From:  Antioxidant and anti-inflammatory functional foods for the management of type 2 diabetes: a systematic review

 Results from six meta-analyses of ACNs from fruits and vegetables on glycemic indices, insulin resistance, hyperlipidemia, inflammation, and oxidation in patients with T2DM.

ReferenceNumber of studies/patients includedIntervention/dosage form/doseT2DM outcomesConclusionsStudy limitations
Tiwari et al. [111] (2024)21 RCTs/not statedACN-rich foods, various sources/dose not statedResults of clinical trials showed that ACN-rich foods significantly reduced the FBG, TC, HbA1c, and TG.Consumption of ACN-rich foods improves blood glucose regulation and lipid levels in diabetic and obese subjects.A low number of studies were included in the analysis. Many studies had an unclear risk of bias and were from China and the Middle East, suggesting that they may not be generalizable.
de Oliveira et al. [112] (2023)8 RCTs/n = 390Fresh or freeze-dried blueberries/dose not statedThe study showed no differences in BP, FBG, TC, LDL-C, ApoB, or HbA1c. Decreases in hs-CRP, IL-6. ROS and TNF were reported.Administration of fresh or frozen whole berry products had no significant effect on diabetic parameters, except for reduced inflammation and oxidative stress markers.Analyses only included papers in English or Spanish. Only included studies of whole fruits. Many studies included a high risk of bias.
Mao et al. [113] (2023)13 RCTs/n = 703 T2DMACN-rich extracts/supplements/ 320 mg/dayA study reported that a median ACN dose of 320 mg/day from concentrated fruit extracts or powders significantly reduced FBG, HbA1c, TG, and LDL-C. No significant difference was seen in insulin levels, HOMA-IR, TC, HDL-C, or BP.Significant improvements in glycemic parameters and lipid profiles in patients with T2DM. Concluded that ACNs in fruit extracts or powders were useful in T2DM, to reduce lipid
disorders and resultant cardiovascular diseases.
A low number of studies and subjects were included in the analysis. More than half of the studies had an unclear risk of bias for allocation concealment. Many studies from China and the Middle East indicate that the study may not be generalizable.
Sandoval-Ramírez et al. [114] (2022)5 systematic reviews/meta-analyses/n = 2,314,336 and 8 RCTs/n = 4,984Various ACN-rich products/200 and
400 mg/day
Supplementation with ACNs at doses between 200 and 400 mg/day significantly reduced both FBG (–5.58 mg/dL) and Hb1Ac (–0.65 units).
In T2DM patients, doses of ACNs of 31.45 to 1,050 mg/day reduced the HOMA-IR.
Supplementation with ACNs improved lipid profiles, glycemic indices, and endothelial function, but had no effect on BP.High heterogeneity between disease states, products, populations, and ACN doses. Umbrella reviews limitations include the restriction of the information, limiting the data that can be analyzed.
Fallah et al. [115] (2020)37 RCTs/n = 2,068Various ACN-rich fruit extracts and purified ACNsSignificant reduction in FBG, the 2-hour level PPG (2h-PPG), HbA1c, HOMA-IR, resistin, and PAI-1. No significant change in the levels of fasting insulin or CRP.ACN supplementation for longer than 8 weeks at a high dose of > 300 mg/d significantly reduced levels of FBG, 2h-PPG, HbA1c, and HOMA-IR in patients with T2DM.High heterogeneity as studies included different sources of ACN products, doses, and patient populations. Products also contained other active compounds that may have introduced bias into the study.
Araki et al. [116] (2021)22 RCTs based on ACN structure type/not statedCyanidin-, delphinidin-, or malvidin-based ACNs/wide range of products: juices, fruit, extracts, freeze-dried berries, purified ACNsSignificant reduction in LDL-C cholesterol by delphinidin-based ACNs. Increased HDL-C. No significant effect on fasting glucose levels, insulin levels, HbA1c, or HOMA-IR for any ACN. The insulin resistance index was reduced by cyanidin-based ACNs. No significant effects on glucose levels, insulin levels, HbA1c, or HOMA-IR. TG, LDL-C, and HDL-C levels were significantly improved by delphinidin-based ACNs.
Cyanidin-based ACN products showed improvements in TC and insulin resistance.
Malvidin-based ACNs showed improvement only in HDL-C.
The clinical trials included had low to moderate qualities. Small number of participants, particularly for the individual ACNs trials. The effects of malvidin-based ACNs on glucose related parameters and of cyanidin-based ACNs on HbA1c was not determined due to insufficient data.

ACNs: anthocyanins; BP: blood pressure; CRP: C-reactive protein; FBG: fasting blood glucose; HbA1c: glycated hemoglobin; HDL-C: high-density lipoprotein cholesterol; HOMA-IR: homeostasis model assessment of insulin resistance; LDL-C: low-density lipoprotein cholesterol; PAI-1: plasminogen activator inhibitor-1; PPG: postprandial glucose; RCTs: randomized controlled trials; T2DM: type 2 diabetes mellitus; TC: total cholesterol; TG: triglycerides.