You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.
 

 

CME/CE

Top Herbal Products: Efficacy and Safety Concerns

  • Authors: Darrell T. Hulisz, PharmD
  • THIS ACTIVITY HAS EXPIRED
Start Activity


Target Audience and Goal Statement

This activity is intended for pharmacists, primary care physicians, nurse practitioners, physician assistants, nurses, and all clinicians caring for patients who are likely to be using herbal remedies.

The goal of this activity is to review traditional uses, evidence-based data, mechanisms of action, side effects, contraindications and herb-drug interactions of the most popular herbal products on the US market.

Upon completion of this activity, participants will be able to:

  1. Describe traditional and evidence-based uses of the most commonly used herbal products
  2. Explain the probable mechanisms of action of these therapies
  3. Discuss side effects, contraindications, and drug interactions of the most commonly used herbal products


Disclosures

As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


Author(s)

  • Darrell T. Hulisz, PharmD

    Associate Professor, Department of Family Medicine, Case Western Reserve University School of Medicine, University Hospitals, Case Medical Center, Cleveland, Ohio

    Disclosures

    Disclosure: Darrell T. Hulisz, PharmD, has disclosed that he has received grants for educational activities from Pfizer, Takeda, and Novartis. Dr. Hulisz has also disclosed that he has served as an advisor or consultant for Pfizer, Takeda, and Novartis.

Editor(s)

  • Christine Wiebe, MA

    Editorial Director, Medscape Medical Students and Pharmacists

    Disclosures

    Disclosure: Christine Wiebe has disclosed no relevant financial relationships.

  • Jacqueline A. Hart, MD

    Freelance Clinical Editor, Medscape, LLC, Boston, Massachusetts

    Disclosures

    Disclosure: Jacqueline A. Hart, MD, has disclosed no relevant financial relationships.


Accreditation Statements

    For Physicians

  • Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    Medscape, LLC designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.

    Contact This Provider

    For Nurses

  • This Activity is sponsored by Medscape Continuing Education Provider Unit.

    Medscape is an approved provider of continuing nursing education by the New York State Nurses Association, an accredited approver by the American Nurses Credentialing Center's Commission on Accreditation.

    Awarded 1.0 contact hour(s) of continuing nursing education for RNs and APNs; 1.0 contact hours are in the area of pharmacology.

    Provider Number: 6FDKKC-PRV-05

    Contact This Provider

    For Pharmacists

  • Medscape is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

    Medscape designates this continuing education activity for 1.0 contact hour(s) (0.10 CEUs) (Universal Program Number 461-000-07-082-H01-P).

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit*:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

CME/CE

Top Herbal Products: Efficacy and Safety Concerns

processing....

Valerian, Chamomile, Ginger: Calming Agents

Valerian

Valerian root (Valeriana officinalis) has been used for centuries for its calming effects. Medics gave it to soldiers during World War I for the treatment of shell shock.[87,88] The active ingredients appear to be valepotriates (thought to be responsible for the sedative effects) and valeric acid, both of which mediate the release of gamma-aminobutyric acid. Randomized clinical trials have demonstrated efficacy of valerian root extract for treating insomnia.[89,90]

Mild side effects have included paradoxical stimulation (restlessness and palpitations), especially with long-term use. Valerian should not be used in pregnancy. This herb may have an additive effect with other central nervous system depressants. Patients should be cautioned regarding the operation of machinery when initiating therapy until they are accustomed to the effects. Other potential side effects include headaches, excitability, and uneasiness. Typical dosages for insomnia are 200-400 mg (standardized to 0.8%-1% valeric acids per dose) at bedtime.

Chamomile

Few human studies have been published on the use of chamomile (Matricaria recutita), yet it is cultivated worldwide for its sedating and calming properties. The active component apigenin has been shown to bind the same receptors as benzodiazepines, to exert an anxiolytic and mild sedative effect in mice.[91] Chamomile also has moderate antioxidant, antimicrobial, and antiplatelet activity in vitro.[92]

Chamomile is considered safe by the FDA, but it should be used with caution in individuals who are allergic to ragweed, as cross-allergenicity may occur. Allergic symptoms include tongue thickness, tight sensation in throat, angioedema of lips and eyes, diffuse pruritis, urticaria, and pharyngeal edema.[93,94] Because of its sedative effects, chamomile should be used with caution when taken in conjunction with medications that have also sedative side effects, or with alcohol. Oral doses vary from 400 to 1600 mg per day (standardized to 1.2% apigenin per dose). Chamomile is often brewed as a tea; 1 heaping teaspoon of dried flowers steeped in hot water for 10 minutes may be drunk up to 3 times a day.

Ginger

Ginger (Zingiber officinale) is cultivated in Asia, Africa, and the Caribbean. It has been used for centuries as a flavoring agent and for its antiemetic properties. The root produces a volatile oil containing shogaol and gingerol.[95] Gingerol and shogaol have demonstrated analgesic, anti-inflammatory, sedative, antipyretic, and antitussive properties in vitro and in animals, as well as antioxidant antimicrobial, antifungal, antineoplastic, and antihypertensive benefits; many of these effects have yet to be tested in people, however.[96] Human studies have shown a significant reduction in nausea in patients with hyperemesis gravidarum taking doses of 250 mg 4 times a day,[96-98] and in patients with perioperative nausea and vomiting taking doses of 1 g prior to surgery.[99,100] A study comparing ginger with 100 mg dimenhydrinate and with placebo found that ginger was superior to both when patients were subjected to a revolving chair designed to produce motion sickness.[101]

Ginger has exhibited inhibition of thromboxane synthetase that resulted in prolonged bleeding.[102] Therefore, it is prudent for those taking anticoagulants to have their International Normalized Ratio (INR) monitored closely. Ginger can also cause mild gastrointestinal (GI) upset including heartburn, diarrhea, and mouth irritation.[96]

Take-home message: Valerian, chamomile, and ginger can be safely recommended in the majority of patients. These agents have shown modest efficacy for their primary uses. However, patients with chronic anxiety and insomnia should be under the care of a healthcare professional and thus should not attempt self-medication with botanicals.

Ginseng: A Natural Energy Booster

The term ginseng (Panax ginseng, Panax quinquefolius) means "man-root," and the ancient Chinese believed it could benefit all aspects of the human body; today, it is mostly used as an energy booster.[103] "Siberian ginseng" is derived from the Eleutherococcus senticosos shrub and has different properties than ginseng from the Panax family[104]; in fact, federal regulation now requires that this product be referred to as eleuthero to distinguish the 2 herbs.[105]

Derived from the root of the plant, the ginsenosides found in ginseng are a compilation of more than 20 saponin triterpenes and are thought to be the active ingredients.[106] Animal studies suggest that these steroid-like compounds work by stimulating the secretion of adrenocorticotropic hormone, resulting in increased production of cortisol.[107] The herb may also play a role in stimulating the production of adrenal hormone precursors.

Ginseng is considered by many to enhance physical, sexual, and mental performance, as well as increase resistance to stress. Because these potential benefits are somewhat subjective, however, controlled clinical trials are difficult to interpret. Generally speaking, results from clinical trials have been equivocal.[103]

Although it is much too early to tell how this may affect people with diabetes, animal studies suggest that ginseng may reduce glucose levels in obese, diabetic mice.[108,109]

Because it can have a mild stimulant effect, it should be avoided by patients with cardiovascular disease who are taking other stimulants. Ginseng has also been associated with reversible mastalgia and postmenopausal bleeding, although this appears to be a rare side effect.[110] Overuse of ginseng may be associated with diarrhea, hypertension, nervousness, dermatologic eruptions, and insomnia. This herb has also been associated with a reduction in the INR of warfarin-treated patients.[111] In addition, ginseng has been associated with altered hemostasis and is therefore contraindicated in patients with active bleeding; patients receiving anticoagulant and/or antiplatelet medications should be cautioned against using ginseng.[112]

As with many other herbs, ginseng formulations have not been standardized, nor have optimal doses been determined, but common regimens involve 100-600 mg per day in divided doses.

Take-home message: Historically, many claims have been made by supporters of Panax ginseng formulations; however, robust clinical trials are lacking. Patients who use ginseng should be cautioned not to exceed the labeled dosage since adverse effects may occur. Clinicians should discourage use in patients who are anticoagulated, and those with cardiovascular or metabolic disease, such as hypertension and diabetes.

Saw Palmetto: Effective for Benign Prostatic Hyperplasia?

The extract for saw palmetto (Serenoa repens) comes from the fruit of the palm tree and is often used to treat benign prostatic hyperplasia (BPH). Saw Palmetto extract is thought to inhibit 5-alpha reductase and thus block the conversion of testosterone to dihydrotestosterone, which is responsible for stimulating growth of the prostate gland.[113] It also blocks the uptake of both hormones by the prostate. Saw palmetto may exhibit some anti-inflammatory effects, presumably by inhibiting cyclooxygenase pathways.[114]

While early clinical studies suggested a modest benefit of saw palmetto in BPH, more recent studies are less consistent, and the precise clinical value of saw palmetto for treating urinary symptoms remains undefined.[115,116] In a recent randomized, double-blind, placebo-controlled trial, 225 men were given either standardized saw palmetto 160 mg twice daily or placebo for 1 year.[116] There was no significant difference between the 2 groups in the change in objective urologic symptom scores, maximal urinary flow rate, prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels. The incidence of side effects was similar in the 2 groups.

Side effects are uncommon with saw palmetto, but they may include headache and GI upset. There are no known important drug interactions with this herb.[113] The most commonly used dose for treating BPH is 160 mg twice daily.

Take-home message: Men with obstructive urinary symptoms should not self-medicate with saw palmetto. Such patients should be under medical supervision, because the symptoms of BPH can mimic other, more serious disorders, such as prostate cancer and prostatitis. This herb should be reserved for men with mild BPH symptoms who have an aversion to prescription drugs and are also under medical care.

Black Cohosh Used to Ease Hot Flashes

Black cohosh (Cimicifuga racemosa) is a plant native to Eastern North America. It contains a group of chemicals referred to as phytoestrogens because they mimic the effects of estrogens. For this reason it was a common remedy used by Native Americans for the treatment of painful menses (known as squawroot).

Recent clinical trials indicate that black cohosh is somewhat efficacious in relieving menopause symptoms.[117-121] The majority of the trials used the isopropranolic extract of black cohosh at a total dose of 40-80 mg daily. Most studies were only conducted for a short duration of either 3 or 6 months. Thus, further clinical trials are needed to assess efficacy of black cohosh beyond 6 months. Recent investigations do not support the earlier estrogen-receptor mediated theory as a plausible mechanism of action of black cohosh including a randomized, placebo-controlled, 1-year study of 351 women with menopausal symptoms failed to confirm efficacy of black cohosh.[122]

Black cohosh is generally considered safe without any major life-threatening adverse events.[121] Some patients may experience mild side effects including rash or GI upset. It should not be used in lactating or pregnant women. Since there is still speculation of an estrogen-like effect, black cohosh use should be avoided in women with a history of estrogen-dependent tumors or endometrial cancer. Most authorities suggest limiting its use to 6 months because no long-term trials have been conducted. Black cohosh offers an alternative to estrogen for symptoms of menopause, the most widely studied dose is 20-40 mg twice daily standardized to 1 mg triterpene glycosides.

Take-home message: Clinical trials using black cohosh to relieve menopausal symptoms have yielded conflicting results. However, some women experience benefits with the herb without apparent side effects. It appears to be safe, but use should be limited to no more than 6 months and should not be used in those with a history of estrogen-dependent tumors.

Conclusion

Consumers with serious or chronic health complaints will often self-diagnose and self-treat with herbs and supplements. This is not ideal, because many of these patients need supervised medical care, especially those with depression, prostate disease, dementia, or chronic insomnia.

Health professionals generally should advise against the use of herbs or supplements during pregnancy or lactation, because the effects on fetal development and breast milk excretion are unknown. Similarly, use in infants and younger children should be discouraged.

Patients should be advised to take the same dosages that have been studied in clinical trials, and not to exceed labeled amounts. Generally, herbs should be consumed only for a limited time. Patients should avoid products with labels that fail to specify the exact amount of the herb contained per dosage unit.

Health professionals should elicit a careful history from patients regarding any plant allergies, especially to ragweed and daisies, recalling that many patients with allergic rhinitis may not know what allergens trigger their attacks. Patients who are allergic to ragweed and flowers in the daisy family (asters, chrysanthemums) may have allergic reactions to products containing echinacea and chamomile. Some herbs are photosensitizing (eg, St. John's wort), and patients should be cautioned appropriately (especially fair-skinned individuals).

Patients anticipating surgical procedures should discontinue use of herbs at least 2 weeks prior to surgery, and should notify the anesthesiologist of any routine herb usage.[54] As discussed, some herbals may interfere with normal blood coagulation, predisposing patients to prolonged bleeding and interactions with warfarin (eg, garlic, ginkgo, ginseng, and ginger).


References

References

  1. Kennedy J. Herb and supplement use in the US adult population. Clin Ther. 2005;27:1847-1858. Abstract
  2. Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. N Engl J Med. 1993;328:246-252. Abstract
  3. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997. JAMA. 1998;280:1569-1575. Abstract
  4. Tindle HA, Davis RB, Phillips RS, Eisenberg DM. Trends in use of complementary and alternative medicine by US adults: 1997-2002. Altern Ther Health Med. 2005;11:42-49.
  5. Tyler VE. What pharmacists should know about herbal remedies. J Am Pharm Assoc. 1996;NS36:29-37.
  6. Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician. 1999;59:1239-1244. Abstract
  7. Borins M. The dangers of using herbs: what your patients need to know. Postgrad Med. 1998;104:91-100.
  8. DeSmet PAGM. Herbal remedies. Review. N Engl J Med. 2002;347:2046-2056. Abstract
  9. Dunbabin DW, Tallis GA, Popplewell PY, et al. Lead poisoning from Indian herbal medicine (Ayurveda). Med J Aust. 1992;157:835-836. Abstract
  10. Markowitz SB, Nunez CM, Klitzman S, et al. Lead poisoning due to hai ge fen: the porphyrin content of individual erythrocytes. JAMA. 1994;271:932-934. Abstract
  11. Zayas LH, Ozuah PO. Mercury use in espiritismo: a survey of botanicas (letter). Am J Public Health. 1996;86:111-112. Abstract
  12. Gertner E, Marshall PS, Filandrinos D, et al. Complications resulting from the use of Chinese herbal medications containing undeclared prescription drugs. Arthritis Rheum. 1995;38:614-616. Abstract
  13. Hughes JR, Higgens EM, Pembrooke AC. Oral dexamethasone masquerading as a Chinese herbal remedy. Br J Dermatol. 1994;130:261.
  14. Graham-Brown RA, Bourke JF, Bumphrey G. Chinese herbal remedies may contain steroids. BMJ. 1994;308:473.
  15. Stricht BV, Pavais OE, Vanhaelen-Fastre RJ, et al. Remedies may contain cocktail of active drugs. BMJ. 1994;308:1162.
  16. Schaumburg HH, Berger A. Alopecia and sensory polyneuropathy from thallium in a Chinese herbal medication. JAMA. 1992;268:3430-3431. Abstract
  17. Bogusz MJ, al Tufail M, Hassan H. How natural are 'natural herbal remedies'? A Saudi perspective. Adverse Drug React Toxicol Rev. 2002;21:219-229. Abstract
  18. 103d Congress, 2nd Session, Senate. The Dietary Supplement Health and Education Act of 1994. Washington, Report 103-410;1994:1-49.
  19. Rados C. Ephedra ban: no shortage of reasons. FDA Consumer Magazine. March-April 2004. Available at: http://www.fda.gov/FDAC/features/2004/204_ephedra.html Accessed November 19, 2007.
  20. CDC. Hepatic toxicity possibly associated with Kava-containing products - United States, Germany, and Switzerland, 1999-2002. MMWR Weekly. November 29, 2002;51:1065-1067. Available at: http://www.cdc.gov/MMWR/preview/mmwrhtml/mm5147a1.htm Accessed November 19, 2007.
  21. American Cancer Society. Saw Palmetto. Available at: http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Saw_Palmetto.asp?sitearea=ETO Accessed December 1, 2007.
  22. Turner RB. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med. 2005;353:341-348. Abstract
  23. Schoop R, Klein P, Suter A, Johnston SL. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis. Clin Ther. 2006;28:174-183. Abstract
  24. Braunig B, Dorn M, Linburg E, Knick E. Enhancement of resistance in common colds by Echinacea purpurea. Z Phytother.1992;13:7-13.
  25. Schoneberger D. Influence of the immunostimulating effects of the pressed juice of Echinacea purpureae on the duration and intensity of the common cold: results of a double-blind clinical trial. Forum Immunol. 1992;2:18-22.
  26. Bielory L. Adverse reactions to complementary and alternative medicine: ragweed's cousin, the coneflower (echinacea) is "a problem more than a sneeze." Ann Allergy Asthma Immunol. 2002;88:7-9.
  27. Mullins RJ, Heddle R. Adverse reactions associated with Echinacea: the Australian experience. Ann Allergy Asthma Immunol. 2002;88:42-51. Abstract
  28. Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol. 2004;140:723-727. Abstract
  29. Alternative remedies may activate autoimmune disorders. Health News. 2004;10:15.
  30. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-2211. Abstract
  31. Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D'Alessio D. Treatment of the common cold with unrefined Echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002;137:939-946. Abstract
  32. Linde K, Barrett B, Wolkart K, Bauer R, Melchart D. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2006;CD000530.
  33. Lawson D. Human medicinal agents from plants. Springville, Utah: American Chemical Society; 1993.
  34. Jain A, Vargas R, Gotzkowsky S, McMahon F. Can garlic reduce the levels of serum lipids? A controlled clinical study. Am J Med. 1993;94:632-635. Abstract
  35. Adler AJ, Holub BJ. Effect of garlic and fish oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men. Am J Clin Nutr.1997;65:445-450. Abstract
  36. Steiner M, Khan AH, Holbert D. Lin R. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr. 1996;64:866-870. Abstract
  37. Byrne Dj, Neil HA, Vallance DT, et al. A pilot study of garlic consumption shows no significant effect on markers of oxidation or sub-fraction composition of low-density lipoprotein including lipoprotein(a) after allowance for non-compliance and the placebo effect. Clin Chim Acta. 1999;285:21-33. Abstract
  38. Berthold HK, Sudhop T, von Bergmann K. Effect of garlic oil preparation on serum lipoproteins and cholesterol metabolism: a randomized controlled trial. JAMA. 1998;279:1900-1902. Abstract
  39. Isaacsohn JL, Moser M, Stein EA, et al. Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial. Arch Intern Med. 1998;158:1189-1194. Abstract
  40. Aue W, Eiber W, Hhertkorn E, et al. Hypertension and hyperlipidemia: garlic helps in mild cases. Br J Clin Pract. 1990;69:3-6.
  41. Silagy C, Neil A. A meta analysis of the effect of garlic on blood pressure. J Hypertens. 1994;12:463-468. Abstract
  42. Silagy CA, Neil AW. A meta-analysis of the effect of garlic on blood pressure. J Hypertens.1994;12:463-468. Abstract
  43. Scharbert G, Kalb l, Duris M, Marschalek C, Kozek-Langenecker SA. Garlic at dietary doses does not impair platelet function. Anesth Analg. 2007;105:1214-1218. Abstract
  44. Allison GL, Lowe GM, Rahman K. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr. 2006;136:782S-788S. Abstract
  45. Rahman K. Effects of garlic on platelet biochemistry and physiology. Mol Nutr Food Res. 2007;51:1335-1344. Abstract
  46. Steiner M, Li W. Aged garlic extract, a modulator of cardiovascular risk factors : a dose-finding study on the effects of AGE on platelet functions. J Nutr. 2001;131:980S-984S. Abstract
  47. Elmer GW, Lafferty WE, Tyree PT, Lind BK. Potential interactios between complementary/alternative products and conventional medicines in Medicare population. Ann Pharmacother. 2007;41:1617-1624. Epub 2007 September 4.
  48. Rose KD, Croissant PD, Parliament CF, Levin MP. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery 1990;26:880-882.
  49. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61:2163-2175. Abstract
  50. Evans V. Herbs and the brain: friend or foe? The effects of ginkgo and garlic on warfarin use. J Neurosci Nurs. 2000;32:229-232. Abstract
  51. Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355:134-138. Abstract
  52. Vaes LP, Chyka PA. Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Ann Pharmacother. 2000;34:1478-1482. Abstract
  53. Macan H, Uykimpang R, Alconcel M, et al. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr. 2006;136:793S-795S. Abstract
  54. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA. 2001;286:208-216. Abstract
  55. Staba EJ, Lash L, Staba JE. A commentary on the effects of garlic extraction and formulation on product composition. J Nutr. 2001;131:1118S-1119S. Abstract
  56. Le Bars P, Katz M, Berman N, Turan M, Freedman A, Schatzberg A. A placebo-controlled , double-blind, randomized trial of an extract of ginkgo biloba for dementia. JAMA. 1997;278:1327-1332. Abstract
  57. Hindemarch I, Subhan Z. The pharmacological effects of ginkgo biloba extract in normal healthy volunteers. Int J Clin Pharmacol Res. 1984;4:89-93. Abstract
  58. Ernest E. Ginkgo biloba extract in peripheral artery diseases: a systemic research based on controlled studies in the literature. Fortsch Med. 1996;114:85-87.
  59. Carlson JJ, Farquhar JW, DiNucci E, et al. Safety and efficacy of a ginkgo biloba-containing dietary supplement on cognitive function, quality of life, and platelet function in healthy, cognitively intact older adults. J Am Diet Assoc. 2007;107:422-432. Abstract
  60. Rowim J, Lewis SL. Spontaneous bilateral hematomas associated with chronic ginkgo biloba ingestion have also occurred. Neurology. 1996;46:1775-1776. Abstract
  61. Woerdengag HJ, Van Beck TA. Ginkgo biloba. Adverse Effects of Herbal Drugs. Vol 3. Berlin, Germany: Springer-Verlag; 1997.
  62. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of ginkgo biloba extract (letter). N Engl J Med. 1997;336:1108.
  63. Chung KF, McCusker M, Page CP, Dent G, Guinoit P, Barnes PJ. Effect of ginkolide mixture in antagonizing skin and platelet responses to platelet activating factor in man. Lancet. 1987;1:248-251. Abstract
  64. Granger AS. Ginkgo biloba precipitating epileptic seizures. Age Ageing. 2001;30:523-525. Abstract
  65. Spinella M. Herbal medicines and epilepsy: the potential for benefit and adverse effects Epilepsy Behav. 2001;2:524-532.
  66. Harms SL, Garrard J, Schwinghammer P, Eberly LE, Chang Y, Leppik IE. Ginkgo biloba use in nursing home elderly with epilepsy or seizure disorder. Epilepsia. 2006;47:323-329. Abstract
  67. Kupiec T, Raj V. Fatal seizures due to potential herb-drug interactions with Ginkgo biloba. J Anal Toxicol. 2005;29:755-758. Abstract
  68. Mazza M, Capuano A, Bria P, Mazza S. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. Eur J Neurol. 2006;13:981-985. Abstract
  69. Muller W. Effects of Hypericum extract on the suppression of serotonin receptors. J Geriat Psychiatry Neurol. 1994;7:s63-64.
  70. Muller WE, Rolli M, Schafer C, Hafner U. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry. 1997;30:102-107. Abstract
  71. Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. 2006;39:66-75. Abstract
  72. Linda K, Gilber R, Murlow C, Paulis A, Weidenhammer W, Meichart D. St. John's wort for depression: an overview and meta-analysis of randomized trials. BMJ. 1996;313:253-257. Abstract
  73. Fava M, Alpert J, Nierenberg AA, et al. A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005;25:441-447. Abstract
  74. Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002;159:1361-1366. Abstract
  75. Barnes J, Anderson LA, Phillipson JD. St John's wort (Hypercum perforatum L.): a review of its chemistry pharmacology and clinical properties. J Pharm Pharmacol. 2001;53:583-600. Abstract
  76. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol. 2004;18:262-276. Abstract
  77. Izzo AA. Drug interactions with St. John's wort (Hypericum perforatum): a review of the clinical evidence. Int J Clin Pharmacol Ther. 2004;42:139-148. Abstract
  78. Grush LR, Nierenberg A, Keefe B, et al. St. John's wort during pregnancy. JAMA. 1998;280:1566.
  79. Duqoua JJ, Mills E, Perri D, Korean G. Safety and efficacy of St. John's wort (hypericum) during pregnancy and lactation. Can J Clin Pharmacol. 2006;13:e268-e276. Abstract
  80. Lane-Brown MM. Photosensitivity associated with herbal preparations of St John's wort (Hypericum perforatum). Med J Aust. 2000;172:302.
  81. Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin Pharmacol Ther. 1999;66:338-345. Abstract
  82. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St. John's wort. Lancet. 2000;355:547-548. Abstract
  83. Piscetelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John's wort. Lancet. 2000;355:547-548. Abstract
  84. Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noil G. Acute heart transplant rejection due to St. John's wort. Lancet. 2000;355:548-549. Abstract
  85. Mannel M. Drug interactions with St John's wort: mechanisms and clinical implications. Drug Saf. 2004;27:773-797. Abstract
  86. Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J. Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol. 2003;56:683-90. Abstract
  87. Hardy ML. Valerian root for insomnia. Alternative Medicine Alert. 1999;2:85.
  88. Brevcort P. The booming US botanical market: a new overview. HerbalGram. 1998;44:33-48.
  89. Ziegler G, Ploch M, Miettinen-Baumann A, Collet W. Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia -- a randomized, double-blind, comparative clinical study. Eur J Med Res. 2002;7:480-486. Abstract
  90. Donath F, Quispe S, Diefenbach K, Maurer A, Fietze I, Roots I. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry 2000;33:47-53.
  91. Viola H, Wasowski C, Levi de Stein M, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazopine receptor-ligand with anxiolytic effects. Planta Med. 1995;61:213-216. Abstract
  92. McKay DL, Blumberg JB. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res. 2006;20:519-530. Abstract
  93. Casterline CL. Allergy to chamomile tea. JAMA. 1980;4:330-331.
  94. Benner MH, Lee HJ,. Anaphylactic reaction to chamomile tea. J Allergy Clin Immunol. 1973;52:307-308. Abstract
  95. Monograph: Zingiber officinale (Ginger). Altern Med Review. 2003;8:331-335.
  96. White B. Ginger: an overview. Am Fam Physician. 2007;75:1689-1691. Abstract
  97. Boone SA, Shields KM. Treating pregnancy-related nausea and vomiting with ginger. Ann Pharmacother. 2005;39:1710-1713. Epub 2005 August 30.
  98. Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005;105:849-856. Abstract
  99. Phillips S, Ruggier R, Hutchinson S. Zingiber oficinale (ginger): an antiemetic for day of surgery. Anaesthesia. 1993;48:715-717. Abstract
  100. Bone M, Wilkinson D, Young J, Charlton S. The effect of ginger root on postoperative nausea and vomiting after major gynecologic surgery. Aneaesthesia. 1990;45:669-671.
  101. Mowrey DB, Clayson DE. Motion sickness, ginger and psychophysics. Lancet. 1982;1:655-657. Abstract
  102. Backon J. Ginger: inhibition of thromboxane synthetase and stimulation of prostacycline: relevance for medicine and psychiatry. Med Hypothesis. 1986;20:271-278.
  103. Coleman CI, Hebert JH, Reddy P. The effects of Panax ginseng on quality of life. J Clin Pharm Ther. 2003;28:5-15. Abstract
  104. Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman RM. Variability in commercial ginseng products: an analysis of 25 preparations. Am J Clin Nutr. 2001;73:1101-1106. Abstract
  105. New Law Limits Use of Term "Ginseng." 13 August 2002. Available at: http://www.supplementquality.com/news/ginseng_law.html Accessed November 29, 2007.
  106. Radad K, Gille G, Liu L, Rausch WD. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci. 2006;100:175-186. Epub 2006 March 4.
  107. Kim DH, Moon YS, Jung JS, Min S. Effects of ginseng saponin administered intraperitoneally on the hypothalamo-pituitary-adrenal axis in mice. Neurosci Lett. 2003;343:62-66. Abstract
  108. Xie JT, Wang CZ, Ni M, et al. American ginseng berry juice intake reduces blood glucose and body weight in ob/ob mice. J Food Sci. 2007;72:S590-S594. Abstract
  109. Yoon SH, Han EJ, Sung JH, Chung SH. Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice. Biol Pharm Bull. 2007;30:2196-2200. Abstract
  110. Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician. 2003;68:1539-1542 Abstract
  111. Yuan CS, Wei G, Dey L, et al. Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled Trial. Ann Intern Med. 2004;141:23-27. Abstract
  112. Kuo SC, Teng CM, Lee JC, Ko FN, Chen SC, Wu TS. Antiplatelet components in Panax ginseng. Planta Med. 1990;56:164-167. Abstract
  113. Gordon AE, Shaughnessy AF. Saw palmetto for prostate disorders. Am Fam Physician. 2003;67:1281-1283. Abstract
  114. Buck AC. Is there a scientific basis for the therapeutic effects of serenoa repens in benign prostatic hyperplasia? Mechanisms of action. J Urol. 2004;172:1792-1799. Abstract
  115. Avins AL, Bent S. Saw palmetto and lower urinary tract symptoms: what is the latest evidence? Curr Urol Rep. 2006;7:260-226.
  116. Bent S, Kane C, Shinohara K, et al. Saw palmetto for benign prostatic hyperplasia. N Engl J Med. 2006;354:557-566. Abstract
  117. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol. 2001;19:2739-2745. Abstract
  118. Wuttke W, Seidlova-wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas. 2003;44:S67-S77. Abstract
  119. Frei-Kleiner S, Schaffner W, Rahlfs VW, Bodmer CH, Birkhauser M. Cimicifuga racemosa dried ethanolic extract in menopausal disorder: a double-blind placebo-controlled clinical trial. Maturitas. 2005;51:397-404. Abstract
  120. Nappi RE, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol. 2005;20:30-35. Abstract
  121. Osmers R, Friede M, Liske E, Schnitker J, Freudenstein J,Henneicke-von Zepelin HH. Efficacy and safety of ispropranolic black cohosh extract for climacteric symptoms. Obstet Gynecol. 2005;105:1074-1083. Abstract
  122. Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145:869-879. Abstract