Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Systematic reviews of complementary therapies – an annotated bibliography. Part 2: Herbal medicine

  • Klaus Linde1, 2Email author,
  • Gerben ter Riet3, 4,
  • Maria Hondras5,
  • Andrew Vickers6,
  • Reinhard Saller7 and
  • Dieter Melchart1
BMC Complementary and Alternative MedicineBMC series ¿ open, inclusive and trusted20011:5

DOI: 10.1186/1472-6882-1-5

Received: 22 March 2001

Accepted: 20 July 2001

Published: 20 July 2001

Abstract

Background

Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with herbal medicine. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of herbal medicines; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pre-tested form and summarized descriptively.

Results

From a total of 79 potentially relevant reviews pre-selected in the screening process 58 met the inclusion criteria. Thirty of the reports reviewed ginkgo (for dementia, intermittent claudication, tinnitus, and macular degeneration), hypericum (for depression) or garlic preparations (for cardiovascular risk factors and lower limb atherosclerosis). The quality of primary studies was criticized in the majority of the reviews. Most reviews judged the available evidence as promising but definitive conclusions were rarely possible.

Conclusions

Systematic reviews are available on a broad range of herbal preparations prescribed for defined conditions. There is very little evidence on the effectiveness of herbalism as practised by specialist herbalists who combine herbs and use unconventional diagnosis.

Introduction

In this second part of our series on systematic reviews in complementary therapies we report our findings on herbal medicines. Herbal medicines (defined as preparations derived from plants and fungi, for example by alcoholic extraction or decoction, used to prevent and treat diseases) are an essential part of traditional medicine in almost any culture [1]. In industrialized countries herbal drugs and supplements are an important market. Some countries like Germany have a long tradition in the use of herbal preparations marketed as drugs and figures for prescriptions and sales are stable or slightly declining [2]. In the US and the UK herbal medicinal products are marketed as "food supplements" or "botanical medicines". In recent years sales of such products have been increasing strongly in these countries [3, 4]. In the Third World herbs are mainly used by traditional healers [5].

Methods

A detailed description of the methods used in this review of reviews is given in the first part of this series [6]. For searches in Medline 50 single plant names and the 'exploded' term 'medicinal plants' were combined with the standard search strategy for systematic reviews. As a specific intervention-related inclusion criterion we required that reports reviewed prospective (not necessarily controlled) clinical trials of substances extracted from plants in humans. Reviews dealing with single substances (e.g., artemisin derivatives) derived from plants were excluded on the grounds that such agents are comparable to conventional drugs. Disease-oriented reviews including a variety of interventions were included only if they reviewed at least 4 herbal medicine trials.

Results

From a total of 79 potentially relevant reviews preselected in the literature screening process, 58 (published in 65 papers) met the inclusion criteria [771]. Eleven reports were not truly systematic reviews (not meeting inclusion criterion 2) [7282], 5 dealt with isolated substances of plant origin [8387] and 4 were excluded for other reasons (one disease- focused review with less than 4 herbal medicine trials [88], one review not on preventative or therapeutic use [89], two reviews not truly herbal medicine [90, 91]).

More than half of the reports reviewed gingko, hypericum or garlic preparations. No less than 13 systematic reviews dealed with ginkgo (Ginkgo biloba) extracts (see table 1). Seven of these reviewed trials (total number of trials covered in any of the reviews 15) in patients with intermittent claudication [713]. Most of these reviews concluded that ginkgo extracts were significantly more effective than placebo in increasing measures like walking distance but the clinical relevance of the effects was felt to be moderate by some reviewers. The five reviews dealing with dementia and cerebral insufficiency (total number of trials included about 50) all draw positive conclusions [1317]. However, many of the older trials were in patients with minor cognitive impairment and more evidence is needed to decide whether ginkgo extracts have clinically relevant beneficial effects in more severe forms of dementia. Finally, one review found that ginkgo extracts might be effective in the treatment of tinnitus [18] and another found insufficient evidence for efficacy in patients with macular degeneration [19].
Table 1

Systematic reviews of clinical trials of ginkgo biloba extracts

     

Features

  

Author Year

Indication

Intervention

Comparisons

Studies

1/2/3/

Results

Author's Conclusion

     

4/5

  

Ginkgo ( Ginkgo biloba )

Pittler 2000

intermittent

ginkgo

placebo

8 RCT

y/y/y/

Increase of pain-free walking

Evidence for a modest benefit of

[7]

claudication

   

y/y

distance over placebo after 12

uncertain clinical relevance

      

or 24 weeks 34 m (95%CI 26–

 
      

43 m)

 

Moher 2000

intermittent

ginkgo*

placebo

5 RCT

y/y/y/

Increase of pain-free walking

Inconsistent results from the few

[8]

claudication

   

n/y

distance over placebo after 24

available small studies do not

      

weeks 32 m (95%CI 14–50 m)

allow firm conclusions

Ernst 96 [9]

intermittent

ginkgo

placebo,

10

p/ p/ n/

Most studies low quality.

Available evidence promising but

 

claudication

extract

other drugs

RCT/CCT

n/n

Increase of walking distance

further high quality research

  

EGb761

   

compared to placebo 24 to 160

needed

      

m. At least similar

 
      

effectiveness compared to

 
      

other drugs.

 

Schneider 92

intermittent

ginkgo

placebo,

7 RCT/CCT

?/n/n/

mean effect size d = 0.75

Effectiveness over placebo clearly

[10]

claudication

 

other

(vs. plac.), 2

y/y

(95%CI 0.44–1.07) over

shown

   

treatment

RCT/CCT

 

placebo

 
    

(other)

   

Letzel 92

intermittent

ginkgo

ginkgo vs.

5 RCT

?/p/n/

Pooled increase of walking

Ginkgo extract EGb761 more

[11]

claudication

extract

plac.,

ginkgo

y/y

distance: 45% over placebo for

effective than placebo and

  

EGb 761

pentoxifyllin

9 RCT

 

gingko and 57% for

similarly effective as pentoxifyllin

   

vs. plac.

pentoxifyllin

 

pentoxifyllin

 

Kleijnen 91

intermittent

ginkgo

ginkgo vs.

15

y/y/y/

Many trials low quality. All trials

Ginkgo seems effective for

[12]

claudication

 

plac.,

RCT/CCT

n/n

with positive results. Evidence

intermittent claudication but further

   

pentoxifyllin

(ginkgo), 5

 

similar as for pentoxifyllin

high quality studies are needed

   

vs. placebo

RCT/CCT

   
    

pentoxif.

   

Weiss 91

cerebral ins.,

ginkgo

placebo

17RCT/CCT

?/p/p/

10 of 12 interpretable trials on

Effectiveness for both conditions

[13]

intermittent

extract

 

(cerebral

n/n

cerebral insufficieny and all 4

biometrically shown

 

claudication

EGb761

 

ins.), 8

 

interpretable trials on

 
    

RCT/CCT

 

intermittent claudication with

 
      

significant positive results

 

Ernst 99 [14]

dementia

ginkgo

placebo

9 RCT

y/y/y/

Results collectively suggest

Encouraging findings warranting

     

y/n

that ginkgo is more effective for

large scale trials

      

dementia than placebo

 

Oken 98 [15]

Alzheimer

ginkgo

placebo

4 RCT

y/y/n/

Significant effect over placebo

Clinical relevance of the observed

 

dementia

   

y/y

for cognitive function (Hedges

effects has to be confirmed in

      

g= 0.41, 95%CI 0.22–0.61)

further research

Hopfenmüller

cerebral

ginkgo

placebo

10 RCT, 1

n/ n/ n/

Global response (based on

Ginkgo extract superior to placebo

94 [16]

insufficiency

extract LI

 

CCT

y/y

symptom scores): OR 1.98

 
  

1370

   

(95%C11.39–2.57) in favour of

 
      

Ginkgo

 

Kleijnen 92

cerebral

ginkgo

ginkgo vs.

40 RCT/

y/y/y/

Many trials low quality. Virtually

Ginkgo seems effective for

[17]

insufficiency

 

plac.

CCT

n/n

all trials reported positive

cerebral insufficiency but further

   

hydergine

(ginkgo), 4

 

results. Evidence similar as for

high quality studies are needed

   

vs. plac.

RCT/CCT

 

hydergine

 
    

(hydergine)

   

Ernst 99 [18]

tinnitus

ginkgo

placebo,

5 RCT

y/y/y/

3 trials favour ginkgo over

Results suggest that extracts of

   

other

 

y/n

placebo, 1 no difference, in one

ginkgo biloba are effective in

   

treatment (1

  

trial ginkgo better than another

treating tinnitus

   

trial)

  

treatment

 

Evans 2000

macular

ginkgo

placebo

1 RCT

y/y/y/

one small trial reporting

Insufficient evidence to

[19]

degeneration

   

y/-

improvement

recommend ginkgo for age-related

       

macular degeneration

Features: 1 = comprehensive search, 2 = explicit inclusion criteria, 3 = formal quality assessment, 4 = summary of results for each included study, 5 = meta-analysis; y = yes, p = partly, n = no, - = not applicable, ? = unclear review on all pharmacologic treatments for the respective condition RCT = randomized controlled trials, CCT = non-randomized controlled trials, CS = cohort studies, UCS = uncontrolled studies; OR = odds ratio, RR = rate ratio

The effectiveness of St. John's wort (Hypericum perforatum) extracts in depression was investigated in nine reviews [2030] (total number of trials covered 29; see table 2). Mainly due to slight differences in the inclusion criteria (for example, restriction to trials with a minimum of 6 weeks observation or with a minimum quality score) the respective study collections differed to a considerable amount. However, the conclusions were very similar. Hypericum extracts have been shown to be superior to placebo in mild to moderate depressive disorders. There is growing evidence that hypericum is as effective as other antidepressants for mild to moderate depression and causes fewer side effects but further trials are still needed to establish long-term effectiveness and safety.
Table 2

Systematic reviews of clinical trials of hypericum and garlic preparations

     

Features

  

Author

Indication

Intervention

Comparisons

Studies

1/2/3/

Results

Author's Conclusion

Year

    

4/5

  

St John's wort ( Hypericum perforatum )

Gaster

depression

hypericum

placebo and

8 RCT

p/y/p/

4 placebo-controlled trials with

Data suggest that hypericum is

2000 [20]

  

antidepressants

 

y/n

positive results, in 4 trials

superior to placebo, insuffcient

      

standard antidepr. tended to be

evidence re equivalence with

      

slightly better

antidepressants

Williams

depression

hypericum

placebo and

14 RCT

y/y/n/

Treatment response: RR 1.9

Data suggest that hypericum is

2000 &

 

(and other

antidepressants

 

y/y

(95%C11.2–2.8) vs. placebo and

superior to placebo, insuffcient

Mulrow 98

 

drugs)

   

1.2 (1.0–1.4) vs. antidepressants

evidence re equivalence with

[21, 22]

      

antidepressants

Kim 99 [23]

depression

hypericum

placebo and

6 RCT

p/y/y/

Treatment response: RR 1.48

Hypericum more effective than

   

antidepressants

 

y/y

(95%C11.03–1.92) vs. placebo

placebo and similarly effective as

      

and 0.98 (0.67–1.28) vs.

low dose antidepressants; quality

      

antidepressants

problems

Stevinson

depression

hypericum

placebo and

6 RCT

y/y/y/

Only trials published after Linde

Data confirm findings of earlier

99 [24]

  

antidepressants

 

y/n

96; trials show effects better

trials, but still insuff. evidence to

      

than placebo/similar to

assess equivalence with

      

antidepressants

antidepressants

Linde 98 &

depression

hypericum

placebo and

27 RCT

y/y/y/

Treatment response: RR 2.47

Hypericum more effective than

96 [25, 26]

  

antidepressants

 

y/y

(95%C11.69–3.61) vs. placebo

placebo. Inadequate evidence to

      

and 1.01 (0.87–1.16) vs.

assess equivalence with

      

antidepressants

antidepressants

Volz 97

depression

hypericum

placebo and

15

p/p/n/

Most placebo-controlled trials

A therapy with hypericum of mild

[27]

  

antidepressants

RCT/CCT

n/n

positive; similarly effective as

and moderate depression can be

      

(not adequately dosed)

attempted. Further studies needed

      

antidepressants

 

Ernst 95

depression

hypericum

placebo and

11 RCT

y/y/y/

Most of 8 placebo-controlled

Hypericum is superior to placebo

[28]

  

antidepressants

 

y/n

trials positive. 3 trials against

and seems equally effective as

      

standard medication with similar

standard medication

      

effects

 

Volz 2000

mild to

hypericum

fluoxetine

17+9

n/y/n/

No direct comparison of

Response rates are similar;

[29]

mod.

  

CCT

y/n

hypericum and fluoxetine

findings difficult to interpret

 

depression

    

available. Mean depression

because of the indirect comparison

      

score (HAMD) reduction in

 
      

hypericum trials 53%, in

 
      

fluoxetine trials 55%

 

Friede 98

anxiety in

hypericum

placebo,

8 RCT

?/y/y/

Trials collectively show reduction

Hypericum is effective for

[30]

depressed

 

amitriptyline

 

y/n

of anxiety symptoms over

depressed patients with anxiety

 

p.

    

placebo. Only 1 trial vs

 
      

amitriptyline

 

Garlic ( Allium sativum )

Lawrence

cardiovasc.

garlic

mainly placebo;

45 RCT

y/y/y/

37 trials consistently show small

Insufficient data to draw conclusion

2000 [31]

risk factors

 

no & other

 

y/y

short-term effects over placebo

regarding clinical cardiovascular

   

treatment

  

for cholesterol reduction. No

outcomes. Garlic preparations may

      

consistent effects on blood

have small, positive, short-term

      

pressure, promising effects re

effects on lipids

      

platelet aggregation and

 
      

fibrionolytic activity

 

Stevinson

hyperchol-

garlic

placebo

13 RCT

y/y/y/

Pooled total cholesterol

Available data suggest that garlic is

2000 [32]

esterolemia

   

y/y

reduction over placebo 0.41

superior to placebo. The size of the

      

(95% Cl -0.66 to -0.15) mmol/l;

effect is modest. The use of garlic

      

when analysis restricted to high

for hyperchol. is therefore of

      

quality trials 0.11 (-0.30 to 0.08)

questionable value

Silagy 94 &

cholesterol

garlic

placebo

16 RCT

y/p/y/

Pooled cholesterol reduction

Meta-analysis suggests positive

Neil 96

lowering

   

y/y

over placebo 0.65 (95% Cl 0.53–

effects but reviewers are sceptic

[33, 34]

     

0.76) mmol/l

(low quality; own replication

       

negative)

Warshafsky

cholesterol

garlic

placebo

5 RCT

p/y/y/

Pooled cholesterol reduction

Available evidence supports the

93 [35]

lowering

   

y/y

over placebo 0.59 (95%Cl 0.44–

use of garlic as one modality to

      

0.74) mmol/l

decrease cholesterol levels

Silagy 94

lowering

dried garlic

placebo, other

8 RCT

y/p/y/

Pooled reduction over placebo:

Garlic maybe of some clinical use

[36]

blood

(Kwai)

treatment

 

y/y

SBP 7.7 (95% Cl 4.3–11.0), DBP

in subjects with mild hypertension.

 

press.

    

5.0 (2.9–7.1) mm Hg

Further research needed

Kleijnen 91

cardiovasc.

garlic

placebo

18

p/p/y/

Most studies with shortcomings.

No clear conclusion drawn

[37]

risk factors

supplements

 

RCT/CCT

y/n

The majority of trials with pos.

 
      

results but inconsistent effect

 
      

sizes

 

Kleijnen 89

cardiovasc.

garlic &

unclear

10 RCT,

y/p/n/

All trials with severe

Inadequate evidence to justify

[38]

risk factors

onions

 

8 CCT

y/n

shortcomings. Fresh garlic with

supplementation, further research

      

beneficial effcts, onions and

needed

      

commercially available

 
      

supplements yielded

 
      

contradictory results

 

Jepson 97

lower limb

garlic

placebo

1 RCT

y/y/y/

Walking distance not

Insufficient evidence

[39]

atheroscler.

   

y/-

significantly different between

 
      

groups

 

legend see table 1

Eight reviews have been performed on garlic (Allium sativum) for cardiovascular risk factors [3138] (total number of trials covered about 50) and lower limb atherosclerosis [39] (see table 2). A modest short-term effect over placebo on lipid-lowering seems to be established but the clinical relevance of these effects is uncertain. Data from randomised trials on cardiovascular mortality are not available. Effects on blood pressure seem to be at best minor. The available results on fibrinolytic activity and platelet aggregation are promising but insufficient to draw clear conclusions. A specific problem in research on garlic is the great variety of garlic preparations used: the exact content of bioactive ingredients in these is often unclear.

Three reviews (covering a total of about 30 trials) have been performed on preparations containing extracts of Echinacea (Echinacea purpurea, pallida or angustifolia), two of which by the same study group [4043]. The results suggest that Echinacea preparations may have some beneficial effects mainly in the early treatment of common colds. Similar to garlic a major problem is the high variaton of bioactive compounds between different Echinacea preparations. Cranberries (Vaccinium macrocarpon) for urinary tract infections [44, 45], mistletoe (Viscum album) for cancer [4648], peppermint (Mentha piperita) oil for irritable bowel syndromes [49, 50] and saw palmetto (Serenoa repens) for benign prostate hyperplasia [5153] have each been subject to two reviews. For saw palmetto there is good evidence for efficacy over placebo while for the other three the data are inconclusive (see table 3).
Table 3

Systematic reviews of clinical trials of herbal medicines (at least 2 reviews per herb)

     

Features

  

Author

Indication

Intervention

Comparisons

Studies

1/2/3/

Results

Author's Conclusion

Year

    

4/5

  

Echinacea ( Echinacea purpurea, angustifolia and pallida )

Barrett

upper resp.

echinacea

placebo

13RCT

y/p/y/

Overall quality modest. All 4

Echinacea may be beneficial for

99 [40]

infections

(incl.

  

y/n

prevention studies show only

early treatment of acute upper

  

combinations)

   

minor trends, 8 of 9 treatment

respiratory infections; little evidence

      

studies with generally positive

to support the prolonged use for

      

results

prevention

Melchart

common

echinacea

placebo, no

16 RCT

y/y/y/

Minor effects in prevention and

Echinacea extract can be efficacious

99 [41]

cold

(incl.

treatment

 

y/p

treatment, promising effects in

for the common cold, but evidence

  

combinations)

   

early treatment. Heterogen.

insufficient for recommendations

      

preparations

 

Melchart

immuno-

echinacea

placebo, no

18 RCT, 8

y/y/y/

Most studies low quality. Most

Echinacea extracts can be

94

stimulation

(incl.

treatment

CCT

y/n

studies show immunostimulating

efficacious immunostimulators, but

[42, 43]

 

combinations)

   

effects

evidence insufficient for

       

recommendations

Cranberries ( Vaccinium macrocarpon )

Jepson

urinary

cranberries

placebo

4 RCT

y/y/y/

In 3 of 4 trials cranberries effective

Insufficient evidence, further research

98 [44]

tract inf.

   

y/n

for at least one of the outcomes of

needed

 

(prevent)

    

interest

 

Jepson

urinary

cranberries

 

O RCT

y/y/-/

No trials meeting the inclusion

No evidence available

98 [45]

tract inf.

   

-/-

criteria

 
 

(treatm.)

      

Mistletoe ( Viscum album )

Kleijnen

cancer

mistletoe

placebo, no

11

y/y/y/

Most studies low quality. Most

Insufficient evidence to recommend

94 [46]

  

treatment

RCT/CCT

n/n

studies show longer survival with

mistletoe outside of clinical trials

      

mistletoe but not the best trial

 

Kiene 89

cancer

mistletoe

no treatment,

2 RCT, 33

y/n/n/

Most studies low quality. 9 of 12

Available evidence supports positive

[47, 48]

  

none

CCT, 11

y/n

interpretable studies suggest

effects of mistletoe

    

other

 

positive effects on survival

 
    

studies

   

Peppermint ( Mentha piperita )

Jailwala

irritable

1. peppermint

placebo

1. 3 RCT

p/y/y/

Chinese herbal therapy trial rated

In both cases efficacy not clearly

2000*

bowel

oil

 

2. 1 RCT

n/n

as positive, one of three

established

[49]

syndr.

2. Chinese

   

peppermint oil trials rated as

 
  

herbal

   

positive

 
  

therapy

     

Pittler 98

irritable

peppermint

placebo,

8 RCT

y/y/y/

Global improvement rates

The role of peppermint oil for IBS

[50]

bowel

oil

other

 

y/y

significantly higher compared to

has not been established beyond

 

syndr.

 

treatment

  

placebo. Quality of trials doubtful

reasonable doubt

Saw palmetto ( Serenoa repens )

Boyle

ben.

Permixon®

placebo,

11 RCTs,

?/n/n/

peak urine flow 2.20 (95% Cl 1.20–

Despite some limitations strong

2000 [51]

prostate

(saw

other

2 UCS

y/y

3.20) ml/s increase over placebo;

evidence that the extract tested has

 

hyperplasia

palmetto)

treatment

  

significant decrease nocturia

beneficial effects

Wilt 2000

ben.

saw palmetto

placebo,

14 RCT

y/y/y/

Saw palmetto superior to placebo

Evidence suggests that saw

&98

prostate

 

other

(plac),

y/y

for nocturia, self rating, peak urine

palmetto improves urological

[52, 53]

hyperplasia

 

treatment

5 RCT

 

flow; similar effects as finasteride

symptoms and flow measures.

    

(other)

  

Further studies needed

legend see table 1

Single systematic reviews have been published on aloe (Aloe vera) [54], artichoke (Cynara scolymus) leave extract [55], evening primrose (Oenothera biennis) oil [56], feverfew (Tanacetum parthenium) [57], ginger (Zingiber officinialis) [58], ginseng (Panax ginseng) [59], horse chestnut (Aesculus hippocastanum) seeds [60], kava (Piper methysticum) [61], milk thistle (Silybum marianum) [62], a fixed combination of three herbal extracts [63], rye-grass pollen (Secale cereale) extract [64, 65], tea tree (Melaleuca alternafolia) oil [66], and valerian (Valehana officinalis) root [67] (see table 4). The only review which focused on a herbal intervention which is not marketed as a drug or food supplement was on cabbage leaves for breast engorgement and included a single small-scale trial [68]. Chinese herbal therapy for atopic eczema [69] and a variety of herbs for lowering blood glucose [70] and for analgesic and anti-inflammatory purposes [71] have also been reviewed. For some of these herbal preparations the evidence is promising but further studies are considered necessary to establish efficacy in almost every case.
Table 4

Systematic reviews of clinical trials of herbal medicines

     

Features

  

Author

Indication

Intervention

Comparisons

Studies

1/2/3/

Results

Author's Conclusion

Year

    

4/5

  

Vogler 99

various

aloe

placebo, other

6 RCT,4

y/y/y/

Positive results for genital

Promising results, but overall

[54]

  

& no treatment

CCT

y/n

herpes, psoriasis, hyper-

evidence insufficient

      

lipidemia, diabetes;

 
      

contradictory for wound healing

 

Pittler 98

cholesterol

artichoke

placebo

1 RCT

y/y/y/

Effects over placebo only in the

More trials needed

[55]

lowering

leave

  

n/n

subgroup of participants with

 
  

extract

   

serum cholesterol > 210 mg/dl

 

Morse 89

atopic

evening

placebo

9

?/n/n/

Epogam significantly better

No conclusion drawn

[56]

eczema

primrose oil

 

RCT/CCT

y/y

than placebo for most

 
  

(Epogam)

   

outcomes

 

Vogler 98

migraine

feverfew

placebo

5 RCT

y/y/y/

Majority of trials favor feverfew

Effectiveness has not been

[57]

    

y/n

over placebo

established beyond reasonable

       

doubt

Ernst 2000

nausea and

ginger root

placebo,

6 RCT

y/y/y/

2 of 3 trials on postoperative

Evidence promising but insufficient

[58]

vomiting

 

metoclopramide

 

y/p

nausea positive (best

to draw firm conclusions

      

negative), trials on

 
      

seasickness, morning sickness

 
      

and chemotherapy-induced

 
      

nausea positive

 

Vogler 99

various

ginseng root

placebo, other

16 RCT

y/p/y/

Contradictory results re.

The efficacy of ginseng root extract

[59]

 

extract

treatment (1

 

y/n

physical performance (7 trials),

is not established beyond

   

trial)

  

psychological function (5),

reasonable doubt for any of these

      

immunomodulation (2),

indications

      

positive results in diabetes and

 
      

herpes simplex (1 trial

 
      

respectively)

 

Pittler 98

venous

horse

placebo, other

13 RCT

y/y/y/

Significant effects over placebo

horse chestnut seeds seem to be

[60]

insufficieny

chestnut

treatment

 

y/n

and similar effects compared to

effective; further tials needed

  

seeds

   

other treatments

(confirmation, long-term results,

       

combination)

Pittler 2000

anxiety

kava

placebo

7 RCT

y/y/y/

All trials suggest superiority

Available data suggest that kava is

[61]

    

p/p

over placebo; 3 trials with data

a treatment option for anxiety.

      

for meta-analysis show sign.

Further studies needed

      

superiority

 

Lawrence

liver

milk thistle

placebo, other

33 RCT,

y/y/y/

Variety of conditions studied,

Efficacy is not established.

2000 [62]

diseases

 

& no treatment

1 CCT

y/y

studies often poor quality.

Possible benefit shown most

      

Mixed and inconsistent findings

frequently for aminotransferases.

Ernst 99

musculoskel.

Phytodolor®

placebo, other

10 RCT

y/p/y/

Placebo-controlled trials show

The data suggest that the

[63]

pain

populus,

treatments

 

y/n

superiority over placebo and

combination is effective in the

  

fraxinus,

   

similar effects as NSAIDs

symptomatic treatment of

  

solidago

    

muskuloskeletal pain

MacDonald

ben. prostata

rye grass

placebo, other

4 RCT

y/y/y/

Signif. improvement over

Available evidence suggests that

2000 &

hyperplasia

pollen

therapy

 

y/y

placebo in subjective, but not

Cernilton® is well tolerated and

Wilt 2000

 

extract

   

objective symptoms; no

modestly improves subjective

[64, 65]

     

differences compared to

symptoms. Further studies needed

      

tadenan and paraprost

 

Ernst 2000

dermatologic

tea trea oil

placebo, other

4 RCT

y/y/y/

2 trials vs. placebo positive, 3

Data promising but insufficient

[66]

conditions

 

treatment

 

y/n

trials vs. other treatments

 
      

similar effects

 

Stevinson

insomnia

valerian root

placebo

9 RCT

y/y/y/

Highly heterogeneous studies

Available evidence is promising but

2000 [67]

    

y/n

with sometimes contradictory

not fully conclusive. Further,

      

and inconsistent findings

rigorous trials needed

Renfrew

breast

cabbage

usual care

1 RCT

y/y/n/

fewer women stopping breast

Further research desirable

84 [68]

engorgement

leaves

  

y/n

feeding among those receiving

 
      

cabbage leaves

 

Armstrong

atopic

Chinese

placebo

2 RCT

y/y/n/

2 positive studies by the same

Evidence encouraging but

99 [69]

eczema

herbal

  

y/n

 

insufficient given the potential of

  

therapy

   

treat analysis

relevant side effects

Ernst 97

hypoglyc.

all plants

no treatment,

7 RCT, 4

y/p/n/

Most studies low quality. Most

Use of hypoglcemic plant remedies

[70]

activity

 

placebo, none

CCT, 10

y/n

papers report positive effects

not supported by rigorous

    

UCS

 

on a variety of plants

research. Further studies required

Ernst 2000

analgetic or

various

placebo

18 RCT

y/y/y/

Trials on evening primrose oil,

The results suggest that several

[71]

inflamm.

   

y/n

blackcurrant seed oil, borage

herbal remedies have potential in

 

treatment

    

oil, harpagophytum, willow

alleviating the pain of rheumatic

      

bark, feverfew, and 3

diseases. More research urgently

      

combinations; almost all trials

needed

      

positive

 

legend see table 1

Discussion

Our overview shows that a considerable number of systematic reviews on herbal medicines is available. In the majority of cases the reviewers considered the available evidence as promising but only very rarely as convincing and sufficient as a firm basis for clinical decisions. The methodological quality of the primary studies has been criticized by many reviewers.

Our summary of the existing studies must be interpreted with caution. What we performed is a systematic review of systematic reviews which inherently bears a large risk of oversimplification. Readers who want to reliably assess the evidence for a given herb for a defined condition should read the respective reviews. Our collection – which to the best of our knowledge is complete up to summer 2000 – is aimed at facilitating the access and giving an idea of the amount of the available evidence. Based on the increase of herbal medicine reviews in recent years we expect that at least ten new publications will become available in the year 2001.

Most of the currently available systematic reviews address herbal preparations which are marketed and widely used in industrialized countries. However, the widespread traditional use of herbs in the Third World is rarely ever investigated and has not been subjected to systematic reviews. The many herbs used in folk medicine or other traditional uses of herbs (for example, hypericum is used for a variety of ailments other than depression including enuresis, diarrhoea, gastritis, bronchitis, asthma, sleeping disorders etc.) seem to be rarely investigated. Furthermore, practitioners of herbal medicine often combine different herbs and use unconventional diagnostic approaches to adapt prescriptions to single patients. It seems likely that these traditional forms of herbal medicine will remain underresearched relative to single herbal preparations due to the lack of financial incentive for sponsors and due to methodological problems.

Herbal medicines products are not, in general, subject to patent protection. This reduces the motivation for drug companies to invest in trials. Many of the existing herbal medicine manufacturers are comparably small companies, often with limited research resources and expertise. Maybe partly for these reasons, the quality of many older herbal medicine trials is low. Furthermore, negative trials which could threaten the company's survival might not become published.

A fundamental problem in all clinical research of herbal medicines is whether different products, extracts, or even different lots of the same extract are comparable and equivalent. This is a major issue in the expert research community and a major obstacle to a reliable assessment for the non-expert. For example, Echinacea products can contain other plant extracts, use different plant species (E. purpurea, pallida or angustifolia), different parts (herb, root, both), and might have been produced in quite different manners (hydro- or lipophilic extraction). Pooling studies that use different herbal products in a quantitative meta- analysis can be misleading. Health care professionals and patients considering to prescribe or take a particluar herbal product should check carefully whether the respective product or extract has been tested in the trials included in a review. On the health food store shelf the high quality, standardized products used in the trials might not be available. Only a herbal medicine expert can judge with some certainty whether the results can be extrapolated to the product of interest.

On the level of health care policies the available systematic reviews more often provide insight into the deficiencies of the evidence than guidance for decision making. Trials on hard endpoints are very rarely available and observation periods have generally been short. The clinical relevance of the observed effects is not always clear.

Herbal medicines are generally considered as comparably safe. While this is probably correct case reports show that severe side effects and relevant interactions with other drugs can occur. For example, hypericum extracts cause considerably fewer side effects than tricyclic antidepressants [92] but can decrease the concentration of a variety of other drugs by enzyme induction [93]. Several reviews summarizing side effects and interactions have been published [9498].

In conclusion, the systematic reviews collected for this analysis are a good tool to get an overview of the available evidence from clinical trials in the area of herbal medicine. However, applying the findings to patients care is problematic for those who are not experts in herbal medicine. In this case it might be better to directly search the literature for clinical trials of the respective product.

Declarations

Acknowledgements

KL's work was partly funded by the NIAMS grant 5 U24-AR-43346-02 and by the Carl and Veronica Carstens Foundation, Essen, Germany. We would like to thank Brian Berman for his support, his help to get funding and his patience in awaiting the completion of our work.

Authors’ Affiliations

(1)
Centre for Complementary Medicine Research, Department of Internal Medicine II, Technische Universität
(2)
Institute for Social Medicine & Epidemiology, Charité Hospital, Humboldt University
(3)
HS Centre for Reviews & Dissemination, University of York
(4)
Department of Epidemiology, Maastricht University
(5)
Consortial Center for Chiropractic Research
(6)
Memorial Sloan-Kettering Cancer Center
(7)
Division of Complementary Medicine Department of Internal Medicine, Universitätsspital Zurich

References

  1. Vickers A, Zollman CE: ABC of complementary medicine: herbal medicine. BMJ. 1999, 319: 1050-1053.PubMed CentralView ArticlePubMed
  2. Schwabe U: Arzneimittel der besonderen Therapierichtungen (Naturheilmittel). In Arzneiverordnungs-Report 1998. Edited by Schwabe U, Paffrath D. Berlin: Springer,. 1999, 621-656.View Article
  3. Brevoort P: The booming US botanical market. A new overview. HerbalGram. 1998, 44: 33-51.
  4. Barnes J: Phytotherapy: consumer and pharmacist perspectives. In: Herbal medicine – a concise overview for professionals. Edited by Ernst E. Oxford: Butterworth Heinemann,. 2000, 19-33.
  5. Bodeker GC: Editorial. J Altem Complement Med. 1996, 3: 323-326.View Article
  6. Linde K, Vickers A, Hondras M: Systematic reviews of complementary therapies – an annotated bibliography. Part 1: acupuncture. BMC Complementary and Alternative Medicine. 2001, 1: 3-10.1186/1472-6882-1-3.PubMed CentralView ArticlePubMed
  7. Pittler MH, Ernst E: Ginkgo biloba extract for the treatment of intermittent claudication: a meta- analysis of randomized trials. Am J Med. 2000, 108: 276-281. 10.1016/S0002-9343(99)00454-4.View ArticlePubMed
  8. Moher D, Pham B, Ausejo M, Saenz A, Hood S, Barber GG: Pharmacological management of intermittent claudication: a meta-analysis of randomised trials. Drugs. 2000, 59: 1057-1070.View ArticlePubMed
  9. Ernst E: Ginkgo biloba in der Behandlung der Claudicatio intermittens. Fortschr Med. 1996, 114: 85-87.PubMed
  10. Schneider B: Ginkgo-biloba-Extrakt bei peripheren arteriellen Verschlusskrankheiten. Meta Analyse von kontrollierten klinischen Studien. Arzneim-Forsch/Drug Res. 1992, 42(1): 428-436.
  11. Letzel H, Schoop W: Gingko-biloba-Extrakt EGb 761 und Pentoxifyllin bei Claudicatio intermittens. Sekundäranalyse zur klinischen Wirksamkeit. VASA. 1992, 21: 403-410.PubMed
  12. Kleijnen J, Knipschild P: Gingko biloba for intermittent claudication and cerebral insufficiency. In: Kleijnen J. Food supplements and their efficacy. Maastricht: Rijksuniversiteit Limburg,. 1991, 83-94.
  13. Weiss G, Kallischnigg G: Gingko-biloba-Extrakt (EGb 761) – Meta-Analyse von Studien zum Nachweis der therapeutischen Wirksamkeit bei Hirnleistungsstorungen bzw. peripherer arterieller Verschlusskrankheit. Muench med Wschr. 1991, 10: 138-142.
  14. Ernst E, Pittler MH: Ginkgo biloba for dementia: a systematic review of double-blind, placebo- controlled trials. Clin Drug Invest. 1999, 17: 301-308.View Article
  15. Oken BS, Storzbach DM, Kaye JA: The efficacy of ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol. 1998, 55: 1409-1415. 10.1001/archneur.55.11.1409.View ArticlePubMed
  16. Hopfenmuller W: Nachweis der therapeutischen Wirksamkeit eines Ginkgo biloba-Spezialextraktes – Meta-Analyse von 11 klinischen Studien mit Patienten mit Hirnleistungsstörungen im Alter. Arzneim-Forsch /Drug Res. 1994, 44(ll): 1005-1013.
  17. Kleijnen J, Knipschild P: Gingko biloba for cerebral insufficiency. Br J din Pharmacol. 1992, 34: 352-358.View Article
  18. Ernst E, Stevinson C: Ginkgo biloba for tinnitus: a review. Clin Otolaryngol. 1999, 24: 164-167. 10.1046/j.1365-2273.1999.00243.x.View ArticlePubMed
  19. Evans JR: Ginkgo biloba extract for age-related macular degeneration (Cochrane Review). In: The Cochrane Library, Issue 1. 2000, . Oxford: Update Software.
  20. Gaster B: St John's wort for depression. A systematic review. Arch Intern Med. 2000, 160: 152-156. 10.1001/archinte.160.2.152.View ArticlePubMed
  21. Williams JW, Mulrow CD, Chiquette E, Hitchcock Noel P, Aguilar C, Cornell J: A systematic review of newer pharmacotherapies for depression in adults: Evidence report summary. Ann Int Med. 2000, 132: 743-756.View ArticlePubMed
  22. Mulrow CD, Williams JW, Trivedi M: Treatment of depression – newer pharmacotherapies. Psychopharmacol Bull. 1998, 34: 409-795.PubMed
  23. Kim HL, Streltzer J, Goebert D: St. John's wort for depression: A meta-analysis of well-defined clinical trials. J Nerv Ment Dis. 1999, 187: 532-539. 10.1097/00005053-199909000-00002.View ArticlePubMed
  24. Stevinson C, Ernst E: Hypericum for depression. An update of the clinical evidence. Neuropsychopharmacol. 1999, 9: 501-505. 10.1016/S0924-977X(99)00032-2.View Article
  25. Linde K, Mulrow CD: St John's wort for depression (Cochrane Review). In: The Cochrane Library, Issue 4. 1998, . Oxford: Update Software.
  26. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D: St John's wort for depression – an overview and meta-analysis of randomised clinical trials. BMJ. 1996, 313: 253-258.PubMed CentralView ArticlePubMed
  27. Volz HP: Controlled clinical trials of hypericum extract in depressed patients – an overview. Pharmacopsychiat. 1997, 30 (suppl): 72-75.View Article
  28. Ernst E: St. John's Wort, an anti-depressant? A systematic, criteria-based review. Phytomedicine. 1995, 2: 67-71.View ArticlePubMed
  29. Volz HP, Laux P: Potential treatment for subthreshold and mild depression: A comparison of St. John's wort extracts and fluoxetine. Comprehensive Psychiatry. 2000, 41 (suppl 1): 133-137.View Article
  30. Friede M, Wüstenberg P: Johanniskraut zur Therapie von Angstsyndromen bei depressiven Verstimmungen. Ztschr Phytother. 1998, 19: 309-317.
  31. Lawrence V, Mulrow C, Ackerman R: Garlic: Effects on cardiovascular risks and disease, protective effects against cancer, and clinical adverse effects. Evidence Report/Technology Assessment: Number 20. 2000, [http://www.ahcpr.gov/clinic/garlicsum.htm]
  32. Stevinson C, Pittler MH, Ernst E: Garlic for treating hypercholesterinemia – a meta-analysis of randomized clinical trials. Ann Intern Med. 2000, 133: 420-429.View ArticlePubMed
  33. Silagy C, Neil A: Garlic as a lipid lowering agent – a meta-analysis. J Roy Coll Phys. 1994, 28: 39-45.
  34. Neil HAW, Silagy CA, Lancaster : Garlic powder in the treatment of moderate hyperlipidaemia: a controlled trial and meta-analysis. J Roy Coll Pract London. 1996, 30: 329-334.
  35. Warshafsky S, Kamer RS, Sivak SL: Effect of garlic on total serum cholesterol. Ann Int Med. 1993, 119: 599-605.View ArticlePubMed
  36. Silagy CA, Neil HA: A meta-analysis of the effect of garlic on blood pressure. J Hypertension. 1994, 12: 463-468.View Article
  37. Kleijnen J: Controlled clinical trials in humans on the effects of garlic supplements. In: Kleijnen J. Food supplements and their efficacy. Maastricht: Rijksuniversiteit Limburg,. 1991, 73-82.
  38. Kleijnen J, Knipschild P, ter Riet G: Garlic, onions and cardiovascular risk factors. A review of the evidence from human experiments with emphasis on commercially available preparations. Br J Clin Pharmacol. 1989, 28: 535-544.PubMed CentralView ArticlePubMed
  39. Jepson RG, Kleijnen J, Leng GC: Garlic for lower limb atherosclerosis (Cochrane Review). In: The Cochrane Library, Issue 4. 1998, . Oxford: Update Software.
  40. Barrett B, Vohmann M, Calabrese C: Echinacea for upper respiratory tract infection. J Fam Pract. 1999, 48: 628-635.PubMed
  41. Melchart D, Linde K, Fischer P, Kaesmayr J: Echinacea for prevention and treatment of the common cold (Cochrane Review). In: The Cochrane Library, Issue 1. 1999, . Oxford: Update Software.
  42. Melchart D, Linde K, Worku F, Bauer R, Wagner H: Immunmodulation mit Echinacea-haltigen Arzneimittein – eine kriteriengestützte Analyse der kontrollierten klinischen Studien. Forsch Komplementärmed. 1994, 1: 26-36.View Article
  43. Melchart D, Linde K, Worku F, Bauer R, Wagner H: Immunomodulation with Echinacea – a systematic review of controlled clinical trials. Phytomedicine. 1994, 1: 245-254.View ArticlePubMed
  44. Jepson RG, Mihaljevic L, Craig J: Cranberries for the prevention of urinary tract infections (Cochrane Review). In The Cochrane Library, Issue 4. 1998, . Oxford: Update Software.
  45. Jepson RG, Mihaljevic L, Craig J: Cranberries for the treatment of urinary tract infections (Cochrane Review). In The Cochrane Library, Issue 4. 1998, . Oxford: Update Software.
  46. Kleijnen J, Knipschild P: Mistletoe treatment for cancer. Review of controlled trials in humans. Phytomedicine. 1994, 1: 255-260.View ArticlePubMed
  47. Kiene H: Klinische Studien zur Misteltherapie karzinomatöser Erkrankungen. Therapeutikon. 1989, 6: 347-353.
  48. Kiene H: Klinische Studien zur Misteltherapie der Krebserkrankung. Eine kritische Würdigung. Herdecke: Dissertation,. 1989
  49. Jailwala J, Imperiale TF, Kroenke K: Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000, 133: 136-147.View ArticlePubMed
  50. Pittler MH, Ernst E: Peppermint oil for irritable bowel syndrome: a critical review and meta- analysis. Am J Gastroenterol. 1998, 93: 1131-1135. 10.1016/S0002-9270(98)00224-X.View ArticlePubMed
  51. Boyle P, Robertson C, Lowe F, Roehborn C: Meta-analysis of clinical trials of Permixon in the treatment of symptomatic benign prostatic hyperplasia. Urology. 2000, 55: 533-539. 10.1016/S0090-4295(99)00593-2.View ArticlePubMed
  52. Wilt TJ, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J: Serenoa repens for treatment of benign prostatic hyperplasia (Cochrane Review). In: The Cochrane Library, Issue 1. 2000, . Oxford: Update Software.
  53. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C: Saw palmetto extracts for treatment of benign prostatic hyperplasia – a systematic review. JAMA. 1998, 280: 1604-1609. 10.1001/jama.280.18.1604.View ArticlePubMed
  54. Vogler BK, Ernst E: Aloe vera: A systematic review of its clinical effectiveness. Br J Gen Pract. 1999, 49: 823-828.PubMed CentralPubMed
  55. Pittler MH, Ernst E: Artichoke leaf extract for serum cholesterol reduction. Perfusion. 1998, 11: 338-340.
  56. Morse PF, Horrobin DF, Manku MS: Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and responses. Br J Dermatol. 1989, 121: 75-90.View ArticlePubMed
  57. Vogler BK, Pittler MH, Ernst E: Feverfew as a preventive treatment for migraine: a systematic review. Cephalalgia. 1998, 18: 704-708. 10.1046/j.1468-2982.1998.1810704.x.View ArticlePubMed
  58. Ernst E, Pittler MH: Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Intern J Anesth. 2000, 84: 367-371.
  59. Vogler BK, Pittler MH, Ernst E: The efficacy of ginseng. A systematic review of randomised clinical trials. Eur J Clin Pharmacol. 1999, 55: 567-575. 10.1007/s002280050674.View ArticlePubMed
  60. Pittler MH, Ernst E: Horse-chestnut seed extract for chronic venous insufficiency. Arch Dermatol. 1998, 134: 1356-1360. 10.1001/archderm.134.11.1356.View ArticlePubMed
  61. Pittler MH, Ernst E: Efficacy of kava extract for treating anxiety: systematic review and meta- analysis. J Clin Psychopharmacol. 2000, 20: 84-89. 10.1097/00004714-200002000-00014.View ArticlePubMed
  62. Lawrence V, Mulrow C, Jacobs B: Report on milk thistle: Effects on liver disease and cirrhosis and clinical adverse effects. Evidence Report/Technology Assessment: Number 21. [http://www.ahcpr.gov/clinic/milktsum.htm]
  63. Ernst E: The efficacy of Phytodolor for the treatment of musculoskeletal pain – a systematic review of randomized clinical trials. Natural Medicine Journal. 1999, Summer: 14-7.
  64. MacDonald R, Ishani A, Rutks I, Wilt TJ: A systematic review of Cernilton for the treatment of benign prostatic hyperplasia. Br J Urol Int. 2000, 85: 836-841. 10.1046/j.1464-410x.2000.00365.x.View Article
  65. Wilt TJ, MacDonald R, Ishani A, Rutks I, Stark G: Cernilton for benign prostatic hyperplasia (Cochrane Review). In: The Cochrane Library, Issue 2. 2000, . Oxford: Update Software.
  66. Ernst E, Huntley A: Tea tree oil: a systematic review of randomised clinical trials. Forsch Komplementärmed. 2000, 7: 17-20. 10.1159/000057164.View Article
  67. Stevinson C, Ernst E: Valerian for insomnia: a systematic review of randomized clinical trials. Medicine. 2000, 1: 91-99. 10.1016/S1389-9457(99)00015-5.
  68. Renfrew MJ, Lang S: Do cabbage leaves prevent breast engorgement? (Cochrane Review). In: The Cochrane Library, Issue 4. 1998, . Oxford: Update Software.
  69. Armstrong NC, Ernst E: The treatment of eczema with Chinese herbs: a systematic review of randomized controlled trials. Br J Clin Pharmacol. 1999, 48: 262-264. 10.1046/j.1365-2125.1999.00004.x.PubMed CentralView ArticlePubMed
  70. Ernst E: Plants with hypoglycaemic activity in humans. Phytomedicine. 1997, 4: 73-78.View ArticlePubMed
  71. Ernst E, Chrubasik S: Phyto-anti-inflammatories: a systematic review of randomized, placebo- controlled, double-blind trials. Rheum Dis Clin North America. 2000, 26: 13-27.View Article
  72. Budeiri D, Li Wan Po A, Dornan JC: Is Evening Primrose Oil of value in the treatment of premenstrual syndrome?. Controlled Clin Trials. 1996, 17: 60-68. 10.1016/0197-2456(95)00082-8.View ArticlePubMed
  73. Diehm C: The role of oedema protective drugs in the treatment of venous insufficiency: a review of evidence based on placebo-controlled clinical trials with regard to efficacy and tolerance. Phlebology. 1996, 11: 23-29.
  74. Evans MF, Morgenstern K: St. John's wort: an herbal remedy for depression?. Canadian Family Physician. 1997, 43: 1735-1736.PubMed CentralPubMed
  75. Giles JT, Palat CR, Chien SH, Chang ZG, Kennedy DT: Evaluation of echinacea for treatment of the common cold. Pharmacotherapy. 2000, 20: 690-697.View ArticlePubMed
  76. Josey ES, Tackett RL: St. John's wort: a new alternative for depression?. Intern J Clin Pharmacol Ther. 1999, 37: 111-119.
  77. Kleijnen J, ter Riet G, Knipschild P: Teunisbloemolie. Een overzichtvan gecontroleerd onderzoek. Pharmaceutisch Weekblad. 1989, 124: 418-423.
  78. Knipschild P: Ginseng: pep of nep?. Pharmaceutisch Weekblad. 1988, 123: 4-11.
  79. McPartland JM, Pruitt PL: Medical marijuana and its use by the immunocompromised. Altern Ther Health Med. 1997, 3: 39-45.PubMed
  80. Weihmayr T, Ernst E: Die therapeutische Wirksamkeit von Crataegus. Fortschr Med. 1996, 114: 27-29.PubMed
  81. Wettstein A: Cholinesterase inhibitors and ginkgo extracts – are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months duration. Phytomed. 2000, 6: 393-401.View Article
  82. Wong AHC, Smith M, Boon HS: Herbal remedies in psychiatric practice. Arch Gen Psychiatry. 1998, 55: 1033-1044. 10.1001/archpsyc.55.11.1033.View ArticlePubMed
  83. Ernst E, Pittler MH: Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. 1998, 159: 433-436.View ArticlePubMed
  84. Mclntosh HM, Olliaro P: Artemisin derivatives for treating uncomplicated malaria (Cochrane Review). In: The Cochrane Library, Issue 2. 2000, . Oxford: Update Software.
  85. Mclntosh HM, Olliaro P: Artemisin derivatives for treating severe malaria (Cochrane Review). In: The Cochrane Library, Issue 2. 2000, . Oxford: Update Software.
  86. Pittler MH, Ernst E: Artemether for severe malaria: a meta-analysis of randomized clinical trials. Clin Infect Dis. 1999, 28: 597-601.View ArticlePubMed
  87. Wilt TJ, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J: Beta-sitosterols for benign prostatic hyperplasia (Cochrane Review). In: The Cochrane Library, Issue 1. 2000, . Oxford: Update Software.
  88. Dumont L, Mardirosoff C, Tramér M: Efficacy and harm of pharmacological prevention of acute mountain sickness: a quantiative systematic review. BMJ. 2000, 321: 267-272. 10.1136/bmj.321.7256.267.PubMed CentralView ArticlePubMed
  89. Ernst E: Can allium vegetables prevent cancer?. Phytomed. 1997, 4: 79-83.View Article
  90. Joy CB, Mumby-Croft R, Joy LA: Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia (Cochrane Review). In: The Cochrane Library, Issue 2. 2000, . Oxford: Update Software.
  91. Young GL, Jewell MD: Creams to prevent striae gravidarum (Cochrane Review). In: The Cochrane Library, Issue 4. 1998, . Oxford: Update Software.
  92. Ernst E, Rand Jl, Barnes J, Stevinson C: Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol. 1998, 54: 589-594. 10.1007/s002280050519.View ArticlePubMed
  93. Ernst E: Second thoughts about safety of St John's wort. Lancet. 1999, 354: 2014-2015. 10.1016/S0140-6736(99)00418-3.View ArticlePubMed
  94. De Smet PAGM: Health risks of herbal remedies. Drug Safety. 1995, 13: 81-93.View ArticlePubMed
  95. Miller LG: Herbal medicine. Selected clinical considerations focusing on known or potential drug- herb interactions. Arch Intern Med. 1998, 158: 2200-2211. 10.1001/archinte.158.20.2200.View ArticlePubMed
  96. Fugh-Berman A: Herb-drug interactions. Lancet. 2000, 355: 134-138. 10.1016/S0140-6736(99)06457-0.View ArticlePubMed
  97. Ernst E: Possible interactions between synthetic and herbal medicinal products. Part 1: a systematic review of the indirect evidence. Perfusion. 2000, 13: 4-15.
  98. Ernst E: Possible interactions between synthetic and herbal medicinal products. Part 2: a systematic review of the direct evidence. Perfusion. 2000, 13: 60-70.
  99. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/content/backmatter/1472-6882-1-5-b1.pdf

Copyright

© Linde et al; licensee BioMed Central Ltd. 2001

This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

Advertisement