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

ABSTRACT 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.

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Available from: An Pan, Sep 26, 2015
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    • "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. "
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    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.
    Journal of nutrition and metabolism 10/2012; 2012(2):585170. DOI:10.1155/2012/585170
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    • "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. "
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    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.
    Nutrition Journal 05/2011; 10(1, article 44):44. DOI:10.1186/1475-2891-10-44 · 2.60 Impact Factor
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    • "; Pan et al. (2009) (54) 360 mg/d from lignan capsules Supplementation reduced HbA1C compared with placebo in participants with type 2 diabetes (53) Compared with placebo, increases in CRP from baseline to follow-up were lower with supplementation (54) Hallund et al. (2006) (47) ; Hallund et al. (2008) (48) ; Hallund et al. (2006) (49) 500 mg/d from flax lignan complex No significant effects were seen on plasma lipids, glucose or markers of oxidative stress among the healthy participants (47,49) except that increases in CRP from baseline to follow-up were lower with supplementation compared with placebo (48) Spence et al. (2003) (46) 222 mg/d from low-lignan, high-a-linolenic acid flaxseed 270 mg/d from flaxseed intermediate in SDG and a-linolenic acid 450 mg/d from high-lignan, low-a-linolenic acid flaxseed Compared with baseline, all dosages reduced blood pressure during mental stress. The highest dosage was associated with the least increase in peripheral resistance, greatest reduction in cortisol and smallest increase in fibrinogen during stress containing 0·5 or 1·0 % SDG resulted in significantly reduced visceral fat gain. "
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    ABSTRACT: Flaxseed is the richest source of the lignan secoisolariciresinol diglucoside (SDG). After ingestion, SDG is converted to secoisolariciresinol, which is further metabolised to the mammalian lignans enterodiol and enterolactone. A growing body of evidence suggests that SDG metabolites may provide health benefits due to their weak oestrogenic or anti-oestrogenic effects, antioxidant activity, ability to induce phase 2 proteins and/or inhibit the activity of certain enzymes, or by mechanisms yet unidentified. Human and animal studies identify the benefits of SDG consumption. SDG metabolites may protect against CVD and the metabolic syndrome by reducing lipid and glucose concentrations, lowering blood pressure, and decreasing oxidative stress and inflammation. Flax lignans may also reduce cancer risk by preventing pre-cancerous cellular changes and by reducing angiogenesis and metastasis. Thus, dietary SDG has the potential to decrease the incidence of several chronic diseases that result in significant morbidity and mortality in industrialised countries. The available literature, though, makes it difficult to clearly identify SDG health effects because of the wide variability in study methods. However, the current evidence suggests that a dose of at least 500 mg SDG/d for approximately 8 weeks is needed to observe positive effects on cardiovascular risk factors in human patients. Flaxseed and its lignan extracts appear to be safe for most adult populations, though animal studies suggest that pregnant women should limit their exposure. The present review discusses the potential health benefits of SDG in humans, with supporting evidence from animal studies, and offers suggestions for future research.
    The British journal of nutrition 12/2009; 103(7):929-38. DOI:10.1017/S0007114509992753 · 3.45 Impact Factor
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