnancy and lactation is also ranked.  For each possible indication, each herb is rated as likely effective, possibly effective, possibly ineffective, likely ineffective, or insufficient reliable evidence to rate.
• Natural Standard Research Collaboration at Massachusetts General Hospital www.naturalstandard.com - grades safety and efficacy of herbs (i.e. A,B,C,D,F) for various conditions based on rigorously researched evidence-based information.
• NIH Office of Dietary Supplements International Bibliographic Information on Dietary Supplements (IBIDS) at http://ods.od.nih.gov/databases/ibids.html (over 730,000 scientific citations and links to more than 1600 journal web sites, as of 2004)

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