Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial

BackgroundFlaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients.
Methodology/Principal FindingsThis was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA1c (-0.10±0.65 % vs. 0.09±0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2±18.1 vs. 1.2±2.4 µg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations.
Conclusions/SignificanceDaily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes.
Trial RegistrationClinicalTrials.gov NCT00363233

**背景** 已有研究证实，食用亚麻籽可改善人类血脂水平，而亚麻籽来源的木脂素（flaxseed-derived lignan）可在动物模型中增强血糖调控能力。本研究旨在探讨亚麻籽来源木脂素补充剂对2型糖尿病患者血糖调控、血脂谱及胰岛素敏感性的影响。
**方法与主要结果** 本研究为随机双盲安慰剂对照交叉试验，于2006年4月至12月在中国上海开展。共纳入73例伴轻度高胆固醇血症的2型糖尿病患者。受试者被随机分配接受亚麻籽木脂素胶囊（每日摄入360mg木脂素）或安慰剂干预，为期12周，两组干预间隔8周洗脱期。研究期间检测受试者的糖化血红蛋白（HbA1c）、血脂谱、胰岛素抵抗指数及炎症因子水平。最终68例患者完成全程研究并纳入数据分析。与安慰剂组相比，木脂素补充剂组通过糖化血红蛋白评估的血糖调控水平得到显著改善（-0.10±0.65% vs 0.09±0.52%，P=0.001）；但两组受试者的空腹血糖、胰岛素浓度、胰岛素抵抗及血脂谱均未出现显著变化。木脂素干预后，受试者尿液中木脂素代谢物肠二醇（enterodiol）和肠内酯（enterolactone）的排泄量较基线水平显著升高（14.2±18.1 vs 1.2±2.4 μg/mL，P<0.001）。尿液排泄浓度检测结果还显示，木脂素与异黄酮（isoflavones）在生物利用度方面几乎不存在竞争关系。
**结论与意义** 每日补充木脂素可使2型糖尿病患者的血糖调控得到小幅但具有统计学意义的改善，且未对空腹血糖、血脂谱及胰岛素敏感性产生明显影响。未来仍需开展更多研究以验证本研究结果，并探讨木脂素对2型糖尿病的治疗潜力。
**试验注册** ClinicalTrials.gov NCT00363233