Meta-Analysis to Assess the Efficacy of Phytotherapy
A Short Bibliography

Background: Use of herbal treatment is increasing, especially in the west. This brief note summarises the results of a Medline search on controlled trials of phytotherapy in humans that had been subjected by others to meta-analysis.

Medline Abstracts: A Medline search on December 10th, 2001, yielded >34473 hits for the profile: [herbal-medicine OR herbal-therapy OR medical-herbal* OR medicinal-herb* OR phytotherapy OR plant-therapy].

Limitation of the Medline search to Abstracts of Meta-Analysis studies yielded 40 relevant hits. In the table below, the hits are classified as follows: cancer, cardiovascular disease, central nervous system, gastrointestinal system, general, reproductive system, respiratory disease and skin disease. The slightly shortened abstracts are appended below.

Conclusions:

1. There are hundreds of thousands of scientific reports on phytotherapy of disease (especially human disease), and on research on the active ingredients in herbal remedies and their modes of action. Unfortunately most reports are in specialist oriental language journals that largely preclude western access to them, or scientific appreciation of their value. Meta-analysis is only one way to examine published data for therapeutic efficacy; masses of other data suggest positive effects from many phytotherapeutic agents or combinations, such as those used in Chinese herbal formulas.
2. In the meta-analytical studies, the role of tea consumption as an adverse factor in CHD and stroke is controversial. Although promising, the role of Chinese herbs in ezcema, Evening Primrose Oil in PMT, Olive Oil in cancer, Urtica dioica and Curcubita pepo in prostate hypertrophy, and of valerian as a mild sedative remains inconclusive.
3. Overall, there is evidence from meta-analysis of controlled trials that phytotherapy with Aesculus (6); Fibrous foods (1, 35); Fruit & vegetables (8, 18, 32, 33); Garlic (7, 30, 31, 34, 36); Ginkgo biloba (6, 13, 25, 29, 37); Hypericum perforatum (6, 11, 12, 16, 19); Hypoxis rooperi (38); Kava (26); Nuts (14); Peppermint oil (24); Psyllium-enriched cereal (22); Pygeum africanum (15, 38); Rice in rehydration fluid (10); Secale cereale (38); Serenoa repens (3, 6, 38, 39); Soya/Herbal Tea (9, 40) and Yohimbe (6) gave significant benefit in many human diseases.
4. Because of these results, the role of these and other phytotherapeutic agents in animal disease merits serious research.
   

Table 1. Summary of Medline hits on meta-analytical studies of phytotherapy, classified by clinical condition or body system.
Cancer

Bladder
Colo-rectal/Stomach
Many locations
Mammary & other

Fruit & vegetables (32)
Fibrous foods (35), Garlic (7), Soya (40)
Fruit & vegetables 33
Fruit & vegetables (8), Olive oil 20

Cardiovascular disease

Cardiovascular Disease
CHD/ Ischaemic heart disease
Hypertension
Intermittent claudication/Peripheral arterial disease
Hypercholesterolaemia
Venous insufficiancy - chronic

Tea (23)
Fibrous foods (1), Fruit & vegetables (18), Nuts (14)
Garlic (30, 34, 36), Psyllium-enriched Kellogg's (!!) cereal (22)
Garlic (31)
Ginkgo biloba or its extract (25, 29)
Aesculus (6)

Central nervous system

Dementia
Anxiety
Geriatric Cerebrovascular insufficiency

Depression

Ginkgo (6, 37)
Kava extract (26)
Ginkgo biloba special extract LI 1370, Kaveri Forte (13)
Hypericum perforatum (6, 11 , 12, 16, 19)

Gastrointestinal system

Colic - Infantile
Rehydration in severe diarrhoea
IBS (Irritable Bowel Syndrome)

Soya, Herbal Tea (9)
Rice in rehydration fluid (10)
Peppermint oil (24)

General

Geriatric medicine

Unsafe and potentially safe herbal therapies

Gingko, Hypericum, Serenoa, Yohimbe, Aesculus and Valerian (6)
(17)

Reproductive system

Benign prostatic hypertrophy (BPH)

Erectile dysfunction
Premenstrual syndrome

Serenoa (3, 6, 38, 39); Pygeum (15, 38); Hypoxis, Secale, Urtica, Curcubita (38)
Yohimbine (6)
Evening primrose oil (4)

Respiratory disease

Allergic rhinitis, Pollenosis

Asthma
Bronchial response to allergens

specific immunotherapy (28), Homeopathic Galphimia glauca (21)
specific immunotherapy (27)
Bronchial responsiveness to allergens (5)

Skin Disease

Eczema

Chinese herbs (2)

Slightly shortened abstracts from Medline

1. Anderson JW, Hanna TJ, Peng X, Kryscio RJ. J Am Coll Nutr 2000 Jun;19(3 Suppl):291S-299S. Whole grain foods and heart disease risk. Div of Biostatistics, VA Medical Ctr and Univ of Kentucky, Lexington, USA. CHD is the main cause of death in most developed nations and is rapidly increasing in prevalence in developing countries. Death rates from cardiovascular disease exceed 1 million annually in the USA and account for the largest disease-related cost to health with total costs estimated to exceed $120 billion per annum. Many dietary factors, including total and saturated fat consumption, fruit and vegetable intake and dietary fibre, have been shown to contribute to risk for CHD. We have systematically reviewed literature from the past 20 years evaluating an association between dietary fibre and CHD. Foods that are rich in dietary fibre, including fruits, vegetables, legumes and whole grain cereals, also tend to be a rich source of vitamins, minerals and phytochemicals. antioxidants and other micronutrients. Each of these factors may be independently contributing to the cardiovascular protective effects of fibre-rich foods. Publication Types: Meta-Analysis
2. Armstrong NC, Ernst E. Br J Clin Pharmacol 1999 Aug;48(2):262-4. Treatment of eczema with Chinese herbs: a systematic review of randomised clinical trials. Dept of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, Univ of Exeter, 25 Victoria Park Road, Exeter EX2 4NT. AIMS: Chinese herbal treatments are being promoted as a treatment for eczema. The aim of this study was to systematically review the evidence for or against this notion. METHODS: Extensive literature searches were carried out to identify all randomised clinical trials on the subject. Data were extracted from these in a predefined standardised fashion. RESULTS: Only two randomised clinical trials were located. Both imply that a complex mixture of Chinese herbs is more effective than placebo in treating eczema. Yet several caveats exist, most importantly the lack of independent replication. Adverse effects have also been reported. CONCLUSION: It is unclear whether Chinese herbal treatments of eczema do more good than harm. Publication Types: Meta-Analysis
3. Boyle P, Robertson C, Lowe F, Roehrborn C. Urology 2000 Apr;55(4):533-9. Meta-analysis of clinical trials of permixon in the treatment of symptomatic benign prostatic hyperplasia. Div of Epidemiology, European Inst of Oncology, Milan, Italy. OBJECTIVES: Permixon is a compound extracted from the fruit of the American dwarf palm tree, Serenoa repens. Controversy regarding the use of phytotherapeutic agents in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia is significant. We analysed all available clinical trial data of the Permixon preparation to determine its clinical efficacy compared with placebo. METHODS: All published clinical trial data on Permixon (11 randomised clinical trials and 2 open label trials), involving 2859 patients, were used. These trials were disparate in size (from 22 to 592 patients) and duration (from 21 to 180 days). Peak urinary flow rate and nocturia were the two common end points. The statistical analysis was based on a random effects meta-analysis. RESULTS: The average+/-SE placebo effect on the peak urinary flow rate was an increase of 0.51+/-0.51 mL/s. The estimated effect of Permixon was a further increase of 2.20+/-0.51 mL/s (P <0.001). Placebo was associated with a reduction in the mean number+/-SE of nocturnal urinations of 0.69+/-0.15. A further reduction of 0.50+/-0.01 episodes of urination (P <0.001) occurred that was attributable to Permixon. Some heterogeneity was found among the studies. Treatment duration did not appear to impact either of these effects. CONCLUSION: This meta-analysis of all available published trials of Permixon in the treatment of men with benign prostatic hyperplasia revealed a significant improvement in peak flow rate and reduction in nocturia greater than with placebo. Publication Types: Meta-Analysis
4. Budeiri D, Li Wan Po A, Dornan JC. Control Clin Trials 1996 Feb;17(1):60-8. Is evening primrose oil of value in the treatment of premenstrual syndrome? School of Pharmacy, Queen's Univ of Belfast, UK. A systematic literature search of clinical trials of evening primrose oil (EPO) for the treatment of the premenstrual syndrome (PMS) was carried out with a view to performing a meta-analysis. Only seven placebo-controlled trials were found but only in five trials was randomisation clearly indicated. Inconsistent scoring and response criteria made statistical pooling and hence a rigorous meta-analysis inappropriate. The two most well controlled studies failed to show any beneficial effects for EPO, although because the trials were relatively small modest effects cannot be excluded. Nonetheless, on current evidence EPO is of little value in the management of premenstrual syndrome. Publication Types: Meta-Analysis
5. Chinn S, Burney P, Sunyer J, Jarvis D, Luczynska C. Eur Respir J 1999 Oct;14(4):876-84. Sensitisation to individual allergens and bronchial responsiveness in the ECRHS. European Community Respiratory Health Survey. Dept of Public Health Sciences, King's College, London, UK. Little is known about the relation of bronchial responsiveness (BHR) to sensitisation to individual allergens, or its variation between countries. Data were obtained for BHR, specific immunoglobulin E and confounding variables from 11,215 subjects, aged 20-44 yrs at the start of the European Community Respiratory Health Survey, in 34 centres in 15 countries. The relation of BHR to sensitisation to cat, house dust mite, timothy grass and Cladosporium was estimated by means of multiple regression for each centre. The study was combined across centres by random effects meta-analysis, controlling for baseline lung function, height, sex, season of testing, age, smoking and age/sex and age/smoking interactions. BHR was greater, on average, in those sensitised to cat (p=0.023), house dust mite (p<0.001) and timothy grass (p=0.018), but not to Cladosporium (p=0.60), and increased with degree of sensitisation (p<0.001). All relations showed heterogeneity between centres, although to a lesser extent in the relation to sensitisation to house dust mite. More variation in bronchial responsiveness was explained by sensitisation and degree of sensitisation to the individual allergens than by atopy defined as any positive test in each centre. However but the relative importance of each allergen varied. The use of atopy as a single variable in relation to bronchial hyperresponsiveness may be misleading. Publication Types: Clinical Trial Meta-Analysis Multicenter Study Randomised Controlled Trial
6. Ernst E. Drugs Aging 1999 Dec;15(6):423-8. Herbal medications for common ailments in the elderly. Dept of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, Univ of Exeter, England. [email protected] The popularity of herbal medicine is at an all time peak. This article provides an overview of systematic reviews of herbal treatments for conditions common in elderly individuals. According to this evidence, there is little doubt that Hypericum perforatum (St John's Wort) is well tolerated and effective for mild to moderate depression. Although widely used, 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 alleviate the subjective symptoms and reduce the objective signs of chronic venous insufficiency. Serenoa repens (saw palmetto) is effective in improving the symptoms of benign prostatic hyperplasia. Finally, yohimbine has been shown to be effective for erectile dysfunction. Conclusion: Several plant-based medicines can be useful additions to our therapeutic repertoire for treating common conditions in the elderly. However, several uncertainties remain and, at present, prevent unreserved recommendations. Publication Types: Meta-Analysis
7. Fleischauer AT, Poole C, Arab L. Am J Clin Nutr 2000 Oct;72(4):1047-52. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Depts of Epidemiology and Nutrition, Univ of North Carolina, Chapel Hill, NC 27599, USA. BACKGROUND: Animal and in vitro studies have provided evidence of an anticarcinogenic effect of active ingredients in garlic. OBJECTIVE: The objective was to conduct meta-analyses of the epidemiologic literature on the association between garlic consumption and risk of stomach, colon, head and neck, lung, breast, and prostate cancers. DESIGN: Meta-analyses were conducted for all cancers mutually and separately for colorectal and stomach cancers in relation to consumption of exclusively raw garlic, cooked garlic, or both (RC garlic). Eighteen studies reported a relative risk estimate for RC garlic consumption and cancer risk. RESULTS: In the meta-analyses of colorectal and stomach cancer, the reference categories ranged from no consumption to consumption of 3.5 g/wk, whereas the highest categories ranged from any consumption to >28.8 g/wk. The average difference between the highest and lowest categories was 16 g/wk. The random-effects relative risk (RR) estimate of colorectal cancer and RC garlic consumption, excluding garlic supplements, was 0.69 (95% CI: 0.55, 0.89). For stomach cancer, the random-effects RR estimate was 0.53 (95% CI: 0.31, 0.92). The heterogeneity among studies for the latter outcome (P=0.0002) indicates the questionableness of the generalizability of this summary estimate. An indication of publication bias for all cancers combined is evident from a funnel plot of RC garlic consumption and cancer risk and from the results of the Begg and Mazumdar test (P:=0.049). CONCLUSION: High intake of RC garlic may be associated with a protective effect against stomach and colorectal cancers. Heterogeneity of effect estimates, differences in dose estimation, publication bias, and possible alternative hypotheses (eg, confounding by total vegetable consumption) preclude sole reliance on summary effect estimates. Publication Types: Meta-Analysis
8. Gandini S, Merzenich H, Robertson C, Boyle P. Eur J Cancer 2000 Mar;36(5):636-46. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients. Div of Epidemiology and Biostatics, European Inst of Oncology, Via Ripamonti 435, 20141, Milan, Italy. [email protected] A meta-analysis was carried out, in order to summarise published data on the relationship between breast cancer, fruit and vegetable consumption and/or the intake of beta-carotene and vitamin C. Relative risks were extracted from 26 published studies from 1982 to 1997. Random and fixed effects models were used. Between studies, heterogeneity was found for vegetables, fruit, vitamin C but not for beta-carotene. Summary relative risk (RR) estimates based upon a random effects model, except for beta-carotene, for 'high consumption' compared with 'low consumption', derived from the studies satisfying the inclusion criteria were as follows: vegetable consumption: RR=0.75 (95% CI (confidence interval) 0.66-0.85) from 17 studies; fruit consumption: RR=0.94 (95% CI 0.79-1.11) from 12 studies; vitamin C: RR=0.80 (95% CI 0.68-0.95) from 9 studies; beta-carotene: RR=0.82 (95% CI 0.76-0.91) from 11 studies. This analysis confirms the association between intake of vegetables and, to a lesser extent, fruits and breast cancer risk from published sources. Increasing vegetable consumption might reduce the risk of breast cancer. Publication Types: Meta-Analysis
9. Garrison MM, Christakis DA. Pediatrics 2000 Jul;106(1 Pt 2):184-90. A systematic review of treatments for infant colic. Child Health Inst, Univ of Washington, Seattle, USA. OBJECTIVE: To conduct a systematic review of rigorously evaluated treatments for infant colic. METHODS. Online bibliographic databases were searched for the term "colic" in articles classified as clinical trials or randomised controlled trials and conducted in infants. Reference lists from review articles, meta-analyses, and the selected articles were also reviewed for potential studies. The abstracts or full-text articles of 57 relevant studies were examined, of which 22 met the selection criteria. The methodology and findings of all retrieved articles were critically evaluated. Data were extracted from each article regarding study methods, intervention studied, outcomes measured, and results. RESULTS. Four of the interventions studied had data of adequate quality and statistically significant numbers needed to treat (NNT): hypoallergenic diet (NNT=6), soy formula (NNT=2), reduced stimulation (NNT=2), and herbal tea (NNT=3). CONCLUSION: There are some effective therapies for infant colic, but additional rigorous studies of existing and alternative therapies are needed. Publication Types: Meta-Analysis
10. Gore SM, Fontaine O, Pierce NF. BMJ 1992 Feb 1;304(6822):287-91. Comment in: BMJ. 1992 Apr 11;304(6832):982. Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials. Medical Research Council, Biostatistics Unit, Cambridge. OBJECTIVE: To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN: Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS: The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION: Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES: Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS: The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSION: The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged. Publication Types: Meta-Analysis
11. Harrer G, Schulz V. J Geriatr Psychiatry Neurol 1994 Oct;7 Suppl 1:S6-8. Clinical investigation of the antidepressant effectiveness of hypericum. Institut fur Forensische Psychiatrie, Universitat, Salzburg, Austria. To date, 25 controlled therapy studies have investigated the antidepressive effectiveness of hypericum extracts. A total of 1592 treatment cases have been included. The dosage was typically 300 to 900 mg total extract daily; the therapy duration was 2 to 6 weeks. Fifteen studies were performed comparing hypericum extracts with placebo, 10 studies as comparative studies. This paper presents an overview of their results. Publication Types: Meta-Analysis
12. Hippius H. Curr Med Res Opin 1998;14(3):171-84. St John's Wort (Hypericum perforatum): a herbal antidepressant. Dept of Psychiatry, Univ of Munich, Germany. A number of clinical studies in the past few years have indicated that whole extract of St John's wort (Hypericum perforatum L.) has antidepressant effects. St John's wort offers promising results in the treatment of patients with mild and moderate depression (response rate of 60-70% estimated by analysis of pooled data). St John's wort preparations are well tolerated. Their use rarely leads to adverse reactions which, when they do occur, are mainly subjective symptoms (e.g. gastrointestinal, dizziness). The generally good tolerability of St John's wort preparations and the resulting high patient compliance in taking the prescribed medication, in conjunction with their efficacy in mild and moderate depression, make these preparations particularly suitable for use in outpatient practice. Tolerability is also very good in elderly patients. If a sufficiently high-dose course of treatment with St John's wort preparations (900 mg daily) does not lead to a clear improvement in depression after four to six weeks, therapy should be continued with an established ('classical') antidepressant. Publication Types: Meta-Analysis
13. Hopfenmuller W. Arzneimittelforschung 1994 Sep;44(9):1005-13. [Evidence for a therapeutic effect of Ginkgo biloba special extract. Meta-analysis of 11 clinical studies in patients with cerebrovascular insufficiency in old age.] [Article in German] Institut fur Medizinische Statistik und Informationsverarbeitung, Freien Universitat Berlin, Klinikum Steglitz. Eleven controlled clinical trials were evaluated in a meta-analysis in order to proof the effectiveness of the ginkgo biloba special extract LI 1370 (Kaveri forte). All included studies were placebo controlled randomised double blind studies, using in most of the cases a daily dosage of 150 mg extract. The requirements for the quality of the studies were the basic criteria for the performance of clinical drug tests analysed from the biometrical scope. The analysis of the individual studies revealed that three studies had to be excluded from the meta-analysis according to methodological or objective reasons. In two further studies the evaluation of the physician or the patients was missing, therefore the studies could not be used for the analysis of the "global effectiveness". All other studies were comparable with regard to diagnoses, inclusion and exclusion criteria as well as methodology. Therefore a statistical meta-analysis could be performed for them, analysing the parameters "single symptoms", total score of clinical symptoms and "global effectiveness". Conclusion: For all analysed single symptoms significant differences could be concluded, indicating the superiority of ginkgo biloba in comparison to placebo. The analysis of the total score of clinical symptoms from all relevant studies indicated that 7 studies confirmed the effectiveness (Ginkgo biloba being better compared to placebo) while only one study was inconclusive (the medications were not different). This relation confirms the therapeutical effectiveness of ginkgo biloba regarding the clinical symptom complex. Finally the parameter "global effectiveness" was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) Publication Types: Clinical Trial Controlled Clinical Trial Meta-Analysis Randomised Controlled Trial
14. Hu FB, Stampfer MJ. Curr Atheroscler Rep 1999 Nov;1(3):204-9. Nut consumption and risk of coronary heart disease: a review of epidemiologic evidence. Dept of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Traditionally nuts have been perceived as an unhealthy food because of their high fat content. However, recent accumulative evidence suggests that frequent consumption of nuts may be protective against coronary heart disease (CHD). So far, five large prospective cohort studies (the Adventist Health Study, the Iowa Women Health Study, the Nurses' Health Study, the Physicians' Health Study, and the CARE Study) have examined the relation between nut consumption and the risk of CHD and all have found an inverse association. In addition, several clinical studies have observed beneficial effects of diets high in nuts (including walnuts, peanuts, almonds, and other nuts) on blood lipids. The beneficial effects of nut consumption observed in clinical and epidemiologic studies underscore the importance of distinguishing different types of fat. Most fats in nuts are mono- and polyunsaturated fats that lower low-density lipoprotein cholesterol level. Based on the data from the Nurses' Health Study, we estimated that substitution of the fat from 1 ounce of nuts for equivalent energy from carbohydrate in an average diet was associated with a 30% reduction in CHD risk and the substitution of nut fat for saturated fat was associated with 45% reduction in risk. Given the strong scientific evidence for the beneficial effects of nuts, it seems justifiable to move nuts to a more prominent place in the USDA Food Guide Pyramid. Regular nut consumption can be recommended in the context of a healthy and balanced diet. Publication Types: Meta-Analysis
15. Ishani A, MacDonald R, Nelson D, Rutks I, Wilt TJ. Am J Med 2000 Dec 1;109(8):654-64. Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis. Minneapolis Veterans Affairs Ctr for Chronic Disease Outcomes Research and the VA Coordinating Ctr for the Cochrane Review Group in Prostate Diseases and Urologic Malignancies, Minneapolis, Minnesota, USA. PURPOSE: To conduct a systematic review and quantitative meta-analysis of the therapeutic efficacy and tolerability of Pygeum africanum in men with symptomatic benign prostatic hyperplasia. METHODS: Studies were identified through the search of Medline (1966 to 2000), Embase, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. Randomised trials were included if participants had symptomatic benign prostatic hyperplasia, the intervention was a preparation of P. africanum alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacologic therapies for benign prostatic hyperplasia, and treatment duration was at least 30 days. Two investigators independently extracted key data on design features, subject characteristics, and therapy allocation. RESULTS: A total of 18 randomised controlled trials involving 1,562 men met the inclusion criteria and were analysed. Many studies did not report results in a method that permitted meta-analysis. Only 1 of the studies reported a method of treatment allocation concealment, although 17 were double-blinded. The mean study duration was 64 days (range 30 to 122). Compared with placebo in 6 studies, P. africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome (-0.8 SD [95% confidence interval (CI): -1.4 to -0.3]). Summary estimates of individual outcomes were also improved by P. africanum. Men were more than twice as likely to report an improvement in overall symptoms (risk ratio=2.1, 95% CI: 1.40 to 3.1). Nocturia was reduced by 19% and residual urine volume by 24%; peak urine flow was increased by 23%. Adverse effects due to P. africanum were mild and similar to placebo. The overall dropout rate was 12% and was similar for P. africanum (13%), placebo (11%), and other controls (8%; P=0.4 versus placebo and P=0.5 versus other controls).CONCLUSION: The literature is limited by the short duration of studies and the variability in study design, the use of phytotherapeutic preparations, and the types of reported outcomes. However, the evidence suggests that P. africanum modestly, but significantly, improves urologic symptoms and flow measures. Further research is needed using standardised preparations of P. africanum to determine its long-term effectiveness and ability to prevent complications associated with benign prostatic hyperplasia. Publication Types: Meta-Analysis
16. Kim HL, Streltzer J, Goebert D. J Nerv Ment Dis 1999 Sep;187(9):532-8. St. John's wort for depression: a meta-analysis of well-defined clinical trials. Dept of Psychiatry, Univ of Hawaii, John A. Burns School of Medicine, Honolulu 96813, USA. Studies concluding that St. John's wort (Hypericum perforatum) is an effective antidepressant can be challenged due to questionable methodology. We attempt to correct this by a meta-analysis utilizing only well-defined clinical trials. Controlled, double-blind studies using strictly defined depression criteria were analysed by the rate of change of depression and by the number of "treatment responders." Rates of side effects and dropouts were also analysed. Hypericum was 1.5 times more likely to result in an antidepressant response than placebo and was equivalent to tricyclic antidepressants (TCAs). There was a higher dropout rate in the TCA group and the TCAs were nearly twice as likely to cause side effects, including those more severe than hypericum. Hypericum perforatum was more effective than placebo and similar in effectiveness to low-dose TCAs in the short-term treatment of mild to moderately severe depression. However, design problems in existing studies prevent definitively concluding that St. John's wort is an effective antidepressant. Publication Types: Meta-Analysis
17. Klepser TB, Klepser ME. Am J Health Syst Pharm 1999 Jan 15;56(2):125-38; quiz 139-41. Unsafe and potentially safe herbal therapies. Div of Clinical and Administrative Pharmacy, College of Pharmacy, The Univ of Iowa, Iowa City 52242, USA. [email protected] Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the USA, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and mahuang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results suggest efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available. Publication Types: Meta-Analysis
18. Law MR, Morris JK. Dept of Environmental and Preventive Medicine, Wolfson Inst of Preventive Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry. Eur J Clin Nutr 1998 Aug;52(8):549-56. By how much does fruit and vegetable consumption reduce the risk of ischaemic heart disease? OBJECTIVE: To quantify the relationship between fruit and vegetable consumption and the incidence of ischaemic heart disease. DESIGN: A meta-analysis of cohort studies of the relationship between ischaemic heart disease and markers of fruit and vegetable consumption, namely dietary intake of fruit, vegetables, carotenoids, vitamin C, fruit fibre and vegetable fibre, and serum concentration of carotenoids and vitamin C, adjusted for other risk factors. MAIN OUTCOME MEASURES: Risk of ischaemic heart disease at the 90th centile of consumption relative to that at the 10th, equivalent to about a four-fold difference in fruit consumption and a doubling of vegetable consumption. RESULTS: The association with ischaemic heart disease was of similar magnitude for all six dietary markers of fruit and vegetable consumption. The median of the six estimates was that risk was 15% (range 12-19%) lower at the 90th centile of consumption than at the 10th. The estimates were generally adjusted for the possible confounding effect of other heart disease risk factors. The serum studies of vitamin C were consistent with this; those of carotenoids suggested a larger difference (43%) but were not adjusted for the important confounding effect of smoking. The substances in fruit and vegetables responsible for the protective effect on heart disease are uncertain but the effect is commensurate with the estimated protective effects of the potassium and folate in fruit and vegetables. Beta-carotene or vitamin E are not likely to be important because randomised trials of these vitamins in large doses have shown no reduction in heart disease mortality. CONCLUSION: The risk of ischaemic heart disease is about 15% lower at the 90th than the 10th centile of fruit and vegetable consumption. Publication Types: Meta-Analysis
19. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. BMJ 1996 Aug 3;313(7052):253-8. Comment in: BMJ. 1996 Aug 3;313(7052):241-2. BMJ. 1996 Nov 9;313(7066):1204-5. St John's wort for depression: an overview and meta-analysis of randomised clinical trials. Projekt Munchener Modell, Ludwig-Maximilians-Universitat, Munich, Germany. OBJECTIVE: To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. DESIGN: Systematic review and meta-analysis of trials revealed by searches. TRIALS: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. MAIN OUTCOME MEASURES: A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. RESULTS: Hypericum extracts were significantly superior to placebo (ratio=2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. CONCLUSION: There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed. Publication Types: Meta-Analysis
20. Lipworth L, Martinez ME, Angell J, Hsieh CC, Trichopoulos D. Prev Med 1997 Mar-Apr;26(2):181-90. Olive oil and human cancer: an assessment of the evidence. Harvard Ctr for Cancer Prevention, Harvard School of Public Health, Boston, Massachusetts 02115, USA. BACKGROUND: We have attempted to summarize the evidence concerning the association of olive oil intake with cancer risk in humans. METHODS: We reviewed all the studies that met the following criteria: (1) they have directly examined olive oil in the context of an extensive food frequency questionnaire or have evaluated the role of monounsaturated fat in populations of Mediterranean countries where a large fraction of monounsaturated fat originates from olive oil and (2) they have analysed the data with explicit or implicit control for energy intake to accommodate the likely confounding influence of caloric consumption and to account to a certain extent for differential completeness of reporting between cases and controls. Ecologic studies were also considered and relevant experimental data were invoked. RESULTS: With respect to breast cancer, there is converging evidence for a protective effect, although the data are not definitive. For other cancer types, the overall epidemiologic evidence, although promising, is quantitatively limited and qualitatively suboptimal. CONCLUSION: The issue is of major public health importance and deserves additional study. Publication Types: Meta-Analysis
21. Ludtke R, Wiesenauer M. Wien Med Wochenschr 1997;147(14):323-7. [A meta-analysis of homeopathic treatment of pollinosis with Galphimia glauca.] [Article in German] Institut fur Medizinische Informationsverarbeitung, Tubingen, Deutschland. [email protected] OBJECTIVE: 1) To assess the efficacy of homeopathic prepared Galphimia glauca compared to placebo in the treatment of pollinosis. 2) To estimate the corresponding overall success rate of Galphimia glauca. Meta-analysis of clinical trials. STUDY SELECTION: 7 randomised double-blind placebo-controlled trials and 4 not placebo-controlled trials (1 randomised and controlled, 1 prospective uncontrolled, 2 retrospective uncontrolled) performed by our study group between 1980 and 1989. An additional MEDLINE search revealed no further trials on this topic. Exclusion and inclusion criteria were identical over all trials. In total, 1038 ambulatory patients that suffered from acute pollinosis (752 in placebo-controlled trials) entered the analysis. MAIN OUTCOME MEASURES: Relative frequency and relative risk for showing noticeable and soothing relief in ocular symptoms as assessed by the patient. The overall rate of improved eye-symptoms is about 1.25 (CI: 1.09 to 1.43) times higher in the verum than in the placebo group. Verum success rate is estimated by 79.3% (CI: 74.1% to 85.0%). Across the single studies the results were highly comparable except for the study run in 1985. A significant superiority of Galphimia glauca over placebo is demonstrated. Estimates of verum success rates are comparable with those of conventional antihistaminics, but no side effects occurred. As not all of the single studies were analysed by intention to treat analysis the results may be biased. Publication Types: Meta-Analysis
22. Olson BH, Anderson SM, Becker MP, Anderson JW, Hunninghake DB, Jenkins DJ, LaRosa JC, Rippe JM, Roberts DC, Stoy DB, Summerbell CD, Truswell AS, Wolever TM, Morris DH, Fulgoni VL 3rd. Kellogg Company, Science and Technology Ctr, Battle Creek, MI 49016-3423, USA. J Nutr 1997 Oct;127(10):1973-80. Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis. We conducted a meta-analysis to determine the effect of consumption of psyllium-enriched cereal products on blood total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels and to estimate the magnitude of the effect among 404 adults with mild to moderate hypercholesterolemia (TC of 5.17-7.8 mmol/L) who consumed a low fat diet. Studies of psyllium cereals were identified by a computerized search of MEDLINE and Current Contents and by contacting USA-based food companies involved in psyllium research. Published and unpublished studies were reviewed by one author and considered eligible for inclusion in the meta-analysis if they were conducted in humans, were randomised, controlled experiments, and included a control group that ate cereal providing </=3 g soluble fibre/d. Eight published and four unpublished studies, conducted in four countries, met the criteria. Analysis of a linear model was performed, controlling for sex and age. Female subjects were divided into two groups to provide a rough estimate of the effect of menopausal status (premenopausal=<50 y, postmenopausal=>/=50 y) on blood lipids. The meta-analysis showed that subjects who consumed a psyllium cereal had lower TC and LDL-C concentrations [differences of 0.31 mmol/L (5%) and 0.35 mmol/L (9%), respectively] than subjects who ate a control cereal; HDL-C concentrations were unaffected in subjects eating psyllium cereal. There was no effect of sex, age or menopausal status on blood lipids. Conclusion: consuming a psyllium-enriched cereal as part of a low fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low fat diet alone. Publication Types: Meta-Analysis
23. Peters U, Poole C, Arab L. Am J Epidemiol 2001 Sep 15;154(6):495-503. Does tea affect cardiovascular disease? A meta-analysis. Dept of Epidemiology, Univ of North Carolina School of Public Health, Chapel Hill, NC 27599-7400, USA. This meta-analysis of tea consumption in relation to stroke, myocardial infarction, and all coronary heart disease is based on 10 cohort studies and seven case-control studies. The study-specific effect estimates for stroke and coronary heart disease were too heterogeneous to be summarized (homogeneity p<0.02 for stroke, p<0.001 for coronary heart disease). Only the relative risk estimates for myocardial infarction (seven studies) appeared reasonably homogeneous (homogeneity p=0.20). The incidence rate of myocardial infarction is estimated to decrease by 11% with an increase in tea consumption of 3 cups per day (fixed-effects relative risk estimate=0.89, 95% confidence interval: 0.79, 1.01) (1 cup=237 ml). However, evidence of bias toward preferential publication of smaller studies that suggest protective effects urges caution in interpreting this result. The geographic region where the studies were conducted appeared to explain much of the heterogeneity among coronary heart disease, myocardial infarction, and probably stroke results. With increasing tea consumption, the risk increased for coronary heart disease in the United Kingdom and for stroke in Australia, whereas the risk decreased in other regions, particularly in continental Europe. Publication Types: Meta-Analysis
24. Pittler MH, Ernst E. Am J Gastroenterol 1998 Jul;93(7):1131-5. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Dept of Complementary Medicine, Postgraduate Medical School, Univ of Exeter, United Kingdom. OBJECTIVE: Peppermint oil is the major constituent of several over-the-counter remedies for symptoms of irritable bowel syndrome (IBS). As the etiology of IBS is not known and treatment is symptomatic, there is a ready market for such products. However, evidence to support their use is sparse. The aim of this study was to review the clinical trials of extracts of peppermint (Mentha X piperita L.) as a symptomatic treatment for IBS. METHODS: Computerized literature searches were performed to identify all randomised controlled trials of peppermint oil for IBS. Databases included Medline, Embase, Biosis, CISCOM, and the Cochrane Library. There were no restrictions on the language of publication. Data were extracted in a standardised, predefined fashion, independently by both authors. Five double blind, randomised, controlled trials were entered into a metaanalysis. RESULTS: Eight randomised, controlled trials were located. Collectively they indicate that peppermint oil could be efficacious for symptom relief in IBS. A metaanalysis of five placebo-controlled, double blind trials seems to support this notion. In view of the methodological flaws associated with most studies, no definitive judgment about efficacy can be given. CONCLUSION: The role of peppermint oil in the symptomatic treatment of IBS has so far not been established beyond reasonable doubt. Well designed and carefully executed studies are needed to clarify the issue. Publication Types: Meta-Analysis
25. Pittler MH, Ernst E. Dept of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, Univ of Exeter, United Kingdom. Am J Med 2000 Mar;108(4):276-81. Comment in: Am J Med. 2000 Mar;108(4):341-2. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomised trials. PURPOSE: The optimal treatment of intermittent claudication has not yet been identified. Ginkgo biloba extract has been reported to have beneficial effects. We performed a meta-analysis of the efficacy of Ginkgo biloba extract for intermittent claudication based on the results of randomised, placebo-controlled, double-blind trials. METHODS: Literature searches of MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library were performed to identify studies on the topic. Manufacturers of commercial Ginkgo biloba products and authors of original publications and reviews were contacted to provide additional information. No language restrictions were imposed. RESULTS: Eight randomised, placebo-controlled, double-blind trials were included. Meta-analysis found a significant difference in the increase in pain-free walking distance in favor of Ginkgo biloba (weighted mean difference: 34 meters, 95% confidence interval [CI]: 26 to 43 meters). In studies using similar methodological features (ergometer speed: 3 km/h, inclination: 12%) this difference was 33 meters in favor of Ginkgo biloba (95% CI: 22 to 43 meters). Adverse effects were rare, mild, and transient. CONCLUSION: Ginkgo biloba extract is superior to placebo in the symptomatic treatment of intermittent claudication. However, the size of the overall treatment effect is modest and of uncertain clinical relevance. Publication Types: Meta-Analysis
26. Pittler MH, Ernst E. J Clin Psychopharmacol 2000 Feb;20(1):84-9. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. Dept of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, Univ of Exeter, United Kingdom. [email protected] Synthetic anxiolytic drugs are effective for treating anxiety, but they are burdened with adverse effects. Constraints on resources and time often render therapies such as psychologic interventions impracticable. Thus, an effective oral medication with few adverse effects would be a welcome addition to the therapeutic repertoire. This systematic review and meta-analysis was aimed at assessing the evidence for or against the efficacy of kava extract as a symptomatic treatment for anxiety. Systematic literature searches were performed in the computerized databases MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library (all from their respective inception to June 1998). The search terms used were kava, kawa, kavain, Piper methysticum, and Rauschpfeffer (German term for Piper methysticum). Experts on the subject were contacted to provide further information. There were no restrictions regarding the language of publication. Double-blind, randomised, placebo-controlled trials of oral kava extract for the treatment of anxiety were included. All publications were blinded before assessment by a person not involved in the study. Data were extracted in a standardised, predefined fashion independently by the two reviewers. The methodologic quality of all trials was assessed. Superiority of kava extract over placebo was suggested by all seven reviewed trials. The meta-analysis of three trials suggests a significant difference in the reduction of the total score on the Hamilton Rating Scale for Anxiety in favor of kava extract (weighted mean difference, 9.69; 95% confidence interval, 3.54-15.83). Conclusion: Kava extract is superior to placebo as a symptomatic treatment for anxiety. Therefore, kava extract is an herbal treatment option for anxiety that is worthy of consideration. Publication Types: Meta-Analysis
27. Ross RN, Nelson HS, Finegold I. Clin Ther 2000 Mar;22(3):329-41. Effectiveness of specific immunotherapy in the treatment of asthma: a meta-analysis of prospective, randomised, double-blind, placebo-controlled studies. Medical/Science Analytics, Brookline, Massachusetts 02445, USA. BACKGROUND: Despite decades of positive experience with specific immunotherapy (SIT) in the treatment of asthma, outcomes associated with SIT have not been evaluated. Objective: This meta-analysis was conducted to compare the effects of SIT plus medical treatment with those of SIT without medical treatment in patients with asthma. METHODS: All studies of SIT in patients with asthma published in English between the years 1966 and 1998 were identified through a MEDLINE search. All prospective, randomised, double-blind, placebo-controlled studies of SIT identified by the search were included in the meta-analysis. One author (R.N.R.) extracted data from these studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Data were extracted from 24 identified studies of the clinical effectiveness of SIT in the treatment of asthma, involving 962 asthmatic patients with documented allergy. Immunotherapy was judged effective in 17 (71%) of the 24 studies, ineffective in 4 (17%), and equivocal in 3 (12%) (chi2=15.25, df=2, P=0.0005). Symptoms of asthma were more likely to improve in patients who received SIT than in patients who received placebo (OR 2.76, 95% CI 2.22 to 3.42). Results also favored the immunotherapy group for improvement in pulmonary function (OR 2.87, 95% CI 1.82 to 4.52), protection against bronchial challenge (OR 1.81, 95% CI 1.32 to 2.49), and reduced need for medications (OR 2.00, 95% CI 1.46 to 2.72). CONCLUSION: The findings of this meta-analysis support the conclusion that SIT is effective in a population of patients with allergen-triggered asthma. Publication Types: Meta-Analysis
28. Ross RN, Nelson HS, Finegold I. Clin Ther 2000 Mar;22(3):342-50. Effectiveness of specific immunotherapy in the treatment of allergic rhinitis: an analysis of randomised, prospective, single- or double-blind, placebo-controlled studies. Medical/Science Analytics, Brookline, Massachusetts, 02445, USA. BACKGROUND: The effectiveness of specific immunotherapy (SIT) in the treatment of allergic rhinitis has been supported by empirical evidence and clinical experience. OBJECTIVE: This report is an analysis of multiple studies involving patients with documented allergic rhinitis. METHODS: All studies of the effectiveness of SIT in the treatment of allergic rhinitis published in English between the years 1966 and 1996 were identified through a MEDLINE search. All prospective, single- or double-blind, placebo-controlled studies were included in the analysis. One author (R.N.R.) extracted data from the studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model for a variety of clinical measures in studies that permitted the extraction of numbers of patients with positive and negative outcomes. RESULTS: Data were extracted from 16 studies of the clinical effectiveness of SIT in the treatment of allergic rhinitis, involving 759 patients (546 adults, 53 children, 160 all ages). In 15 (94%) of the studies, investigators concluded that SIT was effective. In the remaining study (the only one conducted in children), investigators concluded that SIT was not effective. Symptoms of allergic rhinitis were more likely to improve in patients receiving SIT than in the comparison patients (OR 1.81, 95% CI 1.48 to 2.23). Symptom-medication scores were significantly lower in patients receiving SIT than in the comparison patients in all studies using such measures (P<0.05). CONCLUSION: Results of this analysis support the conclusion that SIT is effective in the treatment of allergic rhinitis. Publication Types: Meta-Analysis
29. Schneider B. Institut fur Biometrie, Medizinische Hochschule Hannover. Arzneimittelforschung 1992 Apr;42(4):428-36. [Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies.] [Article in German] Meta-analysis was applied to controlled clinical trials with Ginkgo biloba extract EGb 761 in patients with peripheral arterial disease. Included were 5 placebo-controlled clinical trials with similar design and inclusion criteria. In all studies treatment effect was quantified by the increase of walking distance (measured in standardised treadmill exercise). The effect value of EGb 761 treatment was expressed by the standardised mean difference in walking distance increase between EGb 761 and placebo, standardised by the standard deviation. It could be shown that this effect value is homogeneous in all trials. The global effect size was estimated as 0.75. This means that the mean increase in walking distance achieved by EGb 761 is 0.75 times of the standard deviation higher than that achieved by placebo. This value is highly significant different from zero. Conclusion: Meta-analysis revealed a highly significant therapeutic effect of EGb 761 for the treatment of peripheral arterial disease. Publication Types: Meta-Analysis
30. Silagy C, Neil A. J R Coll Physicians Lond 1994 Jan-Feb;28(1):39-45. Garlic as a lipid lowering agent: a meta-analysis. Dept of Public Health and Primary Care, Univ of Oxford. Garlic supplements may have an important role to play in the treatment of hypercholesterolaemia. To determine the effect of garlic on serum lipids and lipoproteins relative to placebo and other lipid lowering agents, a systematic review, including meta-analysis, was undertaken of published and unpublished randomised controlled trials of garlic preparations of at least four weeks' duration. Studies were identified by a search of MEDLINE and the ALTERNATIVE MEDICINE electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. Sixteen trials, with data from 952 subjects, were included in the analyses. Many of the trials had methodological shortcomings. The pooled mean difference in the absolute change (from baseline to final measurement in mmol/l) of total serum cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol was compared between subjects treated with garlic therapy against those treated with placebo or other agents. The mean difference in reduction of total cholesterol between garlic-treated subjects and those receiving placebo (or avoiding garlic in their diet) was -0.77 mmol/l (95% CI: -0.65, -0.89 mmol/l). There was a 12% reduction in total cholesterol with garlic therapy beyond the final levels achieved with placebo alone. The reduction was evident after one month of therapy and persisted for at least six months. In the dried garlic powders, in which the allicin content is standardised, there was no significant difference in the size of the reduction across the dose range of 600-900 mg daily. Dried garlic powder preparations also significantly lowered serum triglyceride by 0.31 mmol/l compared to placebo (95% CI: -0.14, -0.49). (ABSTRACT TRUNCATED AT 250 WORDS) Publication Types: Meta-Analysis
31. Silagy CA, Neil HA. Dept of General Practice, Flinders Univ of South Australia, Adelaide. J Hypertens 1994 Apr;12(4):463-8. A meta-analysis of the effect of garlic on blood pressure. OBJECTIVE: To undertake a systematic review, including meta-analysis, of published and unpublished randomised controlled trials of garlic preparations to determine the effect of garlic on blood pressure relative to placebo and other antihypertensive agents. DATA IDENTIFICATION: Studies were identified by a search of Medline and the Alternative Medicine electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. STUDY SELECTION: Only randomised controlled trials of garlic preparations that were at least 4 weeks in duration were deemed eligible for inclusion in the review. DATA EXTRACTION: Data were extracted from the published reports by the two authors independently, with disagreements resolved by discussion. RESULTS: Eight trials were identified (all using the same dried garlic powder preparation (Kwai) with data from 415 subjects included in the analyses. Only three of the trials were specifically conducted in hypertensive subjects, and many had other methodological shortcomings. Of the seven trials that compared the effect of garlic with that of placebo, three showed a significant reduction in systolic blood pressure (SBP) and four in diastolic blood pressure (DBP). The overall pooled mean difference in the absolute change (from baseline to final measurement) of SBP was greater in the subjects who were treated with garlic then in those treated with placebo. For DBP the corresponding reduction in the garlic-treated subjects was slightly smaller. CONCLUSION: Garlic may be of some clinical use in subjects with mild hypertension. However, there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects. More-rigorously designed and analysed trials are needed. Publication Types: Meta-Analysis
32. Steinmaus CM, Nunez S, Smith AH. Am J Epidemiol 2000 Apr 1;151(7):693-702. Diet and bladder cancer: a meta-analysis of six dietary variables. Div of Occupational and Environmental Medicine, Univ of California at San Francisco, USA. In 1996, >300,000 new cases of bladder cancer were diagnosed worldwide. Besides tobacco smoking, occupation, and other factors, diet may play a role in causation of this illness. The authors performed a meta-analytical review of epidemiologic studies linking six dietary factors to bladder cancer. These factors include retinol, beta-carotene, fruits, vegetables, meat, and fat. Increased risks of bladder cancer were associated with diets low in fruit intake (relative risk (RR)=1.40, 95% confidence interval (CI): 1.08, 1.83), and slightly increased risks were associated with diets low in vegetable intake (RR=1.16, 95% CI: 1.01, 1.34). Elevated risks were identified for diets high in fat intake (RR=1.37, 95% CI: 1.16, 1.62) but not for diets high in meat intake (RR=1.08, 95% CI: 0.82, 1.42). No increased risks were found for diets low in retinol (RR=1.01, 95% CI: 0.83, 1.23) or beta-carotene (RR=1.10, 95% CI: 0.93, 1.30) intake. Conclusion: Diet high in fruits and vegetables and low in fat intake may help prevent bladder cancer, but the individual dietary constituents that reduce the risks remain unknown. Publication Types: Meta-Analysis
33. Steinmetz KA, Potter JD. Cancer Causes Control 1991 Sep;2(5):325-57. Vegetables, fruit, and cancer. I. Epidemiology. Div of Epidemiology, School of Public Health, Univ of Minnesota, Minneapolis 55455. The epidemiologic literature on the relationship between vegetable and fruit consumption and human cancer at a variety of sites is reviewed systematically. A total of 13 ecologic studies, nine cohort studies, and 115 case-control studies are included. Cancer of all sites, cancers of lung, breast, colon, rectum, esophagus, larynx, oral cavity and pharynx, stomach, pancreas, prostate, bladder, ovary, endometrium, cervix, and thyroid, as well as mesothelioma and gestational trophoblastic disease, are considered. Relevant data from clinical trials, animal, and in vitro studies are included. Conclusion: Consumption of higher levels of vegetables and fruit is associated consistently, although not universally, with a reduced risk of cancer at most sites. The association is most marked for epithelial cancers: particularly those of the alimentary and respiratory tracts: and, currently, is weak to nonexistent for hormone-related cancers. The association exists for a wide variety of vegetables and fruit with some suggestion that raw forms are associated most consistently with lower risk. Possible mechanisms by which vegetable and fruit intake might alter risk of cancer and possible adverse effects of vegetable and fruit consumption will be considered in Part II of this review. Publication Types: Meta-Analysis
34. Stevinson C, Pittler MH, Ernst E. Ann Intern Med 2000 Sep 19;133(6):420-9. Garlic for treating hypercholesterolemia. A meta-analysis of randomised clinical trials. Dept of Complementary Medicine, Univ of Exeter, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom. PURPOSE: To investigate the effect of garlic on total cholesterol level in persons with elevated levels by conducting a meta-analysis of randomised, double-blind, placebo-controlled trials. DATA SOURCES: Systematic literature searches were conducted on the MEDLINE, EMBASE, BIOSIS, Cochrane Library, AMED, and CISCOM databases. Manufacturers of commercial garlic preparations and experts in the field were asked about published or unpublished trials. STUDY SELECTION: Selected trials were required to state that they were randomised, double-blind, and placebo-controlled; use garlic monopreparations; include persons with mean total cholesterol levels of at least 5.17 mmol/L (200 mg/dL); and report total cholesterol level as an end point. There were no language restrictions. DATA EXTRACTION: Two reviewers, blinded to key identifiers of each paper, independently extracted data in a standardised manner and assessed methodologic quality by using the Jadad scale. Discrepancies were settled through discussion. DATA SYNTHESIS: In the 13 trials included in the meta-analysis, garlic reduced total cholesterol level from baseline significantly more than placebo (P<0.01); the weighted mean difference was -0.41 mmol/L (95% CI, -0.66 to -0.15 mmol/L) (-15.7 mg/dL [CI, -25.6 to -5. 7 mg/dL]). Six diet-controlled trials with the highest scores for methodologic quality revealed a nonsignificant difference between garlic and placebo groups; the weighted mean difference was -0.11 mmol/L (CI, -0.30 to 0.08 mmol/L) (-4.3 mg/dL [CI, -11.7 to 3.1 mg/dL]). CONCLUSION: The available data suggest that garlic is superior to placebo in reducing total cholesterol levels. However, the size of the effect is modest, and the robustness of the effect is debatable. The use of garlic for hypercholesterolemia is therefore of questionable value. Publication Types: Meta-Analysis Review Review, Academic
35. Trock B, Lanza E, Greenwald P. J Natl Cancer Inst 1990 Apr 18;82(8):650-61. Dietary fibre, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence. Fox Chase Cancer Ctr, Philadelphia, PA. Whether colon cancer risk can be modified by a diet rich in vegetables, grains, and fruit, and, if so, whether the protective factor is dietary fibre or other biologically active components correlated with a high-fibre diet are questions of active research interest. Because studies on diet are susceptible to bias from a number of sources, in this review we evaluated the adequacy of study methodology as well as study results to clarify how much protection, if any, is conferred by a high-fibre diet. The review consisted of an aggregate assessment of the strength of evidence from 37 observational epidemiologic studies as well as meta-analyses of data from 16 of the 23 case-control studies. Both types of analyses revealed that most studies gave support for a protective effect associated with fibre-rich diets; an estimated combined odds ratio (OR) of 0.57 (95% confidence interval=0.50, 0.64) was obtained when the highest and lowest quantiles of intake were compared. Risk estimates based on vegetable consumption (OR=0.48) were only slightly more convincing than those based on an estimate of fibre intake (OR=0.58), but the data do not permit discrimination between effects due to fibre and nonfiber effects due to vegetables. Publication Types: Meta-Analysis
36. Warshafsky S, Kamer RS, Sivak SL. Ann Intern Med 1993 Oct 1;119(7 Pt 1):599-605. Comment in: Ann Intern Med. 1993 Oct 1;119(7 Pt 1):627-8. Ann Intern Med. 1994 Jun 1;120(11):969-70. Effect of garlic on total serum cholesterol. A meta-analysis. Dept of Medicine, New York Medical College, Valhalla 10595. OBJECTIVE: To assess the size and consistency of garlic's effect on total serum cholesterol in persons with cholesterol levels greater than 5.17 mmol/L (200 mg/dL). DATA SOURCES: Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of the bibliographies of published studies and reviews. STUDY SELECTION: Trials were selected if they were randomised and placebo-controlled and if at least 75% of their patients had cholesterol levels greater than 5.17 mmol/L (200 mg/dL). Studies were excluded if they did not provide enough data to compute effect size. Five of 28 studies were selected for review. DATA EXTRACTION: Details of study design, patient characteristics, interventions, duration of therapy, and cholesterol measurements were extracted by one author and were verified by another. DATA SYNTHESIS: Study quality was evaluated by multiple reviewers using a closed-ended questionnaire. Patients treated with garlic consistently showed a greater decrease in total cholesterol levels compared with those receiving placebo. Meta-analysis of homogeneous trials estimated a net cholesterol decrease attributable to garlic of 0.59 mmol/L (95% CI, 0.44 to 0.74) (23 mg/dL [CI, 17 to 29]) (P<0.001). CONCLUSION: Meta-analysis of the controlled trials showed a significant reduction in total cholesterol levels. The best available evidence suggests that garlic, in an amount approximating one half to one clove per day, decreased total serum cholesterol levels by about 9% in the groups of patients studied. Publication Types: Meta-Analysis
37. Wettstein A. Phytomedicine 2000 Jan;6(6):393-401. Cholinesterase inhibitors and Gingko extracts: are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months' duration. Stadtarztlicher Dienst, Zurich. [email protected] The efficacy of four cholinesterase inhibitors (tacrine, donepezil, rivastigmine, metrifonate) and Ginkgo special extract EGb 761 in Alzheimer's disease were compared. The differences in the effects of the active substance and placebo on cognition were measured on the ADAS-Cog scale, taking into account the different degrees of dementia in the various studies and the dropout rate due to adverse drug reactions. Conclusion: Efficacy, expressed as the delay in symptom progression or the difference in response rate between active substance and placebo, showed no major differences between the four cholinesterase inhibitors and the Ginkgo special extract. Only tacrine exhibited a high dropout rate due to adverse drug reactions. In view of this, the subject of new prescriptions should be critically reviewed. Second-generation cholinesterase inhibitors (donepezil, rivastigmine, metrifonate) and Ginkgo special extract EGb 761 should be considered equally effective in the treatment of mild to moderate Alzheimer's dementia. Publication Types: Meta-Analysis
38. Wilt TJ, Ishani A, Rutks I, MacDonald R. Public Health Nutr 2000 Dec;3(4A):459-72. Phytotherapy for benign prostatic hyperplasia. Minneapolis VA Ctr for Chronic Diseases Outcomes Research, MN 55417, USA. [email protected] OBJECTIVE: To systematically review the existing evidence regarding the efficacy and safety of phytotherapeutic compounds used to treat men with symptomatic benign prostatic hyperplasia (BPH). DESIGN: Randomised trials were identified searching MEDLINE (1966: 1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. The studies were included if men had symptomatic benign prostatic hyperplasia, the intervention was a phytotherapeutic preparation alone or combined, a control group received placebo or other pharmacologic therapies for BPH, and the treatment duration was at least 30 days. Key data were extracted independently by two investigators. RESULTS: A total of 44 studies of six phytotherapeutic agents (Serenoa repens, Hypoxis rooperi, Secale cereale, Pygeum africanum, Urtica dioica, Curcubita pepo) met inclusion criteria and were reviewed. Many studies did not report results in a method allowing meta-analysis. Serenoa repens, extracted from the saw palmetto, is the most widely used phytotherapeutic agent for BPH. A total of 18 trials involving 2939 men were reviewed. Compared with men receiving placebo, men taking Serenoa repens reported greater improvement of urinary tract symptoms and flow measures. Serenoa repens decreased nocturia (weighted mean difference (WMD)=-0.76 times per evening; 95% CI=-1.22 to -0.32; n=10 studies) and improved peak urine flow (WMD=1.93 ml s(-1); 95% CI=0.72 to 3.14, n=8 studies). Men treated with Serenoa repens rated greater improvement of their urinary tract symptoms versus men taking placebo (risk ratio of improvement=1.72; 95% CI=1.21 to 2.44, n=8 studies). Improvement in symptoms of BPH was comparable to men receiving the finasteride. Hypoxis rooperi (n=4 studies, 519 men) was also demonstrated to be effective in improving symptom scores and flow measures compared with placebo. For the two studies reporting the International Prostate Symptom Score, the WMD was -4.9 IPSS points (95% CI=-6.3 to -3.5, n=2 studies) and the WMD for peak urine flow was 3.91 ml s(-1) (95% CI=0.91 to 6.90, n=4 studies). Secale cereale (n=4 studies, 444 men) was found to modestly improve overall urological symptoms. Pygeum africanum (n=17 studies, 900 men) may be a useful treatment option for BPH. However, review of the literature has found inadequate reporting of outcomes which currently limit the ability to estimate its safety and efficacy. The studies involving Urtica dioica and Curcubita pepo are limited although these agents may be effective combined with other plant extracts such as Serenoa and Pygeum. Adverse events due to phytotherapies were reported to be generally mild and infrequent. CONCLUSION: Randomised studies of Serenoa repens, alone or in combination with other plant extracts, have provided the strongest evidence for efficacy and tolerability in treatment of BPH in comparison with other phytotherapies. Serenoa repens appears to be a useful option for improving lower urinary tract symptoms and flow measures. Hypoxis rooperi and Secale cereale also appear to improve BPH symptoms although the evidence is less strong for these products. Pygeum africanum has been studied extensively but inadequate reporting of outcomes limits the ability to conclusively recommend it. There is no convincing evidence supporting the use of Urtica dioica or Curcubita pepo alone for treatment of BPH. Overall, phytotherapies are less costly, well tolerated and adverse events are generally mild and infrequent. Future randomised controlled trials using standardised preparations of phytotherapeutic agents with longer study durations are needed to determine their long-term effectiveness in the treatment of BPH. Publication Types: Meta-Analysis
39. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. JAMA 1998 Nov 11;280(18):1604-9. Erratum in: JAMA 1999 Feb 10;281(6):515. Comment in: ACP J Club. 1999 May-Jun;130(3):61. JAMA. 1999 May 12;281(18):1699. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. Dept of Veterans Affairs Coordinating Ctr of the Cochrane Collaborative Review Group in Prostatic Diseases and Urologic Malignancies, Minneapolis Veterans Affairs Medical Ctr, Minn 55417, USA. [email protected] OBJECTIVE: To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH). DATA SOURCES: Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. STUDY SELECTION: Randomised trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days. DATA EXTRACTION: Two investigators for each article (T.J.W., A.I., G.S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies. DATA SYNTHESIS: A total of 18 randomised controlled trials involving 2939 men met inclusion criteria and were analysed. Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n=1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n=10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n=6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n=8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n=2 studies]) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n=2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P<.001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively. CONCLUSION: The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardised preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications. Publication Types: Meta-Analysis
40. Wu AH, Yang D, Pike MC. Cancer Epidemiol Biomarkers Prev 2000 Oct;9(10):1051-8. A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Dept of Preventive Medicine, Univ of Southern California, Los Angeles 90089-9175, USA. [email protected] It has been suggested that consumption of soyfoods may be associated with a reduction in risk of various cancers, including nonhormonally dependent cancers. The purpose of this meta-analysis was to examine the relationship between fermented and unfermented soyfoods and risk of stomach cancer. We searched English language publications of diet and stomach cancer studies that were conducted in Asia or among Asians living in the USA or elsewhere between 1966 and 1999. All of the analytic epidemiological studies that obtained individual data on intake of soyfoods and presented risk estimates of the association between intake of soyfoods and risk of stomach cancer were identified and included in this review. Pooled analysis of 14 studies on fermented soyfoods yielded an odds ratio/relative risk of 1.26 (95% confidence interval, 1.11-1.43) in association with high intake of such foods. In contrast, pooled analysis of 10 studies on unfermented soyfoods found an odds ratio/relative risk of 0.72 (95% confidence interval, 0.63-0.82) in association with high intake of these foods. However, further analyses suggest that fermented and nonfermented soyfoods may be associated with salt and fruit/vegetable intake, respectively; salt and fruit/vegetable intake are directly associated with stomach cancer risk. In almost all of the studies we reviewed, the possible confounding role of salt, fruit/vegetable, and other dietary factors had not been considered in the soyfood analyses. In conclusion, the role of soyfoods in the etiology of stomach cancer cannot be determined with confidence until the roles of potential confounders, including salt, fruit/vegetables, and other dietary factors, are more adequately adjusted for. Publication Types: Meta-Analysis
    

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