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

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, 294 Tai-Yuan Road, Shanghai 200031, China
The British journal of nutrition (Impact Factor: 3.45). 09/2008; 101(8):1145-9. DOI: 10.1017/S0007114508061527
Source: PubMed


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 lignan on inflammatory factors and RBP4 concentrations in type 2 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.

Download full-text


Available from: An Pan
    • "Ox-LDL, a risk factor of CVD, was also reduced by a high-lignan diet (Almario and Karakas, 2013). Other studies have demonstrated improved glycemic control (Pan et al., 2007), decreased blood glucose levels (Zhang et al., 2008), reduced CRP (Hallund, Tetens, Bugel, Tholstrup, and Bruun, 2008; Pan et al., 2009) and a mild attenuation in DBP (Cornish et al., 2009) with a lignan-supplemented diet. An additional study noted that Beneflax, a lignan supplement containing 543 mg/day of flaxseed lignan per tablet (Cornish et al., 2009), does not pose a risk for hypotension or hypoglycemia in healthy older adults (Billinsky et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dietary flaxseed is being studied as an alternative or complementary therapy to medications for reducing risk factors related to cardiovascular disease progression. The suggested benefits of alpha-linolenic acid (ALA) as an antihypertensive agent, of secoisolariciresinol diglucoside (SDG) derived enterolignans as antioxidants and estradiol mimetics and dietary fiber for its role in cholesterol lowering are just some of the potential benefits of consuming flaxseed. These studies have progressed from dietary studies involving animal models to large-scale clinical trials with the ultimate goal of adopting its consumption by the general public. To promote adherence in long-term clinical trials and encourage its consumption by the general public, flaxseed in one of its various forms or as its isolated bioactive ingredients is either incorporated into food products, called functional foods, or sprinkled onto foods before consumption. The stability of these bioactives in any of these forms becomes crucial for its acceptance by these populations and in order to optimize its biological actions. The effects of the food matrix, food preparation processes and storage conditions are all factors that can influence bioactive stability and are discussed here.
    No preview · Article · Aug 2015 · Food Research International
  • Source
    • "Pan et al. (2009 [34]) administering FLC (360 mg SDG/day) to type 2 diabetics for 12 weeks in a study of similar design to the current study found that CRP level rises were reduced relative to placebo and there were no treatment changes in IL-6 or TNF-α relative to placebo (again uncorrected for multiple comparisons). It may also be that the somewhat higher CRP and IL-6 levels in the current study as compared to those reported by Pan et al. (2009 [34]) caused their amenability to be greater. While these CRP and IL-6 statistically significant differences disappeared due to adjustment for multiple comparisons it should be pointed out that a number of studies have shown that FLCs reduce CRP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim. Animal and human study evidence supports the hypothesis that flaxseed lignan complex (FLC) at a dose of 600 mg secoisolariciresinol diglucoside (SDG)/day for three months would combat hyperglycaemia, dyslipidemia, blood pressure, central obesity, prothrombotic state, inflammation, and low density lipoprotein (LDL) oxidation. Methods. Sixteen type 2 diabetic patients completed this double-blind, randomised crossover placebo-controlled study. A univariate repeated measures analysis of covariance (significance P < 0.05) was followed by a mixed linear model effects analysis corrected for multiple comparisons (MCC). Results. Prior to MCC, FLC caused decreased fasting plasma glucose, A1c, inflammation (c-reactive protein (CRP) and interleukin-6 (IL-6)), and increased bleeding time. After correction for multiple comparisons, FLC induced a statistically significant increase in bleeding time and smaller waist circumference gain. No treatment effect occurred in the other variables before or after adjustment. Conclusions. It is concluded that FLC significantly increased bleeding time thus reducing the prothrombotic state, reduced central obesity gain as measured by waist circumference, and did not affect significantly the other dependent variables measured after adjustment for multiple comparisons. These findings, not yet published in human type 2 diabetes, suggest that this FLC dose over at least three months, may, subject to further investigation, reduce polypharmacy.
    Full-text · Article · Oct 2012 · Journal of nutrition and metabolism
  • Source
    • "The results suggest that these obese participants did not have low grade systemic inflammation, but these participants are classified as a high cardiovascular disease risk group [39]. Studies show that CRP concentration remained the same following flaxseed or flaxseed lignan supplementation while CRP concentration in the control supplementation group increased [29,30,40,41]. A similar result was found in the present study. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.
    Full-text · Article · May 2011 · Nutrition Journal
Show more