Introduction
Obesity has become a global epidemic, with rates tripling since 1975. In 2016, the World Health Organization reported over 1.9 billion overweight adults, with 650 million classified as obese. Obesity is a significant risk factor for various health issues, including type 2 diabetes, cardiovascular diseases, musculoskeletal problems, and certain cancers. Lifestyle modifications, such as diet and exercise, are crucial for both preventing and treating chronic diseases associated with obesity. Quercetin, a flavonoid found in many foods, has been investigated for its potential anti-obesity properties, with inconsistent results. This article examines the current evidence regarding quercetin's role in weight loss, drawing from various research findings and meta-analyses.
What is Quercetin?
Quercetin is a flavonoid, the most abundant of the flavonoids, mainly identified in apples, capers, cocoa powder, berries, red grapes, red wine, citrus fruits, and onion peel. It has been widely investigated for its anti-inflammatory, anti-hypertension, anti-hyperglycemia, anticoagulant, and the improvement of lipid metabolism disorders effects.
Initial Research and Conflicting Results
Experimental and a series of clinical trials have been conducted to assess the anti-obesity properties of quercetin. Results from randomized controlled clinical trials (RCTs) suggested that quercetin supplementation might beneficially affect weight loss; however, as other publications could not replicate the same results.
Meta-Analysis of Clinical Trials
A meta-analysis was conducted to evaluate the effectiveness of quercetin as a weight-loss supplement. The analysis included nine RCTs with a total of 525 participants. Studies were selected from databases including MEDLINE, EMBASE, Google Scholar, and Scopus databases from their inception to August 2018. The following search terms “quercetin” were used in titles and abstracts to find the related studies. No restrictions on the language, publication date, or other filters were applied. Bibliographies of the selected studies and relevant reviews were also checked. Studies were included if they met specific criteria, including adult participants, quercetin intervention for at least two weeks, a placebo or no intervention comparator, and outcomes related to body weight, BMI, waist circumference, and waist-to-hip ratio.
The meta-analysis revealed that daily quercetin supplementation did not significantly affect the body weight (WMD: −0.35 kg, 95% CI: −2.03, 1.33; P=0.68), body mass index (WMD: −0.04 kg/m2, 95% CI: −0.54, 0.45; P=0.87), waist circumference (WMD: −0.37 cm, 95% CI: −1.81, 1.06; P=0.61), and waist to hip ratio (WMD: −0.01, 95% CI: −0.03, 0.01; P=0.48). Subgroup analysis could not identify factors significantly influencing these parameters.
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Study Characteristics and Quality Assessment
The eligible articles were published ranged from 2011 to 2017, and were carried out in Korea, USA, Iran, and Germany. The mean age of participants in each trial ranged from 29.5 to 59.4 years, and the mean BMI ranged from 24.8 to 29.1 kg/m2. The dose of quercetin used varied from 100 to 1,000 mg/day. Five trials were used quercetin-rich onion peel extract capsules, and four trials were used quercetin capsules or tablets. The range of supplementation periods with quercetin was from 2 weeks to 12 weeks. All studies were low risk in at least three domains of the Cochrane collaboration’s tool for assessing the risk of bias and were classified as good quality.
Detailed Findings from Meta-Analysis
The meta-analysis provided a detailed look at the impact of quercetin on various body measurements:
Body Weight: Eight studies (ten treatment arms) with 433 participants assessed the effect of the quercetin on body weight. The overall results demonstrated that quercetin consumption had no significant effect on body weight (WMD =−0.35 kg, 95% CI: −2.03, 1.33, P=0.68), and there was no evidence of between-study heterogeneity (I2=0%).
Body Mass Index (BMI): Eleven treatment arms (including 525 participants) evaluated the effect of quercetin on BMI and were included for pooling. The analysis showed that no significant change was detected for the BMI outcome in participants who followed the quercetin supplementation when compared to the controls (WMD=−0.04 kg/m2, 95% CI: −0.54, 0.45, P=0.87), and no heterogeneity was observed between included studies (I2=0%).
Waist-Hip Ratio (WHR): Two eligible studies reported data on WHR. The meta-analysis revealed that the consumption of quercetin did not significantly influence the WHR (WMD, −0.01, 95% CI, −0.03 to 0.01; P=0.48, I2=58%).
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Waist Circumference (WC): Five studies including a total of 328 participants reported WC as an outcome measure.
Sensitivity and Subgroup Analyses
In the sensitivity analysis, we found no significant difference between the pre- and post-sensitivity pooled WMDs for the weight loss, with a WMD range from −0.47 kg (95% CI, −2.33 to 1.38) to -0.18 kg (95% CI, −1.95 to 1.59). Egger’s test suggested that no significant publication bias for meta-analyses of assessing the effect of quercetin on weight loss (P=0.677) and BMI (P=0.410). There were no statistically significant differences in the pooled effects of quercetin on body weight in the subgroups stratified by types of study design (parallel or crossover design), quercetin dose (≤100 mg/d or ˃100 mg/d), type of intervention (quercetin capsules/tablets or quercetin-rich onion peel extract capsules), gender (male or female or mix), baseline BMI levels (≥25 kg/m2 or ˂25 kg/m2), and intervention duration (≥8 weeks or ˂8 weeks). Similarly, the subgroup analyses indicated that differences in types of study design, quercetin dose, type of intervention, and intervention duration did not appear to significantly influence pooled mean differences in BMI levels. No. No.
Meta-Regression Analysis
The meta-regression results did not indicate any significant association between duration of supplementation and impact of quercetin on body weight (coefficient, −0.09; 95% CI, −0.66 to 0.47; P=0.711) and BMI (coefficient, −0.04; 95% CI, −0.26 to 0.17; P=0.644).
Potential Mechanisms of Action
The crucial role of oxidative stress in the initiation and progression of obesity leads to the hypothesis that antioxidants can be used as therapeutic agents for obesity treatment. Experimental and limited clinical trial evidence supports that quercetin has potential benefit functions on obesity treatment through different molecular pathways. Research suggested that quercetin-induced lipolysis of adipocytes in a dose- and time-dependent manner by increasing cyclic adenosine monophosphate levels and hormone-sensitive lipase activity. Moreover, quercetin also can inhibit adipogenesis by decreasing gene expression levels of the key adipogenic factors peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α . Later reports have shown that quercetin works to block adipogenesis actions through stimulating the MAPK signal pathway.
Animal Studies: Quercetin and Weight Management in Rats
Additional studies have explored the effects of quercetin on weight gain, caloric intake, and feed efficiency in rats, both with and without exercise.
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One study divided Wistar rats into four groups: quercetin-exercise training (QT), quercetin-sedentary (QS), placebo-exercise training (PT), and placebo-sedentary (PS). Rats were exercised and/or orally supplemented with quercetin (25 mg · kg−1 on alternate days) during six weeks. Weight gain of the QT group decreased when compared with the PT and PS groups. Exercised groups increased cumulative caloric intake during the experimental period. The QT group rats also reduced their feed efficiency when compared with the QS and PS groups.
The results indicate that six weeks of exercise did not reduce body WG in lean rats fed with maintenance caloric chow. Although there was a lower WG in the QT group when compared with QS and PS groups, no effect was found between quercetin and placebo groups. Moreover, feed efficiency was lower in the QT group than in the QS and PS groups, but no quercetin effect was also found. It must be highlighted that exercise increased CI in both supplemented and non-supplemented groups.
Quercetin's Impact on Adipogenesis and Neovascularization
Limited studies reported that quercetin inhibited adipogenesis and neovascularization by inhibiting matrix metalloproteinases (MMPs) activity, but such mechanisms have not been elucidated in animal experiments. Five-wk-old C57BL/6J mice were fed a normal diet (ND), HFD, HFD containing 0.05% of quercetin (HFQ0.05), or HFD containing 0.15% of quercetin (HFQ0.15) for 16 wks. Glycerol-3-phosphate dehydrogenase (GPDH) activity was measured using a commercial kit. The mRNA expressions of transcription factors related to adipocyte differentiation were determined by real-time polymerase chain reaction (PCR).
Quercetin intake reduced body weight gain and epididymal adipose tissue weights (P < 0.05). GPDH activity was higher in the HFD group than in the ND group but lower in the quercetin groups (P < 0.05). The mRNA expressions of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, peroxisome proliferator-activated receptor γ, and fatty acid-binding protein 4 were lower in the quercetin groups than in the HFD group (P < 0.05).
Quercetin and Metabolic Syndrome
Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities including central obesity, glucose intolerance, hypertension, and atherogenic dyslipidemia, which together greatly increase the risk for cardiovascular disease or type 2 diabetes. One study examined the effect of oral quercetin administration on morphometric and metabolic parameters associated with MetS as well as the transcriptomic profiles of the liver and retroperitoneal fat tissue.
Adult male rats of the PD/Cub (PD hereafter) strain were held under temperature- (23°C) and humidity- (55%) controlled conditions on 12-h light/12-h dark cycle and fed a laboratory chow diet (STD, ssniff RZ, ssniff Spezialdiäten GmbH, Soest, Germany). At all times, the animals were given free access to food and water. At the age of 12 months, the animals were randomly divided into two groups (n = 6/group). Over the period of 2 weeks, the control group was fed a high-sucrose diet (HSD, protein (19.6 cal%), fat (10.4 cal%), carbohydrates (sucrose, 70 cal%) prepared by Institute for Clinical and Experimental Medicine, Prague, Czechia; PD rats), (26) while the experimental group was fed a HSD fortified with quercetin (10 g quercetin/kg food) (Sigma-Aldrich; PD-Q rats).
The levels of fasting blood glucose did not differ between PD and PD-Q rats. However, during the oral glucose tolerance test, PD-Q rats showed lower blood glucose level at the 180th min. The levels of adiponectin and free fatty acids did not differ between PD and PD-Q rats. The level of triglycerides (TG) greatly decreased in the serum as well as in the liver of rats treated with quercetin.
Quercetin as an Anti-Inflammatory Agent
At the core of most of quercetin’s remarkable properties is its ability to modulate inflammation. The rampant rise of overweight and obesity poses one of the greatest global health threats today. Scientists are now eagerly exploring quercetin’s potential as a means of controlling fat accumulation. In a form of epidemiological detective work, nutrition scientists from Michigan State University explored the impact of dietary flavonoids such as quercetin in their more general roles as systemic anti-inflammatory agents. They found that higher flavonoid intake was associated with lower CRP levels-and quercetin headed the list of specific flavonoid compounds that had the strongest protective effect.