Research Database –
International Updates

Herbal Medicine

Issue 57

BERMAN, SWYERS and KACZMARCZYK, Department of Family Medicine, University of Maryland School of Medicine, Baltimore, James L. Kerman Hospital 21207-6697, USA discussed herbal therapies for diabetes.
Discussion: Interest in and use of complementary and alternative medicine (CAM) have increased in recent years, with as much as 40% of the general population having used some form of CAM in the past year. Although recent national surveys have not adequately assessed the use of CAM in minority populations, its use in these populations is at least equal to and possibly greater than that in the general population. One condition for which minority populations are likely to use CAM therapies is diabetes, which is particularly prevalent in Mexican-American and Native-American communities. Many minority cultures have a long history of using herbal preparations to treat diabetes, and recent research suggests that some of these are efficacious. However, many questions remain regarding the proper use of herbal therapies for diabetes, particularly in regard to dosage and contaminants. Therefore, physicians who work with minority populations should ask patients about their use of these therapies and must become knowledgeable about their safety and efficacy.
Berman BM et al. Complementary and alternative medicine: herbal therapies for diabetes. Journal of the Association of Academic Minority Physicians 10(1): 10-14. 1999.

ERNST and HUNTLEY, Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK. E.Ernst@ex.ac.uk conducted a systematic review (23 references) on tea-tree oil.
Background: Tea tree oil (TTO) is immensely popular for various topical applications. In vitro studies have repeatedly demonstrated that it has antibiotic activity. This article was an attempt to systematically review the evidence from randomized clinical trials for or against effectiveness of external TTO in dermatological conditions.
Methods: Six electronic databases were searched. Methodological quality was assessed by Jadad score. Data were extracted and validated in a standardized fashion by two independent reviewers.
Results: Four trials were located. They suggest that TTO may be effective as a treatment of acne and fungal infections. The adverse effects of TTO are usually mild and transient. They mainly consist of allergic reactions.
Conclusions: The authors concluded that, so far, there is no compelling evidence to show that TTO is efficacious in any dermatological condition. However, in view of promising findings, TTO deserves to be investigated more closely.
Ernst E and Huntley A. Tea tree oil: a systematic review of randomized clinical trials. Forschende Komplementarmedizin 7(1): 17-20. Feb 2000.

PATZELT-WENCZLER and PONCE-POSCHL, ASTA Medica AG, Weismullerstr. 45, D-60314 Frankfurt am Main, Germany. Dr_Jeannette.Simon@astamedica.de conducted a trial into the efficacy of Kamillosan® cream in atopic eczema.
Background: Kamillosan® cream contains chamomile extract as an active principle manufactured from the chamomile sort Manzana and has been proved not to exhibit a chamomile-related allergen potential. For this reason Kamillosan® cream is suited for local therapy of atopic eczema.
Methods: In a partially double-blind, randomized study carried out as a half-side comparison, Kamillosan® cream was tested vs. 0.5% hydrocortisone cream and the vehicle cream as placebo in patients suffering from medium-degree atopic eczema.
Results: After a two-week treatment Kamillosan® cream showed a mild superiority towards 0.5% hydrocortisone and a marginal difference as compared to placebo.
Patzelt-Wenczler R and Ponce-Poschl E. Proof of efficacy of Kamillosan® cream in atopic eczema. European Journal of Medical Research 5(4): 171-5. Apr 2000.

Comment: There is a large amount of anecdotal writings on the use of chamomile for skin conditions such as eczema so it is good news to see a clinical trial showing that it may be comparable to a hydrocortisone cream.

LAKE, InnoVision Communications, Aliso Viejo, CA 92656, USA reviewed (112 references) the research and recommendations for psychotropic medications from natural products.
Background: Most psychotropic agents employed in allopathic medicine have limited efficacy and significant side effects. Although usually beneficial, synthetic psychotropics are unavailable to approximately 80% of the world's population. Improved understanding of appropriate and safe uses of naturally occurring psychotropic agents will greatly contribute to global mental healthcare. Empirical validation of non-allopathic treatments to ensure safety and efficacy is important because increasing numbers of patients in economically developed countries are using natural substances as medicinal agents. Patients and clinicians often lack accurate information, resulting in poor treatment outcomes or the possibility of drug-drug interactions of herbal and synthetic psychotropic medications. The authors aimed to distinguish compelling scientific evidence supporting the use of natural products in psychiatry from political or institutional biases that have been misrepresented as scientific arguments.
Methods: A systematic literature review on natural products used to treat neuropsychiatric disorders. Significant recent research is reviewed, including emerging treatments of seizure disorders, schizophrenia, dementia and age-related cognitive decline, depression, anxiety states, and substance abuse. Substantial evidence is advanced for safety and efficacy of many natural products used to treat neuropsychiatric symptoms or disorders.
Results: Preliminary findings suggest that several treatments based on natural substances are as effective and safe as synthetic pharmaceuticals in current use. Additional studies are indicated to confirm these findings, to elucidate mechanisms of action, and to elaborate standards for safe and appropriate treatment indications.
Conclusions: Strategic approaches aimed at facilitating improved networking, accelerating promising research directions, and enhancing quality standards of ongoing investigations into putative psychotropic agents from natural sources are recommended.
Lake J. Psychotropic medications from natural products: a review of promising research and recommendations. Alternative Therapies in Health and Medicine 6(3):36, 39-45, 47-52 passim. May 2000.

Issue 56

EINARSON and colleagues, The Motherisk Program, The Hospital for Sick Children, Toronto, Canada. einarson@sickkids.on.ca described and compared attitudes and practices of physicians and naturopaths toward herbal medicine.
Background: As the popularity of complementary therapies continues to grow, physicians are asked increasingly by their patients for information regarding these treatments. The aim of this study was to compare the impact of these trends on the attitudes and practices of physicians and naturopaths, and their students, with a particular interest in the use of herbal products during pregnancy and breastfeeding.
Methods: A detailed questionnaire was distributed by a medical student and a naturopathic student to a randomly selected group of physicians, medical students, naturopaths and naturopathic students. They were asked a variety of questions about their background, attitudes and practices concerning herbal products.
Results: Thirty-eight per cent of the questionnaires were returned, with a total of 242 respondents. Fifty-four per cent of physicians discussed complementary therapies with their patients, whereas 100% of naturopaths discussed conventional medicines with their patients. The most popular product recommended by both medical doctors and naturopaths was echinacea, followed by St John's Wort. Eighty-six per cent of physicians, 74% of medical students, 66% of naturopaths and 50% of naturopathic students think that complementary medical education should be incorporated into the standard medical curriculum. One physician recommended a herbal product to a pregnant patient compared with 49% of the naturopaths.
Conclusions: Complementary medicine has become a reality, and physicians are recommending herbal products to their patients, although on a smaller scale than are naturopaths. Physicians are less likely to recommend herbal products to pregnant and breastfeeding women than are naturopaths.
Einarson A et al. Attitudes and practices of physicians and naturopaths toward herbal products, including use during pregnancy and lactation. The Canadian Journal of Clinical Pharmacology 7(1): 45-9. Spring 2000.

GRAF, Department of Dermatology, New York University Medical Center, New York, New York, USA set out to describe the use of anti-inflammatory effects of some herbal medicine for skin disease.
Discussion: The authors discuss how although herbs have been used in clinical medicine for thousands of years, it is only in recent times that we have been able to employ scientific methods to prove the efficacy of many of these herbs and to give us a better understanding of their mechanisms of action. The article focuses on the use of herbs in various dermatological conditions, characterized by inflammation and pruritus. Topical preparations of many of these herbs are more commonplace in Europe; however, their availability is increasing in the US. The author concludes that these discoveries are bringing alternative and traditional medicines closer together.
Graf J. Herbal anti-inflammatory agents for skin disease. Skin Therapy Letters 5(4): 3-5. 2000.

MANN, COX and MARKHAM, Centre for Biostructural and Biomolecular Research, University of Western Sydney, Sydney, NSW, Australia. c.mann@uws.edu.au described how the outer membrane of Pseudomonas aeruginosa protects it against the action of tea tree oil (Melaleuca alternifolia).
Background: Tea tree oil is well known and widely used for its antiseptic properties.
Discussion: Pseudomonas aeruginosa is less susceptible to the antimicrobial properties of tea tree oil than many bacteria and its tolerance is considered to be due to its outer membrane. Polymyxin B nonapeptide (PMBN), which has no antibacterial action, was used to permeabilize the outer membrane. The addition of PMBN to Ps. aeruginosa NCTC 6749 markedly increased this organism's susceptibility to tea tree oil and to its normally inert hydrocarbons, p-cymene and gamma-terpinene.
Mann CM et al. The outer membrane of Pseudomonas aeruginosa NCTC 6749 contributes to its tolerance to the essential oil (tea tree oil). Letters in Applied Microbiology 30(4): 294-7. Apr 2000.

PERCIVAL, Food Science and Human Nutrition Department, The University of Florida, Gainesville, FL 32611, USA. ssp@gnv.ifas.ufl.edu reviewed (26 references) the medicinal use of echinacea.
Background: Echinacea (purple coneflower) is an herbal medicine that has been used for centuries, as a treatment for the common cold, coughs, bronchitis, upper respiratory infections, and some inflammatory conditions.
Discussion: Research on echinacea, including clinical trials, is limited and largely in German. More information is needed before a definitive statement about the efficacy of echinacea can be made. Future work needs to clearly identify the species of echinacea and distinguish between the efficacy of the different plant parts (roots versus upper plant parts). Many of the active compounds of echinacea have been identified. However, the mechanism of action, bioavailability, relative potency or synergistic effects of these active compounds are not known. Interpretation of existing literature suggests that echinacea should be used as a treatment for illness, not as a means for prevention of illness.
Conclusions: The authors conclude that the consensus of the studies reviewed in the article is that echinacea is indeed effective in reducing the duration and severity of symptoms, but that this effect is noted only with certain preparations of echinacea. Studies show that the plant and its active components affect the phagocytic immune system, but not the specifically acquired immune system.
Percival SS. Use of echinacea in medicine. Biochemical Pharmacology 60(2): 155-8. Jul 2000.

ROBY and colleagues, Department of Pharmacy, St Agnes Hospital, University of Maryland, Baltimore, USA conducted a clinical trial of the effect of St John's Wort on the activity of the metabolic enzyme CYP3A4.
Background: St John's Wort is a widely used herbal product. Our knowledge regarding its potential for drug interactions is required for responsible treatment of patients using St John's Wort. CYP3A4 is a metabolic enzyme implicated in most clinically significant drug-drug interactions. The aim of this study was to determine the in vivo effect of reagent-grade St John's Wort extract on CYP3A4 activity through evaluation of urinary 6-beta-hydroxycortisol/cortisol ratios.
Methods: Thirteen subjects (18 to 25 years old) participated in this open, multiple-dose, single-treatment before-after trial conducted in a university-based laboratory. Each subject was asked to ingest a 300-mg tablet of reagent-grade St John's Wort extract standardized to 0.3% hypericin three times a day for 14 days. Baseline and post-treatment CYP3A4 activity was assessed with the urinary 6-beta-hydroxycortisol/cortisol ratio after a 24-hour urine collection.
Results: The mean urinary 6-beta-hydroxycortisol/cortisol ratio significantly increased from 7.1 +/- 4.5 (baseline) to 13 +/- 4.9 (P = 0.003). The mean percentage increase was 114% +/- 95%, with a range from -25% to 259%. All but one subject had an increase in the ratio.
Conclusions: Treatment with St John's Wort for 14 days resulted in significant increases in the urinary 6-beta-hydroxycortisol/cortisol ratio. This finding suggests that St John's Wort is an inducer of CYP3A4.
Roby CA et al. St John's Wort: effect on CYP3A4 activity. Clinical Pharmacology and Therapeutics 67(5): 451-7. May 2000.

Comment: With the increasing use of herbal medicines, this study highlights the importance of studying potential interaction with conventional medicines.

SCHRADER, Praxis Klinische Arzneimittelforschung, Pohlheim, Germany conducted a clinical trial comparing the effects of St Johns Wort with fluoxetine on mild -moderate depression.
Background: There is an increasing amount of evidence for the efficacy of St Johns Wort in treating mild-moderate depression. This study compares St Johns Wort with the conventional anti-depressant fluoxetine.
Methods: Treatment with St John's wort extract tablets (hypericum Ze 117) and the commonly used slow serotonin re-uptake inhibitor (SSRI) fluoxetine was compared in patients with mild-moderate depression with entry Hamilton Depression Scale (HAM-D) (21-item) in the range 16-24, in a randomized, double-blind, parallel group comparison in 240 subjects; fluoxetine: 114 (48%), hypericum: 126 (52%).
Results: After 6 weeks' treatment, mean HAM-D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine (P < 0.09), while mean Clinical Global Impression (CGI) item I (severity) was significantly (P < 0.03) superior on hypericum, as was the responder rate (P = 0.005). Hypericum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. The commonest events on fluoxetine were agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness and erectile dysfunction (3% each), while on hypericum only GI disturbances (5%) had an incidence greater than 2%.
Conclusions: The authors concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population. Although hypericum may be superior in improving the responder rate, the main difference between the two treatments is safety. Hypericum was superior to fluoxetine in overall incidence of side-effects, number of patients with side-effects and the type of side-effect reported.
Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. International Clinical Psychopharmacology 15(2): 61-8. 2000.

Comment: This is another clinical trial to be added to the significant and growing evidence confirming the efficacy of St Johns Wort in mild-moderate depression and its comparability and possible superiority to conventional medicines.

Issue 55

ERNST and PITTLER, Department of Complementary Medicine, School of
Postgraduate Medicine and Health Sciences, University of Exeter UK performed
a systematic review of the evidence from randomized controlled trials
for or against the efficacy of ginger for nausea and vomiting.
Results: Six studies met all inclusion criteria and were reviewed. Three
were on postoperative nausea and vomiting; two of these suggested that
ginger was superior to placebo and equally effective as metoclopramide.
The pooled absolute risk reduction for the incidence of postoperative
nausea, however, indicated a non-significant difference between the
ginger and placebo groups for ginger: 1 g taken prior to the operation
(absolute risk reduction 0.052). One study was found for each of the
following conditions: seasickness, morning sickness and chemotherapy-induced
nausea. These studies collectively favoured ginger over placebo.
Ernst E and Pittler MH. Efficacy of ginger for nausea and vomiting:
a systematic review of randomized clinical trials. British Journal of
Anaesthesia 84(3): 367-71. Mar 2000.

BERBERINE (No author or institutional assignation) is a plant alkaloid
with a long history of medicine use in Ayurvedic and Chinese medicine.
Discussion: Berberine is present in Hydrastis canadensis (goldenseal),
Coptis chinensis (Coptis or goldenthread), Berberis aquifolium (Oregon
grape), Berberis vulgaris (barberry) and Berberis aristata (tree turmeric).
The berberine alkaloid is found in the roots, rhizomes and stem bark
of the plants. Berberine extracts and decoctions have demonstrated significant
antimicrobial activity against a variety of organisms including bacteria,
viruses, fungi, protozoans, helminths and chlamydia. The predominant
clinical uses of berberine currently include bacterial diarrhoea, intestinal
parasite infections and ocular trachoma infections.
Berberine. Alternative Medicine Review 5(2): 175-7. Apr 2000.

PARSONS and colleagues, Westmead Hospital, Australia studied the safety
and efficacy of raspberry leaf products consumed by a group of mothers
during their pregnancy, by comparison with a group of mothers who did
not.
Methods: The authors conducted a study using a retrospective observational
design. Recruited were 108 mothers who gave birth to their babies at
Westmead Hospital between January &#150; July 1998. 57 (52.8%) of the
women consumed raspberry leaf products and 51 (47.2%) were in the control
group.
Results: The findings suggest that the raspberry leaf herb can by consumed
by women during their pregnancy for the purpose for which it is taken,
namely to shorten labour with no identified side effects for the women
or their babies. The results also suggest that ingestion of the herb
might decrease the likelihood of pre and post-term gestation. An unexpected
finding in this study appears to indicate that women who ingest raspberry
leaf might be less likely to receive an artificial rupture of their
membranes, or require a caesarean section, forceps or vacuum birth than
the women in the control group.
ParsonsM et al. Raspberry leaf and its effect on labour: safety and
efficacy. Australian College of Midwives Incorporated Journal 12(3):
20-5. Sep 1999.

Issue 54

BIANCHI, Centro Orinetamento Educativo, Milano, Italy writes that clinical evaluation of modern phytotherapy is predominantly carried out today using meta-analysis.
Discussion: Meta-analyses generally reveal a marked contradiction of the results from individual clinical studies. Various explanations have been advanced for this anomaly: 1)that the products used are often of a different chemical and pharmacological nature; 2) that there is the problem of the "phytocomplex", in which all components of a medicinal plant, and not only its active ingredient may influence its therapeutic action. Generally only the active ingredient is standardized and the other ingredients end up by influencing the quality of the individual preparations in an unknown way; 3) the actual quality of the individual clinical studies and the possibility of taking the indications conveyed by traditional medicine into account when designing them.
Bianchi A. Phytotherapy between traditional medicine and alternative practices: how much safety and how much efficacy? Annali dell'Istituto Superiore di Sanita 35(4): 505-8. 1999.

KELMANSON and colleagues, Research Center for Plant Growth and Development, School of Botany and Zoology, University of Natal Pietermaritzburg, Scottsville, South Africa screened plants used in traditional Zulu medicine for antibacterial activity.
Methods: Aqueous, methanolic and ethyl acetate extracts of 14 plants used for the treatment of ailments of an infectious nature were screened for antibacterial activity.
Results: Most of the activity detected was against gram-positive bacteria. Tuber bark extracts of Dioscorea sylvatica had activity against gram-negative Escherichia coli and extracts of Dioscorea dregeana, Cheilanthes viridis and Vernonia colorata were active against Pseudomonas aeruginosa. The highest antibacterial activity was found in extracts of C.viridis, D. dregeana, D. silvatica, Melianthus comosus and V. colorata. Generally, methanolic extracts showed higher antibacterial activity then aqueous and ethyl acetate extracts.
Conclusions: South African plants used in traditional Zulu medicine showed antibacterial activity against gram-negative and gram-positive bacteria.
Kelmanson JE et al. Zulu medicinal plants with antibacterial activity. Journal of Ethnopharmacology 69(3): 241-6. Mar 2000.

Issue 53

PITTLER and ERNST, Department of complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, United Kingdom. M.H. Pittler@exeter.ac.uk conducted a systematic review and meta-analysis to assess the evidence for and against the efficacy of kava extract as a symptomatic treatment for anxiety.
Methods: The authors conducted systematic and unrestricted literature searches of MEDLINE, EMBASE, BIOSIS, AMED, CISOM and the Cochrane Library to June 1998 using the search terms kava, kawa, kavain, Piper methysticum and Rauschpfeffer (German for Piper methysticum). All publications were blinded prior to assessment by a person not involved in the study, and data were extracted in a standardized, predefined manner independently by the two reviewers. The methodologic quality of all the trials were assessed.
Results: All seven reviewed trials suggested superiority of kava extract over placebo; the meta-analysis of three trials suggested a significant difference in the reduction of the total score on the Hamilton Rating Scale for Anxiety in favour of kava extract.
Conclusions: The data imply that kava extract is superior to placebo in the symptomatic treatment for anxiety; hence kava extract should be considered as a valid treatment for anxiety.
Pittler MH and Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. Journal of Clinical Psychopharmacology 20(1): 84-9. Feb 2000.

MARKOWITZ and colleagues, Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston 29425 USA. markowij@musc.edu studied the effects of St John’s wort (Hypericum perforatum) upon the activity of cytochrome P-450 (CYP) 2D6 and 3A4.
Methods: Probe substrates dextromethorphan (2D6 activity) and alprazolam (3A4 activity) were taken orally with and without the co-administration of St John’s wort in seven normal volunteers. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic rations (DMRs) determined. Validated HPLC methods were used to quantify all compounds of interest.
Results: No statistically significant differences were discovered in any estimated pharmacokinetic parameter for alprazolam or DMRs.
Conclusions: These results suggest that St John’s wort when taken at recommended doses for depression, is unlikely to inhibit CYP 2D6 or CYP 3A4 activity.
Markowitz JS et al. Effect of St John’s wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers. Life Sciences 66(9): PL133-9. 21 Jan 2000.

Issue 52

GASTER and HOLROYD, Department of Medicine, University of Washington, Seattle, USA barakg@u.washington.edu conducted a systematic review (40 references) of the English language literature regarding the efficacy, safety and availability of St John's wort in the treatment of depression.
Methods: The authors selected studies using randomized, controlled, double-blind trials; methodological quality was assessed using a standardized checklist, and data regarding pharmacology, cost, regulation and safety were extracted. 8 studies were identified and found to be of generally good methodological quality. These studies provided data suggesting that St John's wort is more effective than placebo in the treatment of mild to moderate depression. The absolute increased response rate with the use of St John's wort ranged from 23% to 55% higher than with placebo, and 6% to 18% lower compared with tricyclic antidepressants.
Conclusions: More data are required to assess both its use in severe depression and its efficacy compared with other antidepressants. Side effect rates were low. St John's wort is currently largely unregulated; however the Food and Drug Administration is reviewing plans to tighten regulations.
Gaster B and Holroyd J. St John's wort for depression: a systematic review. Archives of Internal Medicine 160(2): 152-6. 24 Jan 2000.

KLEPSER and colleagues, Division of Clinical and Administrative Pharmacy, University of Iowa College of Pharmacy, Iowa City 52242 USA evaluated the demographics and beliefs regarding safety and efficacy of herbal therapy among people in Iowa, and assessed their willingness to discuss the use of these products with health care providers.
Methods: The authors distributed 1300 surveys to two random samples: patients attending eight clinics, and to residents of the state via the post. Data were categorized according to herb use and compared between users and nonusers. The response rate was 61% (794 people), with 41.6% of respondents reporting herb use. Users of herbs were predominantly women of higher education, with a high use of prescription drugs. Users rated safety and efficacy of herbs higher than nonusers; however both groups believed that health care providers should be more aware of herbal use and should provide this information.
Klepser TB et al. Assessment of patients' perceptions and beliefs regarding herbal therapies. Pharmacotherapy 20(1): 83-7. Jan 2000.

ERNST, Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK. E.Ernst@exeter.ac.uk conducted an overview of systematic reviews of herbal treatment for conditions common in elderly individuals.
Results: Hypericum perforatum (St John's Wort) is well-tolerated and effective for mild to moderate depression. Valeriana officinalis (valerian) has not been shown beyond reasonable doubt to be effective for insomnia. There is relatively compelling evidence that Ginkgo biloba (ginkgo) is effective in delaying the clinical course of dementias. It has been well documented that Aesculus hippocastanum (horse chestnut) seed extracts relieve subjective symptoms and reduce objective signs of chronic venous insufficiency. Serenoa repens (saw palmetto) is effective in improving symptoms of benign prostatic hyperplasia. Ohimbine has been shown to be effective for erectile dysfunction.
Conclusions: Various plant-based medicines are useful additions to the therapeutic repertoire in the treatment of common conditions in the elderly. There are, however, several remaining uncertainties which prevent unreserved recommendations.
Ernst E. Herbal medications for common ailments in the elderly. Drugs and Ageing 15(6): 423-8. Dec 1999.

FISHER and colleagues, United States Air Force School of Aerospace Medicine, Brooks Air Fore Base, TX 78235 USA. charles.fisher@mirage.brooks.af.mil conducted a study and review (43 references) to identify the botanical preparations of potential risk to the aviator and aviation safety. The authors attempt to ascertain whether pilots are using dietary supplements despite extensive educational efforts discouraging over-the-counter medication use.
Background: Herbal medicines may be used by nearly 20% of the adult population. It is presumed that pilots use herbal medicines also, the actual degree of use is unknown. Although such (herbal) substances may provide health benefits, they may also carry risk. Military and civilian aviators are not currently required to disclose such use, nor are examiners obliged to enquire or counsel pilots about them. The authors review the trends in post-mortem toxicological samples suggesting botanical preparation use and suggesting methods for determining suitability for their use by pilots.
Methods: The toxicological test results from 3177 mishap pilots performed at the Civil Aeromedical Institute from 1989-97 were studied for the presence of substances suggesting botanical preparation use. The prevalence of positive test results for ephedrine among mishap pilots was compared with the prevalence of tests positive for chemically and biologically similar non-botanical substances among mishap pilots. The authors reviewed the literature to identify substances posing possible risk to pilot health of aviation safety.
Results: Ephedrine was found to be the only substance routinely screened on toxicological specimens which was suitable for association with botanical substance use. Percent of specimens positive for ephedrine increased three- to four-fold while percent for specimens positive for similar non-botanical substances decreased overall. The literature revealed sufficient evidence that a number of open market botanical agents are capable of causing incapacitation by cardiovascular or neuropsychiatric mechanisms, yet are legally permitted for use by pilots.
Conclusions: Pilots are using botanical products with increasing frequency; many of those substances may pose significant risk of incapacitation, altered sensorium or adverse health effects. The flight surgeon must be diligent in eliciting a history of use and assisting pilots to minimize personal risk and risks to flight safety. A rational approach to assessing risk is presented.
Fisher CR Jr, and Veronneau SJ. Herbal preparations: a primer for the aeromedical physician. Aviation, Space and Environmental Medicine 71(1): 45-60. Jan 2000.

Comments: Alison Denham, Research Director, NIMH There is abuse of OTC products containing ephedrine from Ephedra sinensisin in the USA. The Texas Poison Control Network received 500 reports of symptoms from such products between December 1993 and September 1995. Used in slimming and "natural stimulant" products, ephedrine stimulates the sympathetic nervous system. Symptoms included tremor, insomnia, dizziness, fatigue and vomiting, with 8 deaths from heart attack or stroke. In three deaths, the recommended dose had not been exceeded. It is not surprising that air pilots might take such products to remain alert; ephedrine was used by pilots in WWII to remain alert on long missions.
In Britain, the legal use of Ephedra sinica is limited by the Medicines Act 1968 to herbal practitioners. A survey of the National Institute of Medical Herbalists (NIMH) in 1998 showed that practitioners use it at low doses mainly for asthma and hayfever, which are regulated by the Medicines Act. Reactions of dry mouth, constipation and nervousness all cleared on stopping Ephedra sinica.
This is a herb which should not be available over the counter and should be restricted to usage at limited dosage by herbal practitioners.

Issue 47

REHMAN and colleagues, Department of Internal Medicine, Veterans Affairs Medical Center and University of California, San Diego 92161 USA write that little is known about whether treatment with certain medicinal plants can enhance antigen-specific immunity. The authors studied the immune effects of Echinacea angustifolia and Goldenseal (Hydrastis canadensis).
Methods: The authors investigated, using the novel antigen keyhole limpet hemocyanin (KLH) injected into rats, the antigen-specific in vivo immunomodulatory potential of continuous treatment with Echinacea and Goldenseal root extract for a period of 6 weeks.
Results: The Echinacea-treated group showed a significant augmentation of their primary and secondary IgG antigen response; the Goldenseal-treated group showed an increase in the primary IgM response during the first 2 weeks of treatment.
Conclusions: These data suggest that medicinal plants such as Echinacea and Goldenseal may enhance immune function by increasing antigen-specific immunoglobulin production.
Rehman J et al. Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis. Immunology Letters 68(2-3): 391-5. 1 Jun 1999.

CHANG, Pharmanex Inc., Simi Valley California 93065 USA. jchang@pharmanex.com writes that in the United States traditional Chinese medicines (TCM) are sold as dietary supplements, defined under The dietary Supplement Health and Education Act (DSHEA). The author discusses issues regarding the characterisation of the pharmacological activity of TCM herb and the development of a standardised herbal extract.
Discussion: The DSHEA legislation permits structure and function claims, but no disease claims. The narrow definition of the legislation poses difficulties in designing appropriate clinical studies to provide data for structure and function claim substantiation. The process of melding Chinese herbal medicines into the dietary supplement category is complex; it is frequently not recognised that TCM favours an amalgamation of several herbs to generate the putative clinical effect. Due to this historical multiherb approach, the reliance on retrospective data to support the potential health benefits of an herb extract has severe limitations. Another approach to safe and efficacious herbal products is to develop a standardised herbal extract. The author discusses a research-based strategy which may be suitable for validating, in part, the putative health benefits of TCM.
Chang J. Scientific evaluation of traditional Chinese medicine under DSHEA: a conundrum. Dietary Supplement Health and Education Act. The Journal of Alternative and Complementary Medicine 5(2): 181-9. Apr 1999.

Issue 46

BALES and colleagues, Department of Surgery, University of Chicago Pritzker School of Medicine, Illinois USA conducted a survey to assess awareness and use of phytotherapeutic agents for the treatment of urinary tract symptoms (LUTS).
Methods: The authors conducted a survey of 1280 patients presenting to the University of Chicago Hospitals urology clinic. The questionnaire related to age, race, educational level and use of prescription and non-prescription medications for urinary symptoms.
Results: 1264 patients (98.8%) correctly completed the questionnaire. Individuals in the 51-60 year range showed the greatest percentage of use of botanical agents. Whites were almost twice as likely as African Americans to use medicinal botanicals and men with college or graduate school degrees were 1.5 times as likely to use medicinal botanicals to treat LUTS. Greater than 50% of men using phytotherapeutic drugs were also taking prescription medications for their urinary symptoms.
Conclusions: There is significant use of phytotherapeutic agents in men with LUTS, with variability in their use between patient groups. Physicians need to understand the use of mechanisms of botanical medicines in order to best advise and treat their patients.
Bales GT et al Phytotherapeutic agents in the treatment of lower urinary tract symptoms: a demographic analysis of awareness and use at the University of Chicago. Urology 54(1): 86-9 July 1999.

GRAY and FLATT, School of Biomedical Sciences, University of Ulster, Coleraine, UK write that Coriandrum sativum (coriander) has been documented as a traditional treatment for diabetes. The authors conducted a study to investigate the antihyperglycaemic and insulin-modulating properties of coriander.
Methods: The authors incorporated coriander into the diet (62.5g/kg) and drinking water (2.5g/l) of streptozotocin-diabetic mice.
Results: Coriander incorporated into the diet and drinking water reduced hyperglycaemia. An aqueous extract of coriander (1 mg/ml) increased 2-deoxyglucose transport (1.6-fold), glucose oxidation (1.4-fold) and glucose incorporation into glycogen (1.7-fold) of isolated murine abdominal muscle comparable with 10-8 M-insulin. In acute 20 minute tests, aqueous extract of coriander evoked a stepwise 1.3-5.7-fold stimulation of insulin secretion, which was abolished by 0.5 mM-diazoxide. Prior exposure to the extract did not change subsequent stimulation of insulin secretion by 10 mM-L-alanine, and thereby negated an effect caused by detrimental cell damage. The extract’s effect was potentiated by 16.7 mM-glucose and 10 mM-L-alanine but not by 1 mM-3-isobutyl-1-methylxanthine. Insulin secretion was further enhanced by the presence of extract. The extract’s activity was heat stable, acetone soluble and not altered by overnight exposure to acid or dialysis. Its activity was reduced by overnight exposure to alkali. Sequential extraction with solvents revealed insulin-releasing activity in hexane and water fractions which indicated a possible cumulative effect of more than one extract constituent.
Conclusions: These results demonstrate the presence of antihyperglycaemic, insulin-releasing and insulin-like activity in Coriandrum sativum.
Gray AM and Flatt PR Insulin-releasing and insulin-like activity of the traditional anti-diabetic plant Coriandrum sativum (coriander). British Journal of Nutrition 81(3) 203-9. Mar 1999.

Issue 37

DE SMET, Pharmaceutical Care Unit, Scientific Institute Dutch Pharmacists, The Hague, The Netherlands. writes that many of our present medicines are derived directly or indirectly from higher plants. The author has extensively reviewed the literature (525 references!) regarding the role of plant medicines in healthcare.
Results: While certain classic plant drugs have lost ground to synthetic competitors, others have recently assumed a more prominent investigational status. Also, several novel plant-derived substances have entered into Western drug markets. Rewarding progress from clinical plant-based research has occurred, particularly with cancer (taxoids and camptothecins) and malarial (artemisinin) compounds.
Discussion: In addition to purified plant-derived drugs, there is a large market for crude herbal medicines. Research in natural products can be guided by ethnopharmacological knowledge, which can significant contributions to drug innovation by providing novel chemical structures and/or mechanisms of action. Ultimately, however, both plant-derived drugs and crude herbal medicines need to take the same pharmacoeconomic hurdle as new synthetic pharmaceuticals.
De Smet PA. The role of plant-derived drugs and herbal medicines in healthcare. Drugs 54(6): 801-40. Dec 1997.

COMMENTS: Given the clinical importance of many plant and herbal medicines, it is indeed highly questionable that the Medicines Control Agency may soon be granted the power to remove many of these products from the shelves of our health food stores (please see pages 6-7 of this issue).

Issue 36

BORCHERS and colleagues, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis 95616 USA write that demand for and scientific interest in many aspects of complementary medicine, particularly medicinal botanicals has increased considerably in recent years. Chinese herbal medicines and their Japanese counterparts – Kampo – are those with the longest tradition and for which the most extensive data are available.
Methods: The authors review (54 references) representative examples of studies researching the effects of certain traditional Chinese medicines upon various aspects of the immune response. The author cites in vitro and in vivo studies, the latter including animal and human clinical trial data.
Results: The review demonstrates that considerable research has focused upon the specific benefits of Chinese herbal medicines; however, many fewer studies exist which study the mechanisms whereby they exert their immunomodulatory actions. The limited number of mechanistic data presented in the review demonstrate that a number of mechanisms are likely to be involved in the various actions of even a single medicine.
Conclusions: The elucidation of these mechanisms will ultimately provide the scientific basis to establish the safety and efficacy of Chinese herbal medicines and ultimately all forms of medicinal botanicals.
Borchers AT et al. Complementary medicine: a review of immunomodulatory effects of Chinese herbal medicines. Am J Clin Nutr 66(6): 1303-12. Dec 1997.

SHAW and colleagues, Medical Toxicology Unit, Guy's and St Thomas' Hospital Trust, London, UK write that the Medical Toxicology Unit (MTU) at Guys' Hospital has been evaluating the toxicological problems associated with the use of traditional and herbal remedies and dietary supplements.
Methods: Assessments were performed by evaluating reports to the National Poisons Information Service London (NPISL), which supplies emergency information to medical professionals. Relevant telephone enquiries to NPISL were identified and further case details obtained through follow-up questionnaire, clinical consultation, toxicological analysis of samples from patients and/or products and botanical identification of plant material.
Results: Of 1297 symptomatic enquiries evaluated, there was a possible/confirmed association in 785 cases. Case series were identified substantiating previous reports, including liver problems following the use of Chinese herbal medicines used for skin disorders, allergic reactions to royal jelly and propolis and heavy metal poisoning from remedies from the Indian subcontinent.
Discussion: Although the overall risk to public health appears to be low, certain types of traditional remedies have been associated with some potentially serious adverse effects. In view of the extent of the use of herbal remedies and food supplements, the authors consider a comprehensive surveillance system to monitor adverse health effects of these products essential. They stipulate that surveillance of a large population is required in order to complete the complex task of identifying the uncommon and unpredictable adverse effects which are potentially serious. The Medicines Control Agency in the UK responded to the MTU report and recognised the need for vigilance and incorporated adverse reactions reporting on unlicensed herbal remedies into their drug reaction monitoring function. The authors further suggest that as an additional step to safeguard patients/consumers, an effective single regulatory system is needed to ensure the safety and quality of all herbal remedies and food supplements available in the UK.
Shaw D et al. Traditional remedies and food supplements. A 5-year toxicological study (1991-1995). Drug Saf 17(5): 342-56. Nov 1997.

COMMENTS: Sadly, it is the relatively small number of adverse reactions occurring to herbal medicines and nutritional supplements which often get headlined in the television and print media and which ultimately could lead to many of our most cherished medicines becoming controlled or available only on prescription. It is important that practitioners and consumers not be complacent about adverse reactions, but also remain vigilant to protect the free availability of nutritional and herbal supplements.

STERN, (affiliation not supplied), reports the treatment of 2 cases of hepatitis C using herbal medicine and nutritional supplements.
Methods: The selection of medicines was based upon biomedical findings as well as traditional Chinese medical diagnosis. The course of each patient's illness is presented both subjectively and objectively with blood values and traditional Chinese medicine analysis as parameters. The explanation and/or citations are provided for each medicinal used.
Results: Both patients improved during the course of treatment. Subjective signs and symptoms, particularly fatigue, and liver enzyme levels all improved.
Stern E. Two cases of hepatitis C treated with herbs and supplements. J Altern Complement Med 3(1): 77-82. Spring 1997.