Efficacy of Myricetin Supplementation on Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis of In Vivo Mice Studies

Abstract

Background/objectives: Type 2 diabetes mellitus (T2DM) is a disorder characterized by insulin resistance, hyperglycemia, and dyslipidemia. Myricetin, a flavonoid found in various plants, has shown potential anti-diabetic effects in murine studies. This meta-analysis aimed to evaluate the impact of myricetin supplementation on glucose metabolism and lipid profiles in mouse models of metabolic diseases.

Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines (PROSPERO: CRD42024591569). Studies involving mice with metabolic disease models and exclusively using myricetin supplementation were checked across four databases (Embase, Scopus, PubMed, and WoS) until 23rd September 2024. The primary outcomes assessed were blood glucose (BG), insulin levels, triacylglycerol (TAG), total cholesterol (TC), HDL, and LDL. A random-effects model was applied to estimate standardized mean differences (SMD), and SYRCLE's risk-of-bias tool for animal studies was used.

Results: Twenty-one studies with 514 mice met the inclusion criteria. Myricetin supplementation significantly reduced BG (SMD = -1.45, CI: -1.91 to -0.99, p < 0.00001, I² = 74%), insulin (SMD = -1.78, CI: -2.89 to -0.68, p = 0.002, I² = 86%), TAG (SMD = -2.60, CI: -3.24 to -1.96, p < 0.00001, I² = 81%), TC (SMD = -1.86, CI: -2.29 to -1.44, p < 0.00001, I² = 62%), and LDL (SMD = -2.95, CI: -3.75 to -2.14, p < 0.00001, I² = 74%). However, the effect on HDL was not statistically significant (SMD = 0.71, CI: -0.01 to 1.43, p = 0.05, I² = 83%).

Conclusions: Myricetin supplementation improved glucose metabolism and lipid profiles in mouse models, suggesting its potential as a therapeutic agent for managing T2DM. However, further research is needed to confirm these findings in human studies.

Keywords: 3,3′,4′,5,5′,7-hexahydroxyflavone; animal studies; antihyperglycemic; antihyperlipidemic; cardiometabolic health; dyslipidemia; insulin resistance.

Figure 1

Chemical structures of myricetin (A) and dihydromyricetin (B).

Figure 2

PRISMA flowchart illustrating study selection process for meta-analysis inclusion.

Figure 3

The risk of bias in the included studies evaluated using SYRCLE’s risk-of-bias tool for animal studies: sequence generation (1), baseline characteristics (2), allocation concealment (3), random housing (4), blinding of performance bias (5), blinding of detection bias (6), random outcome assessment (7), incomplete outcome data (8), selective outcome reporting (9), and other potential sources of bias (10), [16,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43].

Figure 4

Forest plot representation of included studies evaluating the impact of myricetin supplementation on blood glucose (A) [25,27,28,29,32,33,34,35,36,37,38,39,40,41,42] and insulin levels (B) [27,28,32,33,34,36,38].

Figure 5

Forest plot representation of included studies evaluating the impact of myricetin supplementation on triacylglycerol (A) [16,23,24,26,27,28,29,30,31,32,33,34,35,36,38,41] and total cholesterol levels (B) [16,23,24,27,28,30,31,32,33,34,35,36,38,41].

Figure 6

Forest plot representation of included studies evaluating the impact of myricetin supplementation on LDL-cholesterol (A) [16,24,30,32,33,35,36,38,41] and HDL-cholesterol levels (B) [16,24,27,28,30,32,33,36,41].

Figure 7

Molecular mechanisms of myricetin in regulating both glucose and lipid metabolism. On the glucose metabolism side, insulin sensitivity and glucose uptake are enhanced through the upregulation of key molecules such as GLUT2, GLUT4, PKB, and IRS-1, while DPP-4 is reduced and GLP-1 levels are increased. These actions lead to improved insulin signaling and glucose utilization. In lipid metabolism, PPARα is activated, SREBPs are suppressed, oxidized LDL (ox-LDL) cholesterol is reduced, and CD36 expression is downregulated, resulting in increased fat breakdown and reduced fat storage, triglycerides (TAG), total cholesterol (TC), and hepatic cholesterol (CH).