Re: Systematic Review and Meta-analysis of Effects of Artichoke Extracts on Lipid Profile

Artichoke (Cynara cardunculus, Asteraceae) Cholesterol Systematic Review/Meta-analysis Date: 08-15-2017 HC# 071761-574 Sahebkar A, Pirro M, Banach M, Mikhailidis DP, Atkin SL, Cicero AFG. Lipid-lowering activity of artichoke extracts: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. June 2017; [epub ahead of print]. doi: 10.1080/10408398.2017.1332572. Elevated cholesterol is a major risk factor for cardiovascular disease. To prevent and alleviate cardiovascular damage, cholesterol-lowering medication is often recommended. Although there are standard therapies for this purpose, the investigation of botanicals as adjuvant or alternative treatments might provide additional treatment options through which pharmaceutical therapies can be either delayed or avoided altogether. While there have been many studies conducted exploring the lipid-lowering effects of various botanicals, the majority of the studies are short term and small in nature. To that end, preclinical and clinical data collected indicate that artichoke (Cynara cardunculus, Asteraceae) leaf extract (ALE) has potent lipid-lowering and hepatoprotective properties. Scientists think that these properties are likely due to the plant's antioxidants, such as dicaffeoylquinic acid (cynarin and chlorogenic acid), caffeic acid, volatile sesquiterpenes, and flavonoids such as the glycosides luteolin-7-beta-rutinoside (scolymoside), luteolin-7-beta-D-glucoside, and luteolin-4-beta-D-glucoside. Finally, ALE may lower lipid levels by accelerating the excretion rate of fecal bile acids. In fact, ALE has been shown to attenuate hyperlipidemia; however, a previous meta-analysis of three randomized clinical trials revealed study limitations that may have precluded definitive conclusions about artichoke's potential efficacy. This systematic review and meta-analysis addressed whether low-density lipoprotein (LDL) cholesterol would be decreased in those taking ALE. The authors searched PubMed-Medline, Scopus, and ISI Web of Knowledge from inception to March 28, 2017. Search terms included "artichoke," "Cynara cardunculus," and "Cynara scolymus," among others. Inclusion criteria were that trials were randomized, controlled trials (parallel or crossover); investigated "artichoke products" compared with placebo and their impact on plasma or serum lipid concentrations; and measured lipid concentrations both at the start of the study and the end. Trials that were not randomized, did not include a placebo group, were observational, or did not have baseline or endpoint lipid concentrations were excluded. Data extracted from the trials were the first author's name; publication year; country in which the study was conducted; study design; total number of participants and their age, gender, and body mass index; artichoke treatment and dosage; duration; and lipid concentrations at baseline and endpoint. From a total of 66 trials, 18 were subject to inclusion and exclusion criteria, yielding nine that met the criteria for the meta-analysis. These studies contained 702 participants. Those consuming artichoke had a significant decrease in total cholesterol (weighted mean difference [WMD], −17.6 mg/dl; 95% confidence intervals [CI], −22.0, −13.3; P<0.001), LDL cholesterol (WMD, −14.9 mg/dl; 95% CI, −20.4, −9.5; P<0.011), and triglyceride concentrations (WMD, −9.2 mg/dl; 95% CI, −16.2, −2.1; P=0.011). High-density lipoprotein cholesterol was not affected by the treatment. Neither dose nor duration of artichoke supplementation was correlated with plasma LDL cholesterol concentrations. There was a significant correlation of LDL cholesterol in those consuming artichoke and concentrations at baseline (slope, −0.170; 95% CI, −0.288, 0.051; P=0.005). The Cochrane method of bias showed that all studies had low or unclear risk of bias for sequence generation, allocation concealment, selective outcome reporting, other sources of bias, blinding, and incomplete outcome data. Two statistical tests determined that there was little chance of publication bias regarding the LDL cholesterol. This meta-analysis suggests that artichoke consumption may lower total and LDL cholesterol and triglyceride concentrations. Researchers have proposed three potential mechanisms by which artichoke produces its lipid-lowering effects. For example, luteolin interferes with the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the primary enzyme responsible for controlling the rate by which the human body synthesizes its own cholesterol from its precursor mevalonate. Luteolin also interacts with liver sterol regulatory element-binding proteins (SREBPs) and acetyl-CoA C-acetyltransferase (ACAT). The authors further surmise that artichoke's lipid-lowering effects are independent of dosage and duration, and may be associated with baseline LDL concentrations. Discussed limitations include the small sample size of studies and variations in artichoke dosage and concentration. Also, both ALE and concentrated artichoke juice were used in studies, and baseline lipid concentrations were variable. This study suggests that artichoke may be worthy of further study regarding its lipid-lowering bioactivity. —Amy C. Keller, PhD