Efficacy of flavonoids-containing supplements on insulin resistance and associated metabolic risk factors in overweight and obese subjects: a systematic review and meta-analysis of 25 randomized controlled trials

Abstract

Background: Obesity is becoming a global epidemic. Flavonoids, with anti-inflammatory and antioxidative functions, are proposed to treat insulin resistance (IR) in obese subjects. We aimed to evaluate the effectiveness and safety of flavonoids-containing supplements on IR and associated metabolic risk factors in overweight and obese participants.

Methods: Randomized controlled trials (RCTs) involving flavonoids-containing supplements used to treat overweight and obese subjects with results of IR, other associated metabolic risk factors, and adverse effects published were retrieved from 5 electronic databases from the year of inception to January 2, 2022.

Results: Twenty-five RCTs (n = 1950) were included. Pooled results demonstrated that HOMA-IR in the group receiving flavonoids-containing supplements significantly decreased versus the control group (WMD = -0.132, 95% CI: -0.236 to -0.027, p = 0.013). Subgroup analyses showed that HOMA-IR in the subgroup receiving flavonoid-containing mixtures significantly decreased (WMD = -0.25, 95% CI: -0.43 to -0.06, p = 0.008), whereas such result was not found in the singly-used flavonoids subgroup (WMD = -0.08, 95% CI: -0.20 to 0.05, p = 0.240). In addition, QUICKI in the experimental group had an increasing trend compared to that in the control group (WMD = 0.01, 95% CI: -0.00 to 0.02, p = 0.065). For secondary outcomes, FBG, FBI, TC, TG, SBP, weight, BMI, and WHR in the group receiving flavonoids-containing supplements dropped significantly compared to those in the controls (WMD = -0.05, 95% CI: -0.08 to -0.02, p = 0.002; WMD = -0.58, 95% CI: -1.04 to -0.12, p = 0.014; WMD = -0.04, 95% CI: -0.06 to -0.03, p < 0.001; WMD = -0.04, 95% CI: -0.05 to -0.03, p < 0.001; WMD = -2.01, 95% CI: -3.17 to -0.86, p = 0.001; WMD = -0.29, 95% CI: -0.49 to -0.09, p = 0.004; WMD = -0.10 95% CI: -0.17 to -0.04, p = 0.003; WMD = -0.10, 95% CI: -0.01 to -0.00, p = 0.015; respectively). Adverse reactions did not differ between the group receiving flavonoids-containing supplements and the control group (RR = 0.97, 95% CI: 0.62 to 1.52, p = 0.905).

Conclusion: This study showed that flavonoids-containing supplements may be efficacious and safe in improving IR and associated metabolic risk factors in overweight and obese participants. Nevertheless, doubt over the findings remains because limited RCTs per type of flavonoids-containing supplement were investigated, and many of the RCTs had a small sample size. Therefore, the findings must be validated in future research.

Systematic review registration: https://inplasy.com/inplasy-2022-2-0011/, identifier INPLASY202220011.

Keywords: Flavonoids; insulin resistance; meta-analysis; obesity; overweight; systematic review.

Figure 1

Flow diagram of study selection.

Figure 2

Risk of bias assessment in the included studies.

Figure 3

Effects of flavonoids-containing supplements on HOMA-IR in overweight and obese subjects.

Figure 4

Effects of flavonoids-containing supplements on QUICKI in overweight and obese subjects.

Figure 5

Effects of flavonoids-containing supplements on fasting blood glucose.

Figure 6

Effects of flavonoids-containing supplements on fasting blood insulin.

Figure 7

Effects of flavonoids-containing supplements on weight.

Figure 8

Effects of flavonoids-containing supplements on body mass index.

Figure 9

Effects of flavonoids-containing supplements on waist circumference.

Figure 10

Effects of flavonoids-containing supplements on waist-to-hip ratio.

Figure 11

Publication bias analysis. (A) homeostasis model assessment of insulin resistance, (B) fasting blood glucose (C) fasting blood insulin, (D) total cholesterol, (E) triglycerides, (F) high-density lipoprotein cholesterol, (G) low-density lipoprotein cholesterol, (H) systolic blood pressure, (I) diastolic blood pressure, (J) weight, (K) body mass index, and (L) waist circumference.