Intervention Review

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Artichoke leaf extract for treating hypercholesterolaemia

  1. Barbara Wider1,*,
  2. Max H Pittler2,
  3. Joanna Thompson-Coon3,
  4. Edzard Ernst4

Editorial Group: Cochrane Heart Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 16 AUG 2012

DOI: 10.1002/14651858.CD003335.pub3

How to Cite

Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD003335. DOI: 10.1002/14651858.CD003335.pub3.

Author Information

  1. 1

    University of Exeter Medical School, Institute of Health Services Research, Exeter, UK

  2. 2

    Hospital for Cancer Research, Plau am See, Germany

  3. 3

    University of Exeter, Peninsula CLAHRC, University of Exeter Medical School, Exeter, Exeter, UK

  4. 4

    Peninsula Medical School, Complementary Medicine, Exeter, Devon, UK

*Barbara Wider, Institute of Health Services Research, University of Exeter Medical School, Veysey Building, Salmon Pool Lane, Exeter, EX2 4SG, UK. b.wider@exeter.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 MAR 2013

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of the condition

Hypercholesterolaemia is directly associated with an increased risk of coronary heart disease (CHD) and other sequelae of atherosclerosis (Gould 2007; Laker 2006; NCEP 2002; Verschuren 1995; WHO 2002). Cardiovascular diseases (CVD) are a major cause of death, and 49% of deaths due to CVD are from CHD in particular (Allender 2007). In 2006, CVD cost the UK healthcare system around £14.4 billion and CHD around £3.2 billion (BHF 2009).

The World Health Report estimates that worldwide about 8% of all disease burden in developed countries is caused by raised cholesterol levels in excess of the theoretical minimum, 3.8 mmol/L (WHO 2002). High cholesterol is estimated to cause 18% of global cerebrovascular disease (mostly nonfatal events) and 56% of global ischaemic heart disease amounting to about 4.4 million deaths (7.9% of total) and 40.4 million disability adjusted life years (2.8% of total). According to the guidelines of the National Cholesterol Education Program (NCEP), approximately 30% of Americans have undesirably high serum cholesterol concentrations (NCEP 2002). In England, 70% of men and women had blood cholesterol levels of 5.0 mmol/L and over in 2003 (Allender 2007).

Effective non-pharmacologic treatment consists largely of dietary interventions and increased physical activity, and is considered the treatment of choice for primary and secondary prevention of CHD (Grundy 2004; Poobalan 2004). However, conventional lifestyle management programs are burdened with notoriously poor compliance which often render them impractical. Standard drug therapy includes bile acid sequestrants, nicotinic acid, fibric acids and HMG-CoA reductase inhibitors (statins) (Fintelmann 1996a). None of these pharmacological options is free of adverse events (Law 2006; NCEP 2002; Silva 2006). The potential for carcinogenicity of statins remains unclear (Baigent 2005; Friis 2006). A harmless yet effective treatment option would therefore be of considerable interest.

 

Description of the intervention

Artichoke leaf extract (ALE) has been suggested as such an option. Artichoke (Cynara scolymus) is a herbaceous perennial native to southern Europe, northern Africa and the Canary islands. It contains 1% caffeic acid derivatives, 1% flavonoids, volatile and sesquiterpene (Capasso 2003). For medicinal purposes, extracts of the leaf are used. ALE has traditionally been used as a diuretic and choleretic as well as for jaundice and liver insufficiency.

 

How the intervention might work

In animal studies ALE has been shown to reduce plasma cholesterol and triglycerides (Heidarian 2011; Lietti 1977; Shimoda 2003; Wojcicki 1976; Wojcicki 1978) and to prevent the development of atherosclerotic plaque (Samochowiec 1959; Samochowiec 1962a; Samochowiec 1962b). The anti-atherosclerotic effects are presumed to be linked to the antioxidant effects of ALE, which reduce low-density lipoprotein (LDL) oxidation (Brown 1998) on the one hand, and the inhibition of cholesterol synthesis on the other. In vitro studies on cultured hepatocytes, for instance, suggested that ALE  inhibits the incorporation of 14C-labelled acetate into the non-saponifiable lipid fraction and thus reduces the cholesterol biosynthesis (Gebhardt 1995; Gebhardt 1996a). Other studies suggested indirect inhibitory effects exerted at the level of HMG-CoA reductase (Brown 1998; Fintelmann 1996a; Gebhardt 1996a; Gebhardt 1997; Gebhardt 1998). Luteolin was found to play a major role in the inhibition of cholesterol synthesis (Brown 1998; Gebhardt 1998). Quantitative measurements show that artichoke extract inhibits cholesterol biosynthesis in a concentration-dependent manner (Artner-Dworzak 2000; Gebhardt 1996b). Cholesterol-lowering effects of ALE are also reported in several case reports and uncontrolled studies (Adam 1979; Cima 1959; Dorn 1995; Fintelmann 1996b; Hammerl 1959; Mancini 1960; Siedek 1963; von Weiland 1973; Vorberg 1980; Wegener 1995; Wojcicki 1975; Wojcicki 1981).

 

Why it is important to do this review

Although ALE-containing preparations are today promoted as aids to reduce cholesterol levels and are freely available over the counter or through the Internet, their effectiveness in treating hypercholesterolaemia is unclear, and results from randomized controlled trials (RCTs) need to be evaluated to establish a cause-and-effect relationship.This Cochrane review (Higgins 2011) is an attempt to determine whether ALE is effective for reducing cholesterol levels in patients with hypercholesterolaemia. It is an update of a review first published in 2002 (Pittler 2002) and most recently updated in 2009 (Wider 2009).

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

To assess the efficacy and safety of artichoke leaf extract (ALE) versus placebo or reference medication in the treatment of hypercholesterolaemia, defined as mean total cholesterol levels of at least 5.17 mmol/L (200 mg/dL).

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomised controlled trials (RCTs). We included studies with a parallel group design or cross-over studies if they compared ALE with placebo or reference medication.

There were no restrictions regarding the language of publication (Egger 1997).

 

Types of participants

Participants were patients with hypercholesterolaemia defined as a mean total cholesterol level of at least 5.17 mmol/L (200 mg/dL). There were no age restrictions.

 

Types of interventions

We included trials of oral preparations containing ALE as the only component (mono-preparation). We excluded trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment. There was no specified minimum duration of follow-up.

 

Types of outcome measures

 

Primary outcomes

Changes from baseline in:

  1. Total serum cholesterol levels
  2. Low-density lipopoprotein (LDL) levels
  3. High-density lipoprotein (HDL) levels
  4. Triglyceride levels

 

Secondary outcomes

Adverse events as reported in the included trials.

 

Search methods for identification of studies

 

Electronic searches

We searched the following databases (last updated search 17 May 2012):

  • The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) (2012, Issue 5)
  • MEDLINE Ovid (1966 to May, Week 2, 2012)
  • EMBASE Ovid (1980 to Week 19, 2012)
  • CINAHL Ebsco (1982 to May 2012)
  • AMED (1985 to June 2008, database no longer accessible)
  • CISCOM (1960 to June 2001, database no longer available)

In Appendix 1 we present the search strategies used to search the databases when the review was first published in 2002 and updated in 2009. In Appendix 2 we present the search strategies used in 2012Appendix 1. We used the Cochrane sensitive-maximising RCT filter when searching MEDLINE and EMBASE (Lefebvre 2011).

 

Searching other resources

In addition, we contacted manufacturers of commercial artichoke preparations and experts on the subject and asked them to contribute published and unpublished material. Furthermore, we searched our own files for relevant publications. We searched the bibliographies of the studies retrieved, for further trials.

There were no language restrictions.

 

Data collection and analysis

 

Selection of studies

We extracted data systematically according to methods used, outcome measures, patient characteristics, interventions and results.

 

Data extraction and management

Two authors independently performed the screening of studies, selection, data extraction and the assessment of risk of bias (BW and MHP for this and the 2009 version, MHP and JTC for the 2002 version). We resolved disagreements in the evaluation of individual trials through discussion. The assessment of publication bias and subgroup analyses are not possible due to the scarcity of the available data and will be performed in future reviews.

 

Assessment of risk of bias in included studies

We evaluated the risk of bias according to sequence generation, allocation concealment, blinded assessment of outcomes, loss to follow-up and selective outcome reporting. We extracted data and completed a 'Risk of bias' table for each study. The findings from the 'Risk of bias' assessment are displayed in a 'Risk of bias' summary figure.

 

Measures of treatment effect

We express continuous variables as the mean change from baseline to follow up, and the standard deviation difference from baseline to follow up for each comparison group. We calculated a mean difference (MD) and 95% confidence interval (CI) for each study.

 

Dealing with missing data

We asked the primary authors of studies reporting insufficient data for statistical pooling to provide additional information.

 

Assessment of heterogeneity

Heterogeneity of trials' results was tested with the Chi2 test. We calculated the I2 statistic to give an estimate of the degree of heterogeneity; I2 values over 50% indicate substantial, and over 75% considerable heterogeneity (Higgins 2003). We attempted to explain the differences based on the patient clinical characteristics and interventions of the included studies (Thompson 2001).

 

Assessment of reporting biases

Should more data become available we plan to assess publication bias using a funnel plot based in the data for the primary outcome measure. If there is asymmetry in the funnel plot this will be discussed, as reasons other than publication bias will also need to be considered (Sterne 2001).

 

Data synthesis

Data from each study were pooled as appropriate using a fixed-effect model.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Results of the search

We prepared a QUOROM statement to describe the articles found from the latest update search (Figure 1; Moher 1999). From the results of the original search and the two update searches, we retrieved the full text of 23 articles.

 FigureFigure 1. Study flow diagram.

 

Included studies

Three RCTs assessing oral preparations containing artichoke leaf extract for treating patients with hypercholesterolaemia were included in this review (Bundy 2008; Englisch 2000; Petrowicz 1997); one of them is available as an abstract only (Petrowicz 1997).

Bundy 2008 conducted a randomised, placebo-controlled, parallel-group, single-centre trial in the UK. A total of 75 patients (48 female, 27 male) with total plasma cholesterol levels of 6.0 to 8.0 mmol/L were included. The majority (n = 52) of participants was aged over 50 years and had a mean body mass index (BMI) of over 25 kg/m2. Participants were randomised to receive either 1280 mg ALE or matching placebo daily for 12 weeks. Both groups had similar incidences of prescribed medications, which were mainly used for the prevention or treatment of cardiovascular diseases. Cholesterol-lowering medication was an exclusion criterion for this trial.

Englisch 2000 conducted a randomised, placebo-controlled, double-blind, multicentre trial in Russia. Patients aged between 18 and 70 years with total cholesterol levels of > 7.3 mmol/L (> 280 mg/dL) who had not taken any lipid lowering drugs within two weeks of enrolment were included. Ninety-six women and 47 men were randomised to receive either 1800 mg ALE or placebo daily for 6 weeks. Cholesterol lowering drugs and antibiotic treatment were prohibited during the treatment phase.

The study by Petrowicz (Petrowicz 1997) is available as abstract only and therefore provides limited information. We contacted the author to request additional data (mean differences and SDs) as well as details of methodological issues but no usable data were obtained. In this randomised, placebo-controlled, double-blind pilot study conducted in Germany, forty-four healthy volunteers aged between 20 and 49 years were randomly allocated to receive either 1920 mg artichoke extract daily or indistinguishable placebo for a 12-week treatment period.

 

Excluded studies

We excluded 14 of the 23 full text studies as they were not RCTs, see Characteristics of excluded studies. We identified nine potentially-relevant studies described as randomised trials (Bundy 2008; Dorn 1995; Englisch 2000; Kirchoff 1994; Kupke 1991; Montini 1975; Petrowicz 1997; Rondanelli 2011; Schmiedel 2002). We found no unpublished studies. We excluded six studies for the following reasons: not testing a mono-preparation (Kupke 1991; Rondanelli 2011); not testing whole artichoke leaf extract (Montini 1975); not measuring cholesterol levels (Kirchoff 1994); not controlled although described as randomised (Dorn 1995); ALE as part of a combination treatment package including different dietary interventions and physical therapy (Schmiedel 2002).

 

Risk of bias in included studies

The assessment of risk of bias is presented in the 'Risk of bias table' for each study and in the 'Risk of bias summary figure' (Figure 2). All three trials are described as double-blind and randomised but only in one trial (Bundy 2008) are the randomisation procedure, blinding and allocation concealment fully described (Figure 2). Drop-outs amount to 4 out of 75 patients (5.3%) (Bundy 2008), 12 out of 143 patients (8.4%), (Englisch 2000), while for the study by Petrowicz (Petrowicz 1997) additional data provided by the manufacturer showed none of the 44 participants dropped out. One study is at risk of selective outcome reporting: Petrowicz (Petrowicz 1997) does not report data for the total patient sample but only for a subgroup of patients with higher cholesterol levels at baseline.

 FigureFigure 2. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

 

Effects of interventions

See Additional  Table 1.

In the Bundy 2008 study, the total cholesterol level in participants receiving ALE decreased by 4.2% from 7.16 (0.62) mmol/L at baseline to 6.86 (0.68) mmol/L after 12 weeks, and increased from 6.90 (0.49) mmol/L to 7.04 (0.61) mmol/L in patients receiving placebo; the total difference in change between groups was statistically significant (P = 0.025). No further statistically significant differences between groups were observed for HDL, LDL and triacylglycerol (TAG).

Similarly, no significant differences between groups were reported for well being, food frequency questionnaire, post-study questionnaire and volunteer-rated effectiveness.

Two patients (one in each group) were withdrawn from the study because of adverse events which the authors considered unlikely to be associated with the medication. Both groups reported few and minor adverse events (ALE n = 11, placebo n =16) which also included some positive side effects (ALE n = 6, placebo n = 1).

In the Englisch 2000 trial, total cholesterol levels for patients on ALE decreased by 18.5% or 1.43 mmol/L (from 7.74 mmol/L at baseline to 6.31 mmol/L after 42 ± 3 days of treatment). Total cholesterol levels for patients taking placebo also decreased by 8.6% or 0.66 mmol/L (from 7.69 mmol/L at baseline to 7.03 mmol/L). The difference between the artichoke and placebo groups was statistically significant (P < 0.00001, 95% CI 0.49 to 1.05). LDL levels were also significantly lower for patients receiving ALE, showing a mean decrease of 1.26 mmol/L compared with patients taking placebo where the mean decrease was 0.33 mmol/L (P < 0.00001, 95% CI 0.57 to 1.29). There were no differences between placebo and ALE group for the blood levels of either HDL or triglyceride. Although dietary habits were recorded, the food intake was not strictly controlled in the entire patient sample. In the sample, which included out-patients as well as hospitalised patients, the latter received a standardised and constant hospital diet.

The assessment of global tolerability indicated good to excellent ratings in 68 of 71 patients in the ALE group. The study reported twenty eight adverse events, of which 26 were mild changes in laboratory parameters. These were judged by the authors as 'unlikely' to be related to the artichoke preparation, and were similar in number in both treatment and placebo groups. Data are provided for the liver enzymes gamma-glytamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine transaminase (ALT) and glutamate dehydrogenase (GLDH). There were no relevant changes in these parameters.

In the Petrowicz 1997 study, there were no significant effects on serum cholesterol levels in the total sample. Subgroup analyses were performed in 24 patients with baseline total cholesterol levels of more than 200 mg/dL. The data suggest that patients with an initial total cholesterol level of more than 230 mg/dL experienced a significant reduction in total cholesterol levels compared with patients who received placebo (P = 0.015). Total cholesterol levels at baseline are reported for the two groups together and therefore it was not possible to assess whether baseline data were comparable for both groups. No major adverse events were reported in either group.

Results from two studies were pooled (Bundy 2008; Englisch 2000) while no data suitable for pooling were available from the Petrowicz study (Petrowicz 1997). The mean difference calculated using a fixed-effect model was 0.60 (95% CI 0.40 to 0.79, P < 0.00001) for total cholesterol reduction ( Analysis 1.1) and 0.56 (95% CI 0.34 to 0.78, P < 0.00001) for LDL-cholesterol ( Analysis 1.2) reduction. The mean differences in HDL-cholesterol ( Analysis 1.3) and triglycerides ( Analysis 1.4) reduction were not significant (P = 0.68 and P = 0.92, respectively). Heterogeneity assessed by Chi2test and I2 statistics was present for total cholesterol (I2 = 64%) and LDL cholesterol (I2 = 85%), which persisted when a random-effects model was applied. As values greater than 50% are considered to represent substantial and greater than 75% considerable levels of heterogeneity (Higgins 2003), these results need to be interpreted with caution.

Quality of life was not assessed in two of the studies (Englisch 2000; Petrowicz 1997). Bundy 2008 included a measure of general well-being, the Psychological General Well-Being Index, which showed no significant differences between groups at baseline and after 12 weeks.

The three reviewed trials indicate the absence of serious adverse events in patients treated with 1.2 to 1.9 g of ALE daily. In all studies, adverse events were described as mild and transient. Englisch 2000 reports 28 adverse events; 26 are mild changes in laboratory values, with unlikely relationship to the investigated product and 2 definitely not related to ALE. Petrowicz 1997reports no changes in safety parameters and no major adverse clinical reactions, but provides no further details. Only in the Bundy 2008 study are the adverse events described; most of them occurred in both the ALE and placebo groups with higher incidences in the placebo group. Only constipation was mentioned by 3 in the ALE group versus 0 in the placebo group. Others are flatulence (2 versus 3), headache (0 versus 2), diarrhoea (1 versus 2), tiredness (2 versus 4), dry mouth (2 versus 4), forgetfulness (0 versus 1), and bloating (1 versus 0). Positive side effects concern gastrointestinal tract function (4 versus 1), improved appetite, reduced nausea, and cessation of hot flashes (1 versus 0, respectively).

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Summary of main results

The available evidence from three RCTs including 262 patients suggests a modest positive effect of ALE on total and LDL cholesterol levels, but it is not compelling enough to recommend ALE as a treatment option for hypercholesterolaemia. The results from two studies suggest that patients who have more severely elevated total cholesterol levels at baseline might profit more from ALE than those with moderately elevated levels. These findings need to be further explored before any conclusions for this patient group can be drawn. Adverse events reported in the included trials are generally mild and minor. The changes in laboratory parameters such as liver enzymes reported by Englisch (Englisch 2000) need to be further investigated.

 

Quality of the evidence

All three reviewed trials including a total of 262 patients were of adequate methodological quality, although the study by Petrowicz (Petrowicz 1997) is reported as an abstract only and included a relatively small sample. Treatment outcomes were assessed in a blinded fashion and the loss to follow-up was relatively low. The trials are not flawless, however (Figure 2). The concealment of treatment allocation, for instance, is unclear, and compliance with the treatment regimen seems not to have been formally assessed in two trials (Englisch 2000; Petrowicz 1997). In addition, dietary intake was not rigorously controlled for in the largest trial (Englisch 2000), which would have been important in this sample of predominantly overweight out-patients (mean BMI 28.2). Furthermore, one trial (Petrowicz 1997) reports insufficient data for independent replication, and further contacts did not produce the relevant data. Methodological weaknesses may detract from the validity of trial results and distort the findings (Moher 1998).

The reduction of cholesterol reported in the most rigorous trial by Bundy et al (Bundy 2008) is smaller (6.1% over placebo) than that observed in the study by Englisch et al (9.9%) (Englisch 2000). Statistical testing for heterogeneity revealed substantial heterogeneity for total cholesterol (I2 = 64%) and considerable heterogeneity for LDL cholesterol (I2 = 85%).

The differences could be attributed to several factors. The quantity and type of ALE used differed between the studies. While Englisch et al (Englisch 2000) used 1800 mg of a narrow-spectrum aqueous extract, Bundy et al (Bundy 2008) used 1280 mg of broad-spectrum aqueous extract which is likely to contain lower amounts of certain active phytochemicals such as, for example, luteolin.

The mean baseline total cholesterol values in Bundy 2008 were lower than in Englisch 2000 (7.16 mmol/L in the ALE group and 6.90 mmol/L in the placebo group, versus 7.74 mmol/L in the ALE and 7.69 mmol/L in the placebo group, respectively). Similarly, in (Petrowicz 1997, significant differences were only detected in a subgroup with higher baseline cholesterol levels of 5.9 mmol/L compared to 5.2 mmol/L of the total sample.

Overall the participants in the Bundy study (Bundy 2008) seem to have been more health conscious than average, reporting ‘healthy’ dietary habits in their food diary and higher herbal and other dietary supplement use. No details of dietary intake are reported in the studies by Englisch et al (Englisch 2000) and Petrowicz (Petrowicz 1997) so no comparisons can be made.

 

Agreements and disagreements with other studies or reviews

These results update and extend the findings of a previous systematic review (Pittler 1998) and a Cochrane review (Pittler 2002; Wider 2009). More rigorous randomised clinical trials, assessing larger patient samples over longer treatment periods, and including subgroups of patients with highly rather than moderately elevated cholesterol levels are required. Careful study of relevant cardiovascular outcome measures and safety aspects are also needed (Ernst 2006).

The size of the effect reported in the reviewed trials is similar to the relative cholesterol reduction attributable to garlic (Allium sativa) which ranges between 5.8% (Stevinson 2000) and 9.9% (Alder 2003). The percentage reduction of total cholesterol attributable to dietary advice ranges from 6% for the Mediterranean diet to 10% for a low fat diet according to the National Cholesterol Education Program (NCEP) Step 1 diet  (Buckley 2007). Compared with conventional pharmaceutical options for lowering cholesterol, however, the effect of ALE is unimpressive. For statin drugs, for instance, systematic reviews of randomised clinical trials have reported reductions in total cholesterol from baseline of between 22% and 34% (Herbert 1997; Ross 1999; Gould 2007) compared with 0.6% for placebo (Ross 1999).

The traditional use of a plant-based remedy implies relative safety but provides no proof whether such remedies are without adverse events (Ernst 1998). A MEDLINE search via PubMed from its inception to December 2008 retrieved 9 clinical trials of artichoke for any condition (Fintelmann 1996b; Fintelmann 1997; Fintelmann 1999; Held 1992; Holtmann 2003; Lupattelli 2004; Marakis 2002; Pittler 2003; Walker 2001) reporting adverse events. These studies mainly found mild and transient adverse events relating to the gastro-intestinal system, suggesting that ALE is relatively well tolerated.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

Some data from clinical trials assessing artichoke leaf extract (ALE) for treating hypercholesterolaemia exist. The available evidence is not compelling enough to recommend ALE as a treatment option for hypercholesterolaemia. The limited data on safety suggest mild, transient and infrequent adverse events with the short term use of ALE.

 
Implications for research

The lipid-lowering effects of artichoke leaf extract (ALE) are supported by in vitro and animal experiments. Better clinical trials assessing larger patient samples over longer intervention periods, particularly in patients with highly rather than moderately elevated cholesterol levels, are needed to establish whether ALE is an effective and safe treatment option for patients with hypercholesterolaemia.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. Artichoke leaf extract vs placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Total cholesterol reduction (mmol/L)2211Mean Difference (IV, Fixed, 95% CI)0.60 [0.40, 0.79]

 2 LDL-cholesterol reduction (mmol/L)2211Mean Difference (IV, Fixed, 95% CI)0.56 [0.34, 0.78]

 3 HDL-cholesterol reduction (mmol/L)2211Mean Difference (IV, Fixed, 95% CI)0.03 [-0.11, 0.17]

 4 Triglycerides reduction (mmol/L)2211Mean Difference (IV, Fixed, 95% CI)-0.01 [-0.25, 0.22]

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Search strategies used in 2001 and 2008

 

CENTRAL

#1 artichok* in All Text
#2 cynara* in All Text
#3 cynarin* in All Text
#4 artischocke* in All Text
#5 hepar in All Text
#6 valverde in Abstract
#7 hewechol in All Text
#8 hepagallin in All Text
#9 cy450 in All Text
#10 cynatol in All Text
#11 artishok* in All Text
#12 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11)

 

MEDLINE (on Ovid)

1 Cynara Scolymus/
2 (artichoke$ or artischocke$).tw.
3 cynara scolymus.tw.
4 cynarin.tw.
5 hepar sl.tw.
6 valverde.tw.
7 hewechol.tw.
8 hepagallin.tw.
9 cy450.tw.
10 cynatol.tw.
11 artishok$.tw.
12 or/1-11
13 exp Cholesterol/
14 exp Hyperlipidemia/
15 exp Antilipemic Agent/
16 cholesterol$.tw.
17 lipid$.tw.
18 hyperlipid$.tw.
19 antilip$.tw.
20 or/13-19
21 12 and 20
22 ae.fs.
23 adverse.tw.
24 side effect$.tw.
25 exp Hypersensitivity/
26 allerg$.tw.
27 exp Product Surveillance, Postmarketing/
28 or/22-27
29 12 and 28
30 29 or 21
31 exp animals/ not humans/
32 30 not 31

 

EMBASE (on Ovid)

1 exp artichoke/
2 Cynara Scolymus Extract/
3 Cynara Scolymus/
4 (artichoke$ or artischocke$).tw.
5 cynara scolymus.tw.
6 cynarin.tw.
7 hepar sl.tw.
8 valverde.tw.
9 hewechol.tw.
10 hepagallin.tw.
11 cy450.tw.
12 cynatol.tw.
13 artishok$.tw.
14 or/1-13
15 exp Cholesterol/
16 exp Hyperlipidemia/
17 exp Antilipemic Agent/
18 cholesterol$.tw.
19 lipid$.tw.
20 hyperlipid$.tw.
21 antilip$.tw.
22 or/15-21
23 ae.fs.
24 adverse.tw.
25 side effect$.tw.
26 exp Hypersensitivity/
27 allerg$.tw.
28 exp Side Effect/
29 exp Adverse Drug Reaction/
30 or/23-29
31 14 and 22
32 14 and 30
33 31 or 32
34 (exp animal/ or exp nonhuman/) not exp human/
35 33 not 34

 

AMED (Allied and Complementary Medicine, on Ovid)

1 cynara scolymus/
2 (artichoke$ or artischocke$).tw.
3 cynara scolymus.tw.
4 cynarin.tw.
5 hepar sl.tw.
6 valverde.tw.
7 hewechol.tw.
8 hepagallin.tw.
9 cy450.tw.
10 cynatol.tw.
11 artishok$.tw.
12 or/1-11

 

CINAHL (On EBSCO)

(artichok* or artischock* or cynara scolymus or "hepar sl" or valverde or hewechol or hepagallin or cy450 or cynatol or artishok*)

 

Search terms described in original version of the review (2001)

The search terms used were artichoke, Cynara scolymus, cynarin, Artischocke (the German common name for Cynara scolymus) and included trade names: Hepar SL, Valverde, Hewechol, Hepagallin, CY450 and Cynatol.

 

Appendix 2. Search strategies used for 2012 update

 

CENTRAL

#1           MeSH descriptor Cynara scolymus, this term only

#2           (artichoke* or artischocke*)

#3           (cynara scolymus)

#4           (cynarin)

#5           (hepar sl)

#6           (valverde)

#7           (hewechol)

#8           (hepagallin)

#9           (cy450)

#10         (cynatol)

#11         (artishok*)

#12         (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11)

#13         (#12), from 2008 to 2012

 

 

 

MEDLINE Ovid

1     Cynara Scolymus/

2     (artichoke$ or artischocke$).tw.

3     cynara scolymus.tw.

4     cynarin.tw.

5     hepar sl.tw.

6     valverde.tw.

7     hewechol.tw.

8     hepagallin.tw.

9     cy450.tw.

10     cynatol.tw.

11     artishok$.tw.

12     or/1-11

13     exp Cholesterol/

14     exp Hyperlipidemia/

15     exp Antilipemic Agent/

16     cholesterol$.tw.

17     lipid$.tw.

18     hyperlipid$.tw.

19     antilip$.tw.

20     or/13-19

21     12 and 20

22     ae.fs.

23     adverse.tw.

24     side effect$.tw.

25     exp Hypersensitivity/

26     allerg$.tw.

27     exp Product Surveillance, Postmarketing/

28     or/22-27

29     12 and 28

30     29 or 21

31     exp animals/ not humans/

32     30 not 31

33     limit 32 to yr="2008 -Current"

 

 

EMBASE Ovid

1     Cynara Scolymus/

2     (artichoke$ or artischocke$).tw.

3     cynara scolymus.tw.

4     cynarin.tw.

5     hepar sl.tw.

6     valverde.tw.

7     hewechol.tw.

8     hepagallin.tw.

9     cy450.tw.

10     cynatol.tw.

11     artishok$.tw.

12     or/1-11

13     exp Cholesterol/

14     exp Hyperlipidemia/

15     exp Antilipemic Agent/

16     cholesterol$.tw.

17     lipid$.tw.

18     hyperlipid$.tw.

19     antilip$.tw.

20     or/13-19

21     12 and 20

22     ae.fs.

23     adverse.tw.

24     side effect$.tw.

25     exp Hypersensitivity/

26     allerg$.tw.

27     exp Product Surveillance, Postmarketing/

28     or/22-27

29     12 and 28

30     29 or 21

31     exp animals/ not humans/

32     30 not 31

33     limit 32 to yr="2008 -Current"

 

 

CINAHL Plus (EBSCO)

S13  S12  Limiters - Published Date from: 20080601-20120531

S12  S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 

S11  artishok* 

S10  cynatol 

S9  cy450 

S8  hepagallin 

S7  hewechol 

S6  valverde 

S5  hepar sl 

S4  cynarin 

S3  cynara scolymus 

S2  artichoke* or artischocke* 

S1  (MH "Artichoke") 

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 16 August 2012.


DateEventDescription

19 December 2012New citation required but conclusions have not changedWith no new studies included the conclusions remain the same.

11 July 2012New search has been performedSearch updated to 17 May 2012. No new clinical trials identified. Conclusions have not changed.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Protocol first published: Issue 3, 2001
Review first published: Issue 3, 2002


DateEventDescription

16 December 2008New search has been performedSearch updated to 25 June 2008. 1 new study identified and included. Conclusion has not changed significantly.

16 December 2008New citation required but conclusions have not changedNew authors added.

8 September 2008AmendedConverted to new review format.

8 April 2002New citation required and conclusions have changedSubstantive amendment



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Conception and design: MH Pittler, E Ernst
Literature searches: B Wider, MH Pittler, J Thompson Coon
Analysis and interpretation of the data: B Wider, MH Pittler, J Thompson Coon, E Ernst
Drafting of the review: MH Pittler, E Ernst
Critical revision of the review for important intellectual content: B Wider, MH Pittler, J Thompson Coon, E Ernst
Final approval of the review: B Wider, MH Pittler, J Thompson Coon, E Ernst

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, UK.
    Salaries for authors who all are or were employees of the Peninsula Medical School (now University of Exeter Medical School).

 

External sources

  • No sources of support supplied

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Bundy 2008 {published data only}
  • Bundy R, Walker AF, Middleton RW, Wallis C, Simpson HC. Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial. Phytomedicine 2008;15:668-75.
Englisch 2000 {published data only}
  • Englisch W, Beckers C, Unkauf M, Ruepp M, Zinserling V. Efficacy of artichoke dry extract in patients with hyperlipoproteinemia. Arzneimittel-Forschung 2000;50:260-5.
Petrowicz 1997 {published data only}
  • Petrowicz O, Gebhardt R, Donner M, Schwandt M, Kraft K. Effects of artichoke leaf extract (ALE) on lipoprotein metabolism in vitro and in vivo. Atherosclerosis 1997;129:147.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Anon 2007 {published data only}
  • High-dose extract from the leaves of artichoke increases choleresis and lowers the cholesterol level [Hochdosierter artischockenblatterextrakt steigert cholerese und senkt cholesterinspiegel]. Schweizerische Zeitschrift fur GanzheitsMedizin 2007;19:295-8.
Anon 2008 {published data only}
  • Artichoke leaf extract in the treatment of hyperlipoproteinemia [Artischockenblatterextrakt bei hyperlipoproteinamie]. Schweizerische Zeitschrift fuer GanzheitsMedizin 2008;20:73-4.
Dog 2003 {published data only}
Dorn 1995 {published data only}
  • Dorn M. Improvement in raised lipid levels with artichoke juice (Cynara scolymus L). British Journal of Phytotherapy 1995/1996;4:21-6.
Goetz 2007 {published data only}
  • Goetz P, Le Jeune R. Artichoke, Cynara scolymus. Phytotherapie 2007;5:219-22.
Hausler 2003 {published data only}
  • Hausler M, Ganzera M, Stuppner H, Abel G, Popp M. Artichoke preparations [Artischocken-praparate]. Deutsche Apotheker Zeitung 2003;143:64-73.
Joy 2007 {published data only}
Kirchoff 1994 {published data only}
  • Kirchhoff R, Beckers CH, Kirchhoff GM, Trinczek-Gaertner H, Petrowicz O, Reimann H-J. Increase in choleresis by means of artichoke extract. Phytomedicine 1994;1:107-15.
Kraft 2002 {published data only}
  • Kraft K. Artichoke leaf extract and pectin may lower serum cholesterol. Focus on Alternative and Complementary Therapies 2002;7:350-1.
Kupke 1991 {published data only}
  • Kupke D, Sanden von H, Trinczek-Gaertner, Lewin J, Bluemel, Reimann H-J. An evaluation of the choleretic activity of a plant-based cholagogue [Pruefung der choleretischen Aktivitaet eines pfanzlichen Cholagogums]. Zeitschrift fur Allgemeinmedizin 1991;67:1046-58.
Lupattelli 2004 {published data only}
Meletis 2003 {published data only}
  • Meletis CD. Cardiovascular disease: phytochemical and nutritional prevention and treatment. Alternative and Complementary Therapies 2003;9:158-62.
Montini 1975 {published data only}
  • Montini M, Levoni P, Ongaro A, Pagani G. Controlled application of cynarin in the treatment of hyperlipemic syndrome. Observations in 60 cases [Kontrollierte Anwendung von Cynarin in der Behandlung hyperlipaemischer Syndrome]. Arzneimittel-Forschung 1975;25:1311-4.
Nazni 2006 {published data only}
  • Nazni P, Poongodi VT, Alagianambi P, Amirthaveni M. Hypoglycemic and hypolipidemic effect of Cynara scolymus among selected type 2 diabetic individuals. Pakistan Journal of Nutrition 2006;5:147-51.
Pittler 2001 {published data only}
  • Pittler MH. Encouraging findings for artichoke extract in the treatment of hyperlipoproteinaemia. Focus on Alternative and Complementary Therapies 2001;6:13-4.
Rondanelli 2011 {published data only}
  • Rondanelli M, Giacosa A, Orsini F, Opizzi A, Villani S. Appetite control and glycaemia reduction in overweight subjects treated with a combination of two highly standardized extracts from phaseolus vulgaris and Cynara scolymus. Phytotherapy Research 2011;25:1275-82.
Schmiedel 2002 {published data only}
  • Schmiedel V. Cholesterol-lowering effects of artichoke and dietary fibre [Senkung des Cholesterinspiegels durch Artischocke und Ballaststoffe]. Erfahrungsheilkunde 2002;51:405-14.
Springer 2003 {published data only}
  • Springer D. High-dose artichoke improves choleresis and lowers blood lipids [Hochdosierter Artischockenextrakt steigert Cholerese und senkt die Blutfette]. Gesundes Leben 2003;80:22-5.
Thompson 2003 {published data only}
  • Thompson Coon JS, Ernst E. Herbs for serum cholesterol reduction: a systematic view. Journal of Family Practice 2003;52:468-72.
Wolf 1996 {published data only}
  • Wolf E. Artichoke for lowering cholesterol level. Pharmazeutische Zeitung 1996;141:35-6.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
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Ernst 1998
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Gebhardt 1995
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References to other published versions of this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Pittler 1998
Pittler 2002
  • Pittler MH, Thompson Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database of Systematic Reviews 2002, Issue 3. [DOI: 10.1002/14651858.CD003335]
Wider 2009