Effects of a flaxseed-derived lignan supplement on C-reactive protein, IL-6 and retinol-binding protein 4 in type 2 diabetic patients

Elevated C-reactive protein (CRP), IL-6 and retinol-binding protein 4 (RBP4) levels are associated with insulin resistance and diabetes mellitus. Phytoestrogens (including lignans and isoflavones) may enhance the management of diabetes and are hypothesized to act through inflammation pathways. The present study explored the effects of flaxseed-derived lignin on inflammatory factors and RBP4 concentrations intype2 diabetics, who have higher levels of these biomarkers. Seventy community-dwelling diabetic patients (twenty-six men and forty-four post-menopausal women) with mild hypercholesterolaemia completed a randomized, double-blind, placebo-controlled, cross-over trial of supplementation with flaxseed-derived lignan capsules (360 mg/d) or placebo for 12 weeks, separated by an 8-week wash-out period. The participants maintained their habitual diets and levels of physical activity. Baseline to follow-up concentrations of CRP increased significantly within the placebo group (1.42 (SEM 0.19) v. 1.96 (SEM 0.22) mg/l, P<0.001), but were comparatively unchanged in the lignan-supplemented group (1.67 (SEM 0.19) v.1.90 (SEM 0.26) mg/l, P =0.94); a significant difference was observed between treatments  (-0.45 (95% CI -0.76,-0.08) mg/l, P =0.021). This effect was confined to women (P=0.016), but not observed in men (P =0.49). No between-treatment differences were found with regard to IL-6 or RBP4; though IL-6 concentrations increased significantly from baseline to follow-up in both groups (P =0.004 and P<0.001 following lignan and placebo treatments, respectively). The study suggests that lignan might modulate CRP levels in type 2 diabetics. These results need to be confirmed by further large clinical trials of longer duration. (Authors abstract)

Several studies suggest that chronic inflammation, as indicated by elevated levels of inflammatory factors such as C-reactive protein (CRP) and IL-6, plays an important role in the pathogenesis of diabetes mellitus. Retinol-binding protein 4 (RBP4), a protein product of hepatocytes and adipocytes, has also been associated with insulin resistance, diabetes and inflammation. This group has previously shown that a flaxseed-derived lignin supplement moderately decreased glycated Hb levels in type 2 diabetics. The present study is a secondary analysis aimed at exploring the impact of lignan supplementation on CRP, IL-6 and RBP4 levels. The CRP concentrations in the placebo group increased significantly over the study period.  Although CRP levels increased slightly in the lignan-treated group, this increase was not statistically significant.  The present findings of moderate protective effects on CRP are consistent with the results of five previous trials that either tested isolated lignans or isoflavones, flaxseed flour or soya protein. In conclusion, flaxseed lignin may suppress CRP elevation in type 2 diabetics without affecting IL-6 and RBP4 concentrations compared to placebo. Further studies are needed to validate the present results and explore the efficacy of phytoestrogens on inflammatory factors. (Editor's Comments)