Artichoke leaf extract for treating hypercholesterolaemia

  • Review
  • Intervention

Authors


Abstract

Background

Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE) has been implicated in lowering cholesterol levels. Whether ALE is truly effective for this indication is still a matter of debate. This is an update of a review first published in 2002 and last updated in 2009.

Objectives

To assess the efficacy and safety of ALE in the treatment of hypercholesterolaemia.,

Search methods

We updated searches of 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 2012 Week 19); and CINAHL Ebsco (1982 to May 2012) on 17 May 2012. CISCOM was last searched until June 2001, and AMED until June 2008. We checked reference lists of articles, and contacted manufacturers of preparations containing artichoke extract, and experts on the subject. No language restrictions were applied.

Selection criteria

We included randomised controlled trials (RCTs) of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia. We excluded trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment.

Data collection and analysis

Data were extracted systematically and risk of bias was evaluated using the Cochrane 'Risk of bias' tool. Two authors independently performed the screening of studies, selection, data extraction and assessment of risk of bias. Disagreements in the evaluation of individual trials were resolved through discussion.

Main results

We included three RCTs involving 262 participants. The trials were of adequate methodological quality but had some shortcomings. One trial was at low quality of risk, one at medium and one of unclear risk of bias. One trial is available as abstract only and includes a small sample. In the first trial the total cholesterol level in participants receiving ALE decreased by 4.2% from 7.16 (0.62) mmol/L 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 being statistically significant (P = 0.025). In the second trial ALE reduced total cholesterol levels by 18.5% from 7.74 mmol/L to 6.31 mmol/L after 42 ± 3 days of treatment, whereas placebo reduced cholesterol by 8.6% from 7.69 mmol/L to 7.03 mmol/L (P = 0.00001). The third trial, which is available as abstract only and provides limited data, stated that ALE significantly reduced blood cholesterol compared with placebo in a subgroup of patients with baseline total cholesterol levels of more than 230 mg/dL (P < 0.05). Trial reports indicate mild, transient and infrequent adverse events.

Authors' conclusions

Data from three clinical trials assessing ALE for treating hypercholesterolaemia are available. Athough the trials are of adequate methodological quality they have some shortcomings and one is available as abstract only. There is an indication that ALE has potential in lowering cholesterol levels, but the evidence is, as yet, not convincing. The limited data on safety suggest only mild, transient and infrequent adverse events with the short term use of ALE.

Résumé scientifique

Extrait de feuilles d'artichaut pour le traitement de l'hypercholestérolémie

Contexte

L'hypercholestérolémie est directement associée à un risque accru de maladie coronarienne et à d'autres séquelles de l'athérosclérose. L'extrait de feuilles d'artichaut (EFA) est utilisé pour abaisser le taux de cholestérol. L'efficacité véritable de l'EFA dans ce contexte reste sujette à débat. Ceci est une mise à jour d'une revue publiée pour la première fois en 2002 et précédemment mise à jour en 2009.

Objectifs

Évaluer l'efficacité et l'innocuité de l'EFA dans le traitement de, l'hypercholestérolémie.

Stratégie de recherche documentaire

Nous avons mis à jour les recherches dans le registre Cochrane des essais contrôlés (CENTRAL, La Bibliothèque Cochrane ) (2012, numéro 5) ; MEDLINE Ovid (de 1966 à la 2ème semaine de mai 2012) ; EMBASE Ovid (de 1980 à la 19ème semaine de l'année 2012) ; et CINAHL (Ebsco 1982 à mai 2012) le 17 mai 2012. les dernières recherches dans CISCOM ont été effectuées jusqu'en juin 2001, et dans AMED jusqu' en juin 2008. Nous avons examiné les références bibliographiques des articles et contacté des fabricants de préparations contenant de l'extrait d'artichaut, et des experts en la matière. Aucune restriction de langue n'a été appliquée.

Critères de sélection

Nous avons inclus des essais contrôlés randomisés (ECR) comparant des monopréparations à base d'EFA par rapport à un placebo ou un médicament de référence pour les patients présentant une hypercholestérolémie. Nous avons exclu les essais évaluant l'EFA comme l'un des principes actifs dans une préparation combinée ou dans le cadre d'un traitement combiné.

Recueil et analyse des données

Les données ont été extraites de manière systématiques et le risque de biais a été évalué à l'aide de l'outil Cochrane « Risque de biais ». Deux auteurs ont indépendamment effectué l'identification et la sélection des études, l'extraction des données et l'évaluation du risque de biais. les désaccords dans l'évaluation des essais individuels ont été résolus par discussion.

Résultats principaux

Nous avons inclus trois ECR impliquant 262 participants. Les essais étaient de qualité méthodologique adéquate mais présentaient des lacunes. Un essai était à faible qualité de risque, un essai à moyen et un à risque incertain de biais. Un essai est disponible sous forme de résumé uniquement et inclut un échantillon de petite taille. Dans le premier essai, la cholestérolémie totale chez les participants recevant de l'EFA diminuait de 4,2 % de 7,16 (0,62) mmol/l à 6,86 (0,68) mmol/l au bout de 12 semaines, et augmentait de 6,90 (0,49) mmol/l à 7,04 (0,61) mmol/l chez les patients recevant un placebo, la différence totale est statistiquement significative (P =0,025). Dans le deuxième essai, l'EFA réduisait la cholestérolémie totale de 18,5 % de 7,74 mmol/l à 6,31 mmol/l au bout de 42 ± 3 jours de traitement, tandis que le placebo réduisait le cholestérol de 8,6%, de 7,69 mmol/l à 7,03 mmol/l (P =0,00001). Le troisième essai, qui est disponible sous forme de résumé uniquement et fournit des données limitées, indiquaient que l'EFA réduisait significativement le taux de cholestérol dans le sang par rapport à un placebo dans un sous-groupe de patients atteints au départ d'une cholestérolémie totale supérieure à 230 mg/dl (P < 0,05). Les rapports des essais signalaient des légers, passagers et peu fréquents événements indésirables.

Conclusions des auteurs

Les données issues de trois essais cliniques comparatifs évaluant l'EFA pour le traitement de l'hypercholestérolémie sont disponibles. bien que les essais soient de qualité méthodologique adéquate ils ont des lacunes et un est disponible sous forme de résumé uniquement. Il y a quelques indices que l'EFA pourrait permettre de réduire le taux de cholestérol, mais les preuves ne sont pas encore, convaincantes. Les données limitées sur l'innocuité suggèrent que les événements indésirables sont seulement légers, passagers et peu fréquents avec l'utilisation à court terme de l'EFA.

アブストラクト

高コレステロール血症治療のためのアーティチョーク葉エキス

背景

高コレステロール血症は、冠動脈心疾患、その他のアテローム性動脈硬化による続発症に対するリスク上昇と直接的な関連がある。アーティチョーク葉エキス(ALE)はコレステロール値の低下に関与しているといわれている。しかし、ALEが本当にこの適応症に有効であるか否かについては、未だに議論の的である。本レビューは2002年に初版を発表、2009年に更新されたレビューの再更新である。

目的

高コレステロール血症の治療のためのALEの有効性と安全性を評価すること。

検索戦略

Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library)(2012年第5版)、MEDLINE Ovid (1966年~2012年5月第2週)、 EMBASE Ovid (1980年~2012年第19週)、およびCINAHL Ebsco(1982年~2012年5月)を2012年5月17日に検索した。 CISCOMは2001年6月までを、AMEDは2008年6月までを検索した。関連資料について論文の文献リストも検索し、アーティチョーク・エキスを含有する製剤の製造業者およびこの主題の専門家にも問い合わせた。言語の制限は設けなかった。

選択基準

高コレステロール血症患者に対してALE単剤製剤とプラセボまたは関連作用薬を比較しているランダム化比較試験(RCT)を含めた。ALEを配合剤に含まれるいくつかの活性成分のひとつとして、または併用療法の一部として評価している試験は除外した。

データ収集と分析

データをシステマティックに抽出し、Cochraneのツール「バイアスのリスク」を使用してバイアスのリスクを評価した。2名の著者が独立して研究をスクリーニングし、選択し、データを抽出し、バイアスのリスクを評価した。個別の試験評価の相違点は議論を通じて解決した。

主な結果

参加者262名を対象としたRCT試験3件を選択した。試験の方法論的質は十分であったが、不十分な点もあった。1件の試験ではリスクの質が低く、1件は中等度であり、もう1件はバイアスのリスクが不明瞭であった。1件は抄録のみが閲覧可能であり、サンプル・サイズが小さかった。1件目の試験では、ALE投与の参加者の総コレステロール値が投与開始12週間後に7.16(0.62)mmol/L から 6.86(0.68)mmol/Lに4.2%低下した一方、プラセボの参加者は6.90(0.49)mmol/Lから 7.04(0.61)mmol/Lに上昇した。全差は統計学的に有意であった(P = 0.025)。2件目の試験では、ALEで投与開始42±3日後に総コレステロール値が7.74 mmol/L から6.31 mmol/Lに18.5%低下し、プラセボでは7.69 mmol/L から7.03 mmol/Lに8.6%低下した(P = 0.00001)。3件目の試験は抄録のみが閲覧可能であり、データが限られていたが、ベースラインの総コレステロール値が230 mg/ dLを超えるサブグループ患者において、プラセボと比較して血中コレステロールがALEで有意に減少した(P < 0.05)ことが示されていた。軽度で一過性の稀な有害事象が、試験で報告されている。

著者の結論

高コレステロール血症の治療においてALEを評価する臨床試験3件のデータが入手可能である。試験の方法論的質は十分であるが、不十分な点もあり、1件は抄録のみが閲覧可能である。ALEはコレステロール値を低下させる可能性があることが示されているが、エビデンスはまだ説得力がない。安全性に関する限定的なデータによって、ALEの短期投与による軽度で一過性の稀な有害事象が示唆されている。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2015.12.29]《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Artichoke leaf extract for treating high cholesterol levels

Too much cholesterol in the blood can lead to cholesterol depositing on the walls of the arteries (major blood vessels). This blocks the arteries and can cause heart attacks and strokes. High cholesterol can be lowered by quitting smoking, dietary changes and exercise. Some drugs such as statins are also used, but these can have adverse events.

Artichoke (Cynara scolymus) leaf extract is a herbal remedy marketed as an aid to lowering cholesterol. We undertook a systematic search for clinical trials of artichoke leaf extract used to reduce high cholesterol levels. We included trials if they used artichoke leaf extract on its own (not as part of a combination product) and compared it to placebo or another medication.

We found only three clinical trials including a total of 262 participants that met the inclusion criteria. One study was at low risk of bias while for the other two the risk was either medium or unclear. One trial was only reported as a short abstract and did not provide full data.

Overall the trials found that artichoke leaf extract had a modest positive effect on cholesterol levels. However, the results are not compelling enough to recommend artichoke leaf extract as a treatment option for high cholesterol levels. Adverse events were only mild and transient. The review concluded that more research is needed before any firm conclusions can be drawn.

Résumé simplifié

Extrait de feuilles d'artichaut pour le traitement du taux de cholestérol élevé

trop de cholestérol dans le sang peut entraîner des dépôts sur les parois des artères (principaux vaisseaux sanguins). Cela obstrue les artères et peut entraîner des crises cardiaques et des AVC. un cholestérol élevé peut être réduit par le sevrage tabagique, les changements alimentaires et l'exercice. Certains médicaments tels que les statines sont également utilisés, mais ils peuvent être associés à des événements indésirables.

L'extrait de feuilles d'artichaut ( Cynara scolymus ) est un remède à base de plantes commercialisé pour aider à réduire le cholestérol. Nous avons entrepris une recherche systématique d'essais cliniques de l'extrait de feuilles d'artichaut utilisé pour réduire les niveaux de cholestérol élevé. Nous avons inclus des essais s'ils avaient utilisé l'extrait de feuilles d'artichaut seul (pas dans le cadre d'une combinaison produit), en comparaison à un placebo ou un autre médicament.

Nous n'avons trouvé que trois essais cliniques portant sur un total de 262 participants qui répondaient aux critères d'inclusion. Une étude était à faible risque de biais, tandis que pour les deux autres le risque était soit moyen ou incertain. Un essai n'a été rapporté que sous forme de court résumé et n'a pas fourni de données complètes.

Globalement, les essais ont déterminé que l'extrait de feuilles d'artichaut avaient un effet positif modeste sur le taux de cholestérol. Cependant, les résultats ne sont pas suffisamment solides pour recommander l'extrait de feuilles d'artichaut comme une option de traitement pour des taux de cholestérol élevés. Les événements indésirables n'ont été que légers et passagers. La revue a conclu que des recherches supplémentaires sont nécessaires avant de pouvoir tirer des conclusions définitives.

Notes de traduction

Traduit par: French Cochrane Centre 5th November, 2013
Traduction financée par: Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux

Laički sažetak

Ekstrakt lišća artičoke za liječenje visokih razina kolesterola

Previše kolesterola u krvi može uzrokovati taloženje kolesterola na stijenkama arterija (glavnih krvnih žila). To začepljuje arterije te može uzrokovati srčani i moždani udar. Prestanak pušenja, promjene u prehrani te vježbanje mogu smanjiti visoke razine kolesterola. Neki lijekovi, na primjer statini, se također koriste, ali oni mogu imati nuspojave.

Ekstrakt lišća artičoke (lat. Cynara scolymus) je biljni lijek koji se reklamira kao pomoć pri snižavanju kolesterola. Proveden je Cochrane sustavni pregled kako bi se pronašla klinička istraživanja koja su ispitivala korištenje ekstrakta lišća artičoke za snižavanje visokih razina kolesterola. Uključena su ispitivanja koja su koristila isključivo ekstrakt lišća artičoke (ne u kombinaciji s drugim proizvodima) i usporedila ga s placebom ili drugim lijekom.

Pronađena su samo tri klinička istraživanja koja su zadovoljila kriterije za uključivanje, s ukupno 262 sudionika. Jedna je studija imala nizak rizik od pristranosti, a druge dvije su imale ili srednji ili nedovoljno jasan rizik od pristranosti. Jedno ispitivanje objavljeno je samo kao kongresni sažetak te nije navelo potpune podatke.

Sveukupno su istraživanja otkrila kako je ekstrakt lišća artičoke imao umjereno pozitivne učinke na razinu kolesterola. Međutim, rezultati nisu dovoljno uvjerljivi da bismo preporučili ekstrakt lišća artičoke kao mogući način liječenja visoke razine kolesterola. Negativni su učinci bili blagi i prolazni. U ovom je sustavnom pregledu zaključeno kako su potrebna dodatna istraživanja prije donošenja čvrstih zaključaka.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Marija Lučić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

平易な要約

高コレステロール血症治療のためのアーティチョーク葉エキス

血中にコレステロールがあまりにも多いと、動脈(大血管)の壁にコレステロールが沈着する。沈着したコレステロールは動脈を塞ぎ、心臓発作や脳卒中を引き起こす場合がある。高コレステロールは、禁煙や食事の変更および運動で下げることができる。スタチンなどの薬物も使われるが、有害事象を起こす場合がある。

アーティチョーク(Cynara scolymus)の葉のエキスは、コレステロール値を下げるのに効果があるとして市販されているハーブ剤である。 高コレステロール値を下げるためにアーティチョーク葉エキスを使った臨床試験をシステマティックに検索した。アーティチョーク葉エキスのみを使用し(配合剤の成分のひとつではなく)、プラセボまたは他の薬剤と比較した試験を選択した。

参加総数262名の3件の臨床試験のみが選択基準に適合した。1件はバイアスのリスクが低く、他の2件のリスクは中程度または不明瞭であった。1件の試験は短い抄録だけの報告であり、全データはなかった。

全体として、試験からはアーティチョーク葉エキスにはコレステロール値に対して軽微の効果があることがわかった。しかしその結果は、高コレステロールの治療の選択肢としてアーティチョーク葉エキスを推奨するほど説得力はない。有害事象は軽度で一過性のものだけであった。このレビューでは、確かな結論を導き出すまでにさらなる研究が必要であると結論づけている。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2015.12.29]《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Background

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

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

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

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.

Figure 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.

Figure 2.

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

Effects of interventions

See Additional Table 1.

Table 1. Results
StudyResults
Bundy 2008Mean changes in total cholesterol concentration - 4.2% for the active group and + 1.9% for the placebo group, total difference (6.1%). Statistically significant (P = 0.025).
No further statistically significant differences in HDL, LDL, TAG between groups.
Only few and minor adverse events which occurred more frequently in the placebo group (11 vs 16). Positive side effects occurred more frequently in ALE group (n = 7) than placebo group (n = 1).
Englisch 2000

Mean reduction of total cholesterol was 18.5% (1.43 mmol/L) for the treatment group and 8.6% for the placebo group (0.66 mmol/L), difference of means 9.9%. Statistically significant.

LDL-cholesterol decreased by 22.9% in the ALE group and 6.3% in the placebo group. Difference 16.6%. Statistically significant.

LDL/HDL ratio decreased by 20.2% in ALE group and 7.2% in placebo group. Difference between group 13%.

No statistically significant differences between groups for HDL cholesterol and triglycerides.

26 mild changes in laboratory values including liver enzymes, authors state that the "relationship to the investigational product is rated 'unlikely' in all cases", 2 major AEs unrelated to drug (coronary bypass surgery, pacemaker implantation).

Petrowicz 1997No effect on total cholesterol reduction in total patient population. Sub-group analysis in patients with initial total cholesterol levels of above 210 mg/dL showed that ALE significantly reduced total cholesterol compared with placebo. But this was on few patients therefore data are of limited power, n = 7 control/placebo arm and n = 10 in the treatment arm.

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

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

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

None.

Data and analyses

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]
Analysis 1.1.

Comparison 1 Artichoke leaf extract vs placebo, Outcome 1 Total cholesterol reduction (mmol/L).

Analysis 1.2.

Comparison 1 Artichoke leaf extract vs placebo, Outcome 2 LDL-cholesterol reduction (mmol/L).

Analysis 1.3.

Comparison 1 Artichoke leaf extract vs placebo, Outcome 3 HDL-cholesterol reduction (mmol/L).

Analysis 1.4.

Comparison 1 Artichoke leaf extract vs placebo, Outcome 4 Triglycerides reduction (mmol/L).

Appendices

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

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

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

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

None known.

Sources of support

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

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Bundy 2008

MethodsRandomised, double-blind
2 parallel arms
Participants75 patients with total plasma cholesterol of 0.6 - 0.8 mmol/L
majority of patients (n = 52) over 50 years of age
48 female (24 in each group), 27 male (ALE 14, placebo 13)
Treatment arm: n = 38
Placebo arm n = 37
InterventionsTreatment arm: 320 mg aqueous ALE four times daily. 1280 mg per day.
Control arm: placebo capsules four times daily.
Duration of treatment: 12 weeks
OutcomesTotal cholesterol reduction
HDL cholesterol
LDL cholesterol
Triglycerides
NotesFood diaries reveal that included sample was health-aware, with higher than UK average intake of fruit, dairy, nuts, seeds, whole grain and oily fish.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Patients were randomised using MINIM software (London Hospital Medical College, UK) with minimization for plasma total cholesterol, age and sex"
Allocation concealment (selection bias)Low risk"Treatment groups were coded by a third party and the code was not broken until after data analysis"
Blinding (performance bias and detection bias)
All outcomes
Low risk"Double-blind", "matched placebo"; author communication: "placebo matched for colour and size". "The 'guess the treatment question' revealed that the placebo capsules were not distinguishable from the ALE capsules by volunteers".
Incomplete outcome data (attrition bias)
All outcomes
Low risk

All 4 withdrawals accounted for: 2 participants in placebo group did not start treatment i.e. no baseline/end data available.

2 further withdrawals (1 in each group) due to adverse events unrelated to study medication.

Selective reporting (reporting bias)Low riskResults reported for all main outcome measures.

Englisch 2000

MethodsRandomised, double-blind
2 parallel arms
Participants

143 Caucasian patients aged between 18 and 70 years. Total cholesterol level of greater than 7.3 mmol/L (equivalent to 280 mg/dL).

Treatment arm: n = 71, mean age 54.2 years
Placebo arm: n = 72, mean age 49.7 years

InterventionsTreatment arm: 900 mg artichoke dry extract twice daily. 1800 mg per day.
Control arm: placebo.
Duration of treatment: 6 weeks
OutcomesTotal cholesterol reduction
LDL
HDL
Triglyceride
LDL/HDL ratio
NotesDietary fat intake recorded as high in 11 patients in the treatment arm compared with 30 in the placebo arm.
Significant percentage reduction in total cholesterol levels compared with placebo.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk"Patients were randomly allocated to one of the two treatment groups". No further details provided.
Allocation concealment (selection bias)Unclear riskNo details provided.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskDescribed as double-blind but no details provided.
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients accounted for, ITT analysis. 12 drop-outs due to protocol violations.
Selective reporting (reporting bias)Low riskData for all main outcomes reported.

Petrowicz 1997

  1. a

    ALE Artichoke leaf extract; ITT intention to treat; HDL high-density lipoprotein; LDL low-density lipoprotein; TAG triacylglycerol

MethodsRandomised, double-blind
2 parallel arms
Participants

44 entered / drop outs not reported.
Healthy volunteers, aged 20 - 49 years.

Treatment arm: n = 22
Placebo arm: n = 22

InterventionsTreatment arm: 640 mg artichoke leaf extract three times daily. 1920 mg per day.
Control arm: placebo.
Duration of treatment: 12 weeks.
OutcomesTotal cholesterol reduction
NotesAvailable as abstract only.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk"Randomised", additional communication from author (study protocol): participants were randomised using a computer randomisation list.
Allocation concealment (selection bias)Unclear riskNo details provided.
Blinding (performance bias and detection bias)
All outcomes
Low risk"Double-blind", additional communication from author (study protocol): identical placebo, confirms double-blinding of study.
Incomplete outcome data (attrition bias)
All outcomes
Low riskAccording to communication from author, all participants completed the study.
Selective reporting (reporting bias)High riskOnly data from subgroup analyses and selected outcome measures reported.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Anon 2007Review, contains no additional studies
Anon 2008Review, contains no additional studies
Dog 2003Educational review, no additional studies
Dorn 1995Was not a randomised controlled trial although it was described as a randomised controlled trial
Goetz 2007Plant monograph, contains no trial data
Hausler 2003Overview, no trial data
Joy 2007Review, contains no additional studies
Kirchoff 1994Did not measure blood cholesterol
Kraft 2002Review of Schmiedel 2002
Kupke 1991Did not test an ALE mono-preparation
Lupattelli 2004Uncontrolled trial
Meletis 2003Review, contains no additional studies
Montini 1975Did not test whole artichoke leaf extract
Nazni 2006Not randomised
Pittler 2001Review of Englisch 2000
Rondanelli 2011Did not test an ALE mono-preparation
Schmiedel 2002ALE as part of a treatment package including of different dietary interventions, relaxation therapies, physical therapy.
Springer 2003Review, contains no additional studies
Thompson 2003Review, contains no additional studies
Wolf 1996General conference report, no RCT reported

Ancillary