Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial

An Pan, Jianqin Sun, Yanqiu Chen, Xingwang Ye, Huaixing Li, Zhijie Yu, Yanfang Wang, Wenjia Gu, Xinyi Zhang, Xiafei Chen, Wendy Demark-Wahnefried, Yong Liu, Xu Lin, An Pan, Jianqin Sun, Yanqiu Chen, Xingwang Ye, Huaixing Li, Zhijie Yu, Yanfang Wang, Wenjia Gu, Xinyi Zhang, Xiafei Chen, Wendy Demark-Wahnefried, Yong Liu, Xu Lin

Abstract

Background: Flaxseed 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 findings: This 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 HbA(1c) (-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 microg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations.

Conclusions/significance: Daily 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 registration: ClinicalTrials.gov NCT00363233.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Study flow chart of the lignan intervention trial.

References

    1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21:1414–1431.
    1. Kaur J, Singh P, Sowers JR. Diabetes and cardiovascular diseases. Am J Ther. 2002;9:510–515.
    1. Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care. 1998;21:160–178.
    1. Duncan AM, Phipps WR, Kurzer MS. Phyto-oestrogens. Best Pract Res Clin Endocrinol Metab. 2003;17:253–271.
    1. Bhathena SJ, Velasquez MT. Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr. 2002;76:1191–1201.
    1. Cunnane SC, Hamadeh MJ, Liede AC, Thompson LU, Wolever TM, et al. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr. 1994;61:62–68.
    1. Arjmandi BH, Khan DA, Juma S, Drum ML, Venkatesh S, et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutrition Research. 1998;18:1203–1214.
    1. Jenkins DJ, Kendall CW, Vidgen E, Agarwal S, Rao AV, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr. 1999;69:395–402.
    1. Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer pre-surgery: exploring effects on hormonal levels, PSA and histopathology. Urology. 2001;58:47–52.
    1. Lucas EA, Wild RD, Hammond LJ, Khalil DA, Juma S, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab. 2002;87:1527–1532.
    1. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr. 1997;17:353–381.
    1. Prasad K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation. 1999;99:1355–1362.
    1. Prasad K. Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis. 2005;179:269–275.
    1. Hallund J, Ravn-Haren G, Bugel S, Tholstrup T, Tetens I. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women. J Nutr. 2006;136:112–116.
    1. Cunnane SC, Ganguli S, Menard C, Liede AC, Hamadeh MJ, et al. High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans. Br J Nutr. 1993;69:443–453.
    1. Lemay A, Dodin S, Kadri N, Jacques H, Forest JC. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet Gynecol. 2002;100:495–504.
    1. Prasad K. Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG). Mol Cell Biochem. 2000;209:89–96.
    1. Prasad K. Secoisolariciresinol diglucoside from flaxseed delays the development of type 2 diabetes in Zucker rat. J Lab Clin Med. 2001;138:32–39.
    1. Uehar M, Arai Y, Watanabe S, Adlercreutz H. Comparison of plasma and urinary phytoestrogens in Japanese and Finnish women by time-resolved fluoroimmunoassay. Biofactors. 2000;12:217–225.
    1. Johnsson P, Kamal-Eldin A, Lundgren LN, Aman P. HPLC method for analysis of secoisolariciresinol diglucoside in flaxseeds. J Agric Food Chem. 2000;48:5216–5219.
    1. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000;32:S498–S504.
    1. Blake GJ, Pradhan AD, Manson JE, Williams GR, Buring J, et al. Hemoglobin A1c level and future cardiovascular events among women. Arch Intern Med. 2004;164:757–761.
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419.
    1. Nurmi T, Voutilainen S, Nyyssonen K, Adlercreutz H, Salonen JT. Liquid chromatography method for plant and mammalian lignans in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;798:101–110.
    1. Thomas BF, Zeisel SH, Busby MG, Hill JM, Mitchell RA, et al. Quantitative analysis of the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversed-phase high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl. 2001;760:191–205.
    1. Kilpatrick ES. Glycated haemoglobin in the year 2000. J Clin Pathol. 2000;53:335–339.
    1. Jayagopal V, Albertazzi P, Kilpatrick ES, Howarth EM, Jennings PE, et al. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes. Diabetes Care. 2002;25:1709–1714.
    1. Prasad K. Suppression of Phosphoenolpyruvate Carboxykinase Gene Expression by Secoisolariciresinol Diglucoside (SDG), a New Antidiabetic Agent. Int J Angiol. 2002;11:107–109.
    1. Bloedon LT, Szapary PO. Flaxseed and cardiovascular risk. Nutr Rev. 2004;62:18–27.
    1. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999;69:30–42.
    1. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med. 1995;333:276–282.
    1. Zhan S, Ho SC. Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr. 2005;81:397–408.
    1. Gonzalez S, Jayagopal V, Kilpatrick ES, Chapman T, Atkin SL. Effects of isoflavone dietary supplementation on cardiovascular risk factors in type 2 diabetes. Diabetes Care. 2007;30:1871–1873.
    1. Dai Q, Franke AA, Jin F, Shu XO, Hebert JR, et al. Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai. Cancer Epidemiol Biomarkers Prev. 2002;11:815–821.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe