Applied nutritional investigation Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial Sylvie Dodin, M.D. a,b, *, Stephen C. Cunnane, Ph.D. c , Benoît Mâsse, Ph.D. d , André Lemay, M.D. a , Hélène Jacques, Ph.D. b , Geneviève Asselin, M.Sc. a , Jennifer Tremblay-Mercier, M.Sc. c , Isabelle Marc, M.D. a , Benoît Lamarche, Ph.D. b , France Légaré, M.D. a , and Jean-Claude Forest, M.D. a a Departments of Obstetrics and Gynecology, Biochemistry, and Family Medicine, Research Center, St-François d’Assise Hospital (CHUQ), Quebec, Quebec, Canada b Institute of Nutraceuticals and Functional Foods, Laval University, Quebec, Quebec, Canada c Research Center on Aging, CSSS-IUGS, Sherbrooke, Quebec, Canada d Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Manuscript received June 13, 2007; accepted September 26, 2007. Abstract Objective: Due to its high content of lignans, -linolenic acid and fiber, flaxseed may reduce cardiovascular disease risk in humans. The present study evaluated the effect of flaxseed on markers of cardiovascular disease risk in healthy menopausal women. Methods: One hundred ninety-nine women were randomly assigned to consume 40 g daily of flaxseed or wheat germ placebo for 12 mo. Fatty acids, apolipoproteins A-1 and B, lipoprotein(a), low-density lipoprotein particle size, fibrinogen, C-reactive protein, insulin, and glucose were measured at baseline and at 12 mo. Results: In total 179 women were available for the intention-to-treat analysis. Flaxseed increased plasma -linolenic ( P  0.0001), docosapentaenoic ( P = 0.001), and total -3 fatty ( P = 0.0004) acids. Differences between flaxseed and wheat germ were observed for apolipoprotein A-1 (-0.10  0.26 g/L, P = 0.011) and apolipoprotein B (-0.05  0.16 g/L, P = 0.047). From baseline, flaxseed raised apolipopro- teins A-1 and B by 4.4% (P = 0.006) and 3% (P = 0.054), whereas wheat germ increased these apolipoproteins by 11.6% (P  0.0001) and 7% (P = 0.0001), respectively. Both treatments increased lipoprotein(a) (P  0.0001) and decreased low-density lipoprotein peak particle size (P  0.0001). Conclusion: In this large, long-term, placebo-controlled trial in healthy menopausal women, flaxseed increased some -3 fatty acids in plasma and had a limited effect on apolipoprotein metabolism. © 2008 Elsevier Inc. All rights reserved. Keywords: Flaxseed; Cardiovascular disease; -3 Fatty acid; Apolipoprotein; Low-density lipoprotein particle size; Menopause Introduction Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women [1]. Together with tra- ditional risk factors for CVD, including obesity, abnormal plasma lipid profile, hypertension, diabetes, and sedentary lifestyle, an important risk factor in women is hypoestro- genemia after menopause [2,3]. Lifestyle and diet are the firstline interventions to reduce short-term and long-term cardiovascular risk factors [4,5]. The Adult Treatment Panel III recommends consuming diets rich in fibers (20 –30 g/d), 5–10 g of which should be soluble fiber, and low in satu- rated fat (7%) to reduce CVD risk [5]. Due to its high content of lignans, -linolenic acid (LNA) and fiber, flaxseed has a beneficial effect on CVD risk factors [6 –9]. Flaxseed is the richest food source of This study was supported by grants from the Flax Council of Canada, NSERC, and the Canada Research Chairs Secretariat (SCC), the Canadian Institutes of Health Research, and the Heart and Stroke Foundation of Canada. * Corresponding author. Tel.: 418-525-4348; fax: 418-525-4427. E-mail address: sylvie.dodin@ogy.ulaval.ca (S. Dodin). Nutrition 24 (2008) 23–30 www.elsevier.com/locate/nut 0899-9007/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2007.09.003