Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease

Journal of Nutrition

Volumn 145, Issue 4, 2015, Pages 749-757

  Edel, Andrea L ^a   Rodriguez Leyva, Delfin ^b   Maddaford, Thane G ^a   Caligiuri, Stephanie P B ^a   Alejandro Austria, J ^a   Weighell, Wendy ^a   Guzman, Randolph ^a   Aliani, Michel ^a   Pierce, Grant N ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

^b Cardiovascular Research Division   (Cuba)

Author keywords

Cholesterol lowering; Flaxseed; Peripheral artery disease; Platelet aggregation; Statins

Indexed keywords

ATORVASTATIN; BEZAFIBRATE; CHOLESTEROL; COLESTYRAMINE; EZETIMIBE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; HYPOCHOLESTEROLEMIC AGENT; PLANT MEDICINAL PRODUCT; TRIACYLGLYCEROL;

ARTICLE; CARDIOVASCULAR EFFECT; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DIET SUPPLEMENTATION; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; HUMAN; HYPERLIPIDEMIA; LINSEED; LIPID BLOOD LEVEL; LOW DRUG DOSE; MAJOR CLINICAL STUDY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; RANDOMIZED CONTROLLED TRIAL; THROMBOCYTE AGGREGATION; ADULT; BIOASSAY; BLOOD; CHEMISTRY; DIET; DRUG EFFECTS; FEMALE; FLAX; MALE; PERIPHERAL ARTERIAL DISEASE; PHYTOTHERAPY; PLANT SEED;

TRITICUM AESTIVUM;

ADULT; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL, HDL; CHOLESTEROL, LDL; DIET; DOUBLE-BLIND METHOD; ENDPOINT DETERMINATION; FEMALE; FLAX; HUMANS; MALE; PERIPHERAL ARTERIAL DISEASE; PHYTOTHERAPY; PLANT PREPARATIONS; PLATELET AGGREGATION; SEEDS; TRIGLYCERIDES;

EID: 84928529226     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.114.204594     Document Type: Article

References (52)

1. Dupasquier CM, Weber AM, Ander BP, Rampersad PP, Steigerwald S, Wigle JT, Mitchell RW, Kroeger EA, Gilchrist JS, Moghadasian MM, et al. Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits. Am J Physiol Heart Circ Physiol 2006;291:H2987-96.
2. Dupasquier CM, Dibrov E, Kneesh AL, Cheung PK, Lee KG, Alexander HK, Yeganeh BK, Moghadasian MH, Pierce GN. Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions. Am J Physiol Heart Circ Physiol 2007;293:H2394-402.
3. Francis AA, Deniset JF, Austria JA, LaVallee RK, Maddaford GG, Hedley TE, Dibrov E, Pierce GN. The effects of dietary flaxseed on atherosclerotic plaque regression. Am J Physiol Heart Circ Physiol 2013;304:H1743-51.
4. Ander BP, Weber AR, Rampersad PP, Gilchrist JS, Pierce GN, Lukas A. Dietary flaxseed protects against ventricular fibrillation induced by ischemia-reperfusion in normal and hypercholesterolemic rabbits. J Nutr 2004;134:3250-6.
5. Cunnane SC, Hamadeh MJ, Liede AC, Thompson LU, Wolever TM, Jenkins DJ. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 1995;61:62-8.
6. Dew TP, Williamson G. Controlled flax interventions for the improvement of menopausal symptoms and postmenopausal bone health: a systematic review. Menopause 2013;20:1207-15.
7. Taylor CG, Noto AD, Stringer DM, Froese S, Malcolmson L. Dietary milled flaxseed and flaxseed oil improve n-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type 2 diabetes. J Am Coll Nutr 2010;29:72-80.
8. Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97.
9. Leyva DR, Zahradka P, Ramjiawan B, Guzman R, Aliani M, Pierce GN. The effect of dietary flaxseed on improving symptoms of cardiovascular disease in patients with peripheral artery disease: rationale and design of the FLAX-PAD randomized controlled trial. Contemp Clin Trials 2011;32:724-30.
10. Rodriguez-Leyva D, Weighell W, Edel AL, LaVallee R, Dibrov E, Pinneker R, Maddaford TG, Ramjiawan B, Aliani M, Guzman R, et al. Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hypertension 2013;62:1081-9.
11. Kaul N, Kreml R, Austria JA, Richard MN, Edel AL, Dibrov E, Hirono S, Zettler ME, Pierce GN. A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr 2008;27:51-8.
12. Khalatbari Soltani S, Jamaluddin R, Tabibi H, Mohd Yusof BN, Atabak S, Loh S-P, Rahmani L. Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities. Hemodial Int 2013;17:275-81.
13. Jáuregui-Garrido B, Jáuregui-Lobera I. Interactions between antiarrhythmic drugs and food. Nutr Hosp 2012;27:1399-407.
14. Badimon L, Vilahur G, Padro T. Nutraceuticals and atherosclerosis:human trials. Cardiovasc Ther 2010;28:202-15.
15. Gao LG, Cao J, Mao Q-x, Lu X-c, Zhou X-l, Fan L. Influence of omega-3 polyunsaturated fatty acid-supplementation on platelet aggregation in humans: a meta-analysis of randomized controlled trials. Atherosclerosis 2013;226:328-34.
16. Bainton D, Sweetnam P, Baker I, Elwood P. Peripheral vascular disease:consequence for survival and association with risk factors in the Speedwell Prospective Heart Disease Study. Br Heart J 1994;72:128-32.
17. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-24.
18. Diehm C, Schuster A, Allenberg JR, Darius H, Haberl R, Lange S, Pittrow D, von Stritzky B, Tepohl G, Trampisch HJ. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis 2004;172:95-105.
19. Caligiuri SPB, Aukema HM, Ravandi A, Guzman R, Dibrov E, Pierce GN. Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an alpha-linolenic acid-induced inhibition of soluble epoxide hydrolase. Hypertension 2014;64:53-9.
20. Dodin S, Lemay A, Jacques H, Légaré F, Forest JC, Mâsse B. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab 2005;90:1390-7.
21. Aliani M, Ryland D, Pierce GN. Effect of flax addition on the flavor profile of muffins and snack bars. Food Res Int 2011;44:2489-96.
22. Aliani M, Ryland D, Pierce GN. Effect of flax addition on the flavor profile and acceptability of bagels. J Food Sci 2012;77:S62-70.
23. Edel AL, Aliani M, Pierce GN. Supported liquid extraction in the quantitation of plasma enterolignans using isotope dilution GC/MS with application to flaxseed consumption in healthy adults. J Chromatogr B Analyt Technol Biomed Life Sci 2013;912:24-32.
24. Austria JA, Richard MN, Chahine MN, Edel AL, Malcolmson LJ, Dupasquier CM, Pierce GN. Bioavailability of alpha-linolenic acid in subjects after ingestion of three different forms of flaxseed. J Am Coll Nutr 2008;27:214-21.
25. Khawaja FJ, Kullo IJ. Novel markers of peripheral arterial disease. Vasc Med 2009;14:381-92.
26. Bloedon LT, Balikai S, Chittams J, Cunnane SC, Berlin JA, Rader DJ, Szapary PO. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr 2008;27:65-74.
27. Arjmandi BH, Khan DA, Juma S, Drum ML, Venkatesh S, Sohn E, Wei L, Derman R. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutr Res 1998;18:1203-14.
28. Patade A, Devareddy L, Lucas EA, Korlagunta K, Daggy BP, Arjmandi BH. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. J Womens Health (Larchmt) 2008;17:355-66.
29. Mandas'escu S, Mocanu V, Dascalita AM, Haliga R, Nestian I, Stitt PA, Luca V. Flaxseed supplementation in hyperlipidemic patients. Rev Med Chir Soc Med Nat Iasi 2005;109:502-6.
30. Jenkins DJ, Kendall CW, Vidgen E, Agarwal S, Rao AV, Rosenberg RS, Diamandis EP, Novokmet R, Mehling CC, Perera T, 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.
31. Cunnane SC, Ganguli S, Menard C, Liede AC, Hamadeh MJ, Chen ZY, Wolever TM, Jenkins DJ. High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans. Br J Nutr 1993; 69:443-53.
32. Dodin S, Cunnane SC, Mâsse B, Lemay A, Jacques H, Asselin G, Tremblay-Mercier J, Marc I, Lamarche B, Légaré F, et al. Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial. Nutrition 2008;24:23-30.
33. Patenaude A, Rodriguez-Leyva D, Edel AL, Dibrov E, Dupasquier CM, Austria JA, Richard MN, Chahine MN, Malcolmson LJ, Pierce GN. Bioavailability of alpha-linolenic acid from flaxseed diets as a function of the age of the subject. Eur J Clin Nutr 2009; 63:1123-9.
34. Bureau of Nutritional Sciences Food Directorate, Health Products and Food Branch [Internet]. Summary of Health Canada's assessment of a health claim about ground whole flaxseed and blood cholesterol lowering. Ontario (Canada): Bureau of Nutritional Sciences; 2014 [cited 2014 Sep 19]. Available from: http://www.hc-sc.gc.ca/fn-an/alt_formats/pdf/label-etiquet/claims-reclam/assess-evalu/flaxseed-graines-de-lin-eng.pdf.
35. Lucas EA, Wild RD, Hammond LJ, Khalil DA, Juma S, Daggy BP, Stoecker BJ, Arjmandi BH. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab 2002;87:1527-32.
36. Adlercreutz H. Lignans and human health. Crit Rev Clin Lab Sci 2007;44:483-525.
37. Wong H, Chahal N, Manlhiot C, Niedra E, McCrindle BW. Flaxseed in pediatric hyperlipidemia: a placebo-controlled, blinded, randomized clinical trial of dietary flaxseed supplementation for children and adolescents with hypercholesterolemia. JAMA Pediatr 2013;167:708-13.
38. Stuglin C, Prasad K. Effect of flaxseed consumption on blood pressure, serum lipids, hemopoietic system and liver and kidney enzymes in healthy humans. J Cardiovasc Pharmacol Ther 2005;10:23-7.
39. Sharma S, Thapa R, Jeevanantham V, Myers T, Hu C, Brimacombe M, Vacek JL, Dawn B, Gupta K. Comparison of lipid management in patients with coronary versus peripheral arterial disease. Am J Cardiol 2014;113:1320-5.
40. Faintuch J, Horie L, Barbeiro H, Barbeiro D, Soriano F, Ishida R, Cecconello I. Systemic inflammation in morbidly obese subjects:response to oral supplementation with alpha-linolenic acid. Obes Surg 2007;17:341-7.
41. Harper CR, Edwards MC, Jacobson TA. Flaxseed oil supplementation does not affect plasma lipoprotein concentration or particle size in human subjects. J Nutr 2006;136:2844-8.
42. Almario RU, Karakas SE. Lignan content of the flaxseed influences its biological effects in healthy men and women. J Am Coll Nutr 2013;32:194-9.
43. Fukumitsu S, Aida K, Shimizu H, Toyoda K. Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men. Nutr Res 2010;30:441-6.
44. 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.
45. Staudt Dumas MA. Clinical snapshot. Intermittent claudication. Am J Nurs 1995;95:34-5.
46. Gajos G, Zalewski J, Rostoff P, Nessler J, Piwowarska W, Undas A. Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI Clot). Arterioscler Thromb Vasc Biol 2011;31:1696-702.
47. Gajos G, Rostoff P, Undas A, PiwowarskaW. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGAPCI (OMEGA-3 fatty acids after PCI to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol 2010;55:1671-8.
48. Holy EW, Forestier M, Richter EK, Akhmedov A, Leiber F, Camici GG, Mocharla P, Lüscher TF, Beer JH, Tanner FC. Dietary a-linolenic acid inhibits arterial thrombus formation, tissue factor expression, and platelet activation. Arterioscler Thromb Vasc Biol 2011;31:1772-80.
49. Lev EI, Solodky A, Harel N, Mager A, Brosh D, Assali A, Roller M, Battler A, Kleiman NS, Kornowski R. Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll Cardiol 2010;55:114-21.
50. Kauskot A, Hoylaerts M. Antiplatelet agents: platelet receptors. Gresele P, Born GVR, Patrono C, Page CP, editors. Berlin, Heidelberg: Springer-Verlag; 2012. p. 23-57.
51. Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251:365-74.
52. Egan BM, Li J, Qanungo S, Wolfman TE. Blood pressure and cholesterol control in hypertensive hypercholesterolemic patients: National Health and Nutrition Examination Surveys 1988-2010. Circulation 2013;128:29-41.