Reviewed: Rondanelli M, Giacosa A, Opizzi A, et al. Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. Int J Food Sci Nutr. February 2013;64(1):7-15.

Cardiovascular disease (CVD) is a prevalent worldwide threat to health. Nutritional modifications, such as low-fat diets, typically are used to prevent or lessen CVD risk. However, diets targeting the reduction of harmful low-density lipoprotein (LDL) cholesterol also may reduce the concentration of beneficial high-density lipoprotein (HDL) cholesterol. Thus, interventions that reduce LDL while promoting higher concentrations of HDL are necessary for the alleviation of CVD. Artichoke (Cynara scolymus, Asteraceae) leaf extract (ALE) has been shown to lower cholesterol in previous studies. This randomized, double-blind, placebo-controlled study investigated the effects of eight weeks of ALE supplementation on HDL, LDL, and total cholesterol concentrations in subjects with hypercholesterolemia.

The 92 study participants were “mildly” hypercholesterolemic (5.4-7.0 mmol/l), 18 to 60 years of age, had a body mass index (BMI) range from 19 to 30 kg/m², and were recruited from the University of Pavia in Pavia, Italy. They did not have CVD or chronic diseases and were not on medicine that targeted cholesterol concentrations. The study excluded those who smoked tobacco, consumed excessive amounts of alcohol or weight-loss drugs, or were pregnant, lactating, or in menopause. Subjects were instructed to maintain their normal level of exercise and a three-day baseline dietary assessment was taken. This information was used to standardize subjects’ diets to total caloric levels similar to American Heart Association recommendations; diet also was evaluated at the end of the study.

Blood pressure, body weight, and BMI, as well as skinfold thickness and abdominal diameter, were measured both at the beginning and at the end of the study. Treatments consisted of 250 mg tablets of either ALE or “a matching placebo” (excipients without ALE) administered before lunch and dinner (500 mg total daily dosage) for eight weeks. ALE was standardized to contain more than 20% caffeoylquinic acids, 5% flavonoids, and 5% cynaropicrin. [Note: No description of the placebo is given.] Both the ALE and placebo tablets were supplied by Indena SpA; Milan, Italy. Leftover tablets were used to gauge compliance.

Fasting LDL, HDL, total cholesterol, and glucose concentrations were measured from blood samples taken at baseline and the study endpoint. Fasting HDL cholesterol also was assessed eight weeks after the study’s conclusion. Tolerability of the treatments was estimated by blood pressure and blood chemistry at baseline and at the end of the study. Any adverse side effects were inquired about by investigators and reported by subjects.

Of the subjects enrolled, there were no dropouts reported and all participants — 46 in each group — completed the study. Blood pressure measurements of both groups were within a normal range at baseline and endpoint, and BMI did not significantly change in either group during the study. Beneficial HDL cholesterol levels, the primary endpoint, significantly increased in the ALE group (P<0.001), but remained unchanged in the placebo group. No significant changes were observed in blood glucose concentrations in either group. Total cholesterol was significantly lower in both the supplemented (P<0.001) and control (P<0.010) groups; the change in this parameter in the supplemented group was significantly greater than in the control group (P=0.012).

In addition, the total cholesterol-to-HDL cholesterol ratio at the end of the study was significantly lowered in the supplemented group as compared to baseline (P<0.001); no change was observed in the placebo group. The LDL cholesterol concentrations also were significantly lowered in both the supplemented and placebo groups (P<0.001 and P<0.05, respectively). In the supplemented group, the LDL cholesterol-to-HDL cholesterol ratio significantly decreased (P<0.001), but remained unchanged in the placebo group. Triglycerides were not significantly altered in either group. Compliance was rated as “excellent,” and no adverse side effects were reported. In addition, blood chemistry was normal in all subjects both at baseline and endpoint of the study.

In conclusion, this study reports a significant increase in HDL cholesterol with a concurrent decrease in LDL cholesterol in patients with hypercholesterolemia after eight weeks of supplementation with ALE. The authors note that an inverse relationship exists between HDL cholesterol and CVD risk, with a three percent reduction in death risk or myocardial infarction for every one percent increase in HDL cholesterol. Therefore, the clinical applications of ALE for this purpose may be beneficial, but warrant further study.

Possible mechanisms for the observed bioactivity include the modulation of various enzymatic activities by ALE compounds. For example, previous studies have shown that the ALE compounds chlorogenic acid and luteolin possibly attenuate LDL cholesterol oxidation and related damage. Luteolin, in addition, inhibits coenzyme A reductase activity, which is a key enzyme in the liver cholesterol synthesis pathway. Finally, chlorogenic acid could favor the HDL cholesterol increase through the agonistic effect on paraxonase-1, which is involved in the protection of HDL cholesterol from oxidation.

One important avenue of future research into ALE is the investigation of gender-related effects, as certain parameters measured — HDL cholesterol, in particular — have shown differences when data is stratified by gender. This suggests potential variable responses to ALE supplementation. Furthermore, given the marked sensory properties of cynaropicrin (bitter) and cynarin (sweet aftertaste), more information on the nature of the placebo should have been included in the publication.