Re: Artichoke Leaf Extract Improves Triglyceride Levels in Women with Metabolic Syndrome who Carry the A Allele Genotype of FTO-rs9939609

Rezazadeh K, Rahmati-Yamchi M, Mohammadnejad L, Ebrahimi-Mameghani M, Delazar A. Effects of artichoke leaf extract supplementation on metabolic parameters in women with metabolic syndrome: Influence of TCF7L2-rs7903146 and FTO-rs9939609 polymorphisms. Phytother Res. January 2018;32(1):84-93. doi: 10.1002/ptr.5951. Metabolic syndrome (MetS) significantly increases the risk of cardiovascular disease and diabetes. MetS is diagnosed when a person has at least three of the following conditions: elevated blood glucose, high blood pressure, low levels of high density lipoprotein cholesterol (HDL-c), high levels of low density lipoprotein cholesterol (LDL-c), and abdominal obesity. The rs7903146 intron of the transcription factor 7-like 2 (TCF7L2) gene and the rs9939609 intron of the fat mass and obesity-associated (FTO) gene have single-nucleotide polymorphisms (SNP) that are associated with increased risk of MetS. In animal and in vitro studies, artichoke (Cynara cardunculus Scolymus Group, Asteraceae) leaf extract (ALE) has been found to improve lipid and glucose metabolism, but the results of ALE clinical trials have been inconsistent. The purpose of this parallel, randomized, double-blind, placebo-controlled clinical trial was to evaluate the influence of TCF7L2-rs7903146 and FTO-rs9939609 polymorphisms on metabolic response to ALE supplementation in women with MetS. Women (n=56) with MetS were recruited through clinician referral and printed advertisements. The MetS criteria used were HDL < 50 mg/dL, fasting blood sugar (FBS) ≥ 100 mg/dL, systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 85 mmHg, triglycerides (TG) ≥ 150 mg/dL, and waist circumference (WC) ≥ 95 cm. Exclusion criteria included the presence of sprue (a disease of tropical regions that is of unknown cause and is characterized by fatty diarrhea and malabsorption of nutrients), Crohn's disease, liver dysfunction, gallstones, biliary tract obstruction, inflammatory disease, hypo- or hyperthyroidism, cancer, renal failure, diabetes mellitus, cardiovascular disease, or recent surgery. Participants were also excluded if they used antioxidant supplements, corticosteroids, or medications to reduce blood pressure or lipids during the preceding three months, or if they were on a weight loss diet, had an allergy to artichoke, were pregnant or lactating, or going through menopause. The study took place in Khoy, Iran from November 2014 to May 2015. The Dineh Iran Co in Qazvin, Iran prepared the 70% ethanol ALE containing 4-5% chlorogenic acid from artichoke leaves provided by "Iran's medicinal plants cultivation company." Each ALE tablet contained 450 mg ALE. The placebo tablet contained 450 mg of inactive ingredients including corn (Zea mays, Poaceae) seed starch, lactose, and avicel. Patients were randomly allocated to the ALE or placebo group. Both groups took four tablets a day (one before breakfast, two before lunch, and one before dinner) for a total of 1800 mg/day for 12 weeks. Patients were advised to continue with their usual physical activity and diets. At baseline and at study's end, blood pressure and anthropometric data were collected, blood samples were drawn, and patients completed three 24-hour food diaries to assess dietary intake and the International Physical Activity Questionnaire to measure physical activity. Blood samples were analyzed to determine the following: FBS, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), TG, total cholesterol (TC), LDL-c, and HDL-c. Deoxyribose nucleic acid (DNA) was extracted and the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used to genotype SNPs of TCF7L2-rs7903146 and FTO-rs9939609. Dietary intake, physical activity, and anthropomorphic characteristics did not significantly differ between the groups at baseline except that the ALE group had a significantly higher mean weight (P = 0.005) and mean body mass index (P = 0.012). The incidence of the TT and C alleles of TCF7L2-rs7903146 and the A and TT alleles of FTO-rs9939609 did not significantly differ between groups. Of the 56 recruited patients, three were lost from the interventional group due to irregular supplement consumption (n=1), and hypothyroidism (n=2). Four were lost from the placebo group due to use of medication for high blood pressure (n=2), and discontinuation of placebo (n=2). No adverse events were reported. Within group analyses showed that metabolic responses to ALE supplementation did not significantly differ between C allele and TT allele carriers of TCF7L2rs7903146. After adjusting for baseline values, within group analysis showed that ALE supplementation significantly decreased serum TG levels in patients with the A allele of FTO-rs9939609 (P < 0.05). The other anthropometric and biochemical indices did not significantly differ between the A and TT allele carriers. After controlling for the confounding effects of body mass index and physical activity level, the results did not change significantly. The authors conclude that "ALE supplementation may improve serum triglyceride level in A allele genotype of FTO-rs9939609 polymorphism in women with MetS." The trial was limited by its small sample size, relatively short duration, and the study of women only. Larger, long-term, randomized clinical trials are needed to better understand genotypical differences in the metabolic response to ALE supplementation. The authors declare no conflict of interest. —Heather Anderson, MD