Twelve-Week Mediterranean Diet Intervention Increases Citrus Bioflavonoid Levels and Reduces Inflammation in People with Type 2 Diabetes Mellitus

Abstract

The benefits of a Mediterranean Diet (MedDiet) in the management of diabetes have been reported, but the contribution of polyphenol-rich citrus fruit has not been studied widely. Here, we report the sub-study findings of a previously conducted MedDiet intervention clinical trial in patients with type 2 diabetes mellitus (T2DM), where we aimed to measure the diet intervention effects on plasma citrus bioflavonoids levels and biomarkers of inflammation and oxidative stress. We analysed plasma samples from 19 (of original 27) participants with T2DM who were randomly assigned to consume the MedDiet intervention or their usual diet for 12 weeks and then crossed over to the alternate diet. Compared with baseline, MedDiet significantly increased levels of the citrus bioflavonoids naringin, hesperitin and hesperidin (by 60%, 58% and 39%, respectively, p < 0.05) and reduced plasma levels of the pro-inflammatory cytokine IL-6 (by 49%, p = 0.016). Oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased by 32.4% (p = 0.128). Usual diet did not induce these beneficial changes. The reduced inflammatory profile of T2DM participants may, in part, be attributed to the anti-inflammatory actions of citrus bioflavonoids. Together with indications of improved oxidative stress, these findings add to the scientific evidence base for beneficial consumption of citrus fruit in the MedDiet pattern.

Keywords: citrus bioflavonoids; dipeptidyl peptidase-4; inflammation; oxidative stress; type 2 diabetes mellitus.

Figure 1

Effect of 12-weeks Mediterranean diet intervention (blue bars) or usual diet (orange bars) on citrus bioflavonoid levels compared with baseline levels (grey bars) in participants with Type 2 diabetes. Sample size: N = 18 for naringenin, naringin, hesperidin, hesperitin; N = 9 for rutin. Data are mean ±SEM. * p < 0.05, different from baseline; # p < 0.05, different from usual diet.

Figure 2

Effect of 12-week Mediterranean diet intervention (blue bars) or usual diet (orange bars) on glycaemic status compared with baseline levels (Grey bars) in participants with type 2 diabetes. Sample size, N = 19. Data are mean ± SEM. HbA1c, haemoglobin A1c; DDP4, dipeptidyl-peptidase 4. For insulin (1 µIU/mL = 6.945 pmol/L).

Figure 3

Effect of 12-week Mediterranean diet intervention (blue bars) or usual diet (orange bars) on plasma levels of pro-inflammatory cytokine interleukin-6 (IL-6) and oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) compared with baseline levels (Grey bars) in participants with type 2 diabetes. Sample size, N = 19. Data are mean ± SEM. * p < 0.05, different from baseline.