Flaxseed and Flaxseed Oil in the Management of Hypercholesterolemia
Part I Of A Series On Flaxseed
By Philippe O. Szapary MD, and LeAnne T. Bloedon, MS, RD
The popularity of flaxseed stems from the fact that it contains three important constituents (fiber, alpha linolenic acid, and lignans) that have been implicated in the prevention and treatment of chronic diseases ranging from cardiovascular disease to cancer prevention and inflammatory disorders.
The best evidence to date suggests that flaxseed products improve cardiovascular risk factors primarily by modestly improving lipid profiles. Flaxseed’s anti-arrhythmic, antiplatelet, antioxidant, and hypoglycemic potential will be covered in a separate article.
History
Evidence of flaxseed cultivation can be found as early as 6000 BC in Eastern Turkey, where it was used to make linen.1 During the past millennia, components of flaxseed have been used for a variety of purposes. Traditionally, the oil, known as linseed oil, is used as a drying agent in paint and varnish.
Composition and Pharmacology
Flax (Linum usitatissimum) is a blue flowering crop that produces small, flat seeds that range in color from golden yellow to reddish brown. Flaxseed commonly is found as whole seed, flaxseed powder, or flaxseed oil. Whole flaxseed contains 41% fat, 28% dietary fiber, and 21% protein, in addition to minerals, vitamins, and to a lesser extent, carbohydrates.2
Flaxseed oil is comprised of 73% polyunsaturated fatty acids, 18% monounsaturated fatty acids, and 9% saturated fatty acids, making it a low saturated fat food.2 Flaxseed oil is unique in that it is the richest known source of alpha-linolenic acid (ALA), a compound with cardioprotective effects.3
The dietary fiber portion of flaxseed contains both insoluble and soluble fibers. The lipid-lowering properties of flaxseed fiber are attributed to mucilage, the soluble fiber portion. Although fiber is not digestible by humans, it affects absorption of fat and metabolism of food components by altering transit time.
Flaxseed contains several lignans, which are phyto-estrogens, and is the richest source of the main mammalian lignan precursor, secoisolariciresinol (SDG).4
Mechanism of Action
The fiber portion of flaxseed may lower serum cholesterol by a number of potential mechanisms, including enhanced gastric emptying, altered transit time, interference with bulk-phase diffusion of fat, and increased excretion of bile acids.5
Evidence also suggests that the lignans precursor SDG may directly lower serum cholesterol.6 It has been hypothesized that lignans may be able to lower serum cholesterol through modulation of enzymes involved in cholesterol metabolism, including 7a-hydroxylase and acyl CoA cholesterol transferase.7
| Table 4 |
2.2 g/tbsp
3.3 g/tbsp Yes 59/tbsp $0.99/lb Flaxseed powder 5.4 g/tbsp 3.0 g/tbsp Yes 40/tbsp $5.99/8 ozFlaxseed oil 7.5-10
.5 g/tbsp 0 No 130/tbsp $5.99-8.59/ozLinseed bread
Not listed 5 g (slice) Yes 100/slice $2.99/17.6 oz (The Baker) (8 slices)Flax Plus cereal
600 mg/serving 5 g Yes 120 per ¾ cup $2.99/13.25 ozSources: U.S. Department of Agriculture Nutrient Database for Standard Reference; and online retailers.
Animal Studies
Several animal studies have focused on the question of whether flaxseed, or portions of flax, can improve serum lipids. Weanling rats fed 20% and 40% flaxseed for 90 days produced significantly lower serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than rats fed a diet devoid of flaxseed.8 In rabbits, adding purified SDG (15 mg/kg) to an atherogenic diet for eight weeks reduced TC and LDL-C by 33% and 35%, respectively, while it remarkably increased high-density lipoprotein cholesterol (HDL-C) by more than 140% in as few as four weeks.6
When the authors examined the extent of atherosclerotic burden in the aorta, the SDG-treated group had significantly smaller plaques and the lesions were distributed over a smaller area compared to the control group. The same group of authors found that defatted flaxseed (2-3% ALA, but similar in lignan content to traditional flaxseed) similarly reduced TC and LDL-C in rabbits fed an atherogenic diet for eight weeks when compared to controls, but had no effect on HDL-C.9
Human Studies
To identify the majority of human studies on the lipid effects of flaxseed, we performed a systematic search of the following databases: MEDLINE, BIOSIS Previews, CINHAL, Cochrane Collaboration Database, and CAM on PubMed. We used the MeSH headings "flax," "alpha linolenic acid," "fatty acid, omega-3," "lignans," and "dietary fiber," as well as the search terms "flaxseed" and "linseed." We also hand searched recent relevant review articles for additional references. Using this strategy, we identified 353 articles and book chapters. The description below highlights the information specifically on the lipid-lowering effects of flaxseed products.
The bulk of the evidence from nine clinical trials suggests that flaxseed or flaxseed powder can modestly reduce TC and LDL-C by 5-15%, without an effect on HDL-C or triglycerides (TG).10 Flaxseed oil given alone in large doses (60 mL) can modestly reduce TG.11 One double-blind, randomized controlled trial of 38 moderately hyperlipidemic postmenopausal women (average LDL-C: 158 mg/dL) found that 38 g of whole flaxseed baked into muffins can reduce LDL-C by 14.7% compared to a sunflower seed control muffin.12 There were no effects on TG or HDL-C, but interestingly, lipoprotein (a), a newer marker of coronary heart disease, was mildly but consistently reduced by 7.4%.
In normolipidemic volunteers, Cunnane et al showed that consuming a large amount of ground flaxseed daily (50 g/d in two muffins) reduced LDL-C by 8% at two weeks, and increased bowel movements by 30%.13 These same investigators found similar results using defatted flaxseed muffins in 29 hyperlipidemic subjects over six weeks.14 These results imply that the hypolipidemic effect of flaxseed is independent of ALA content.
We identified six studies that specifically evaluated the lipid effects of flaxseed oil with doses of ALA ranging from 9.2 to 38 g/d. Only the study using the highest dose of ALA, equivalent to 60 mL (about 4 tbsp/d) of flaxseed oil, found a TG-lowering effect of 25%, without changes in TC, LDL-C, or HDL-C.15 This decrease in fasting serum TG is comparable to that obtained with marine fish oil, except that the fish oils produce the TG-lowering effect at much lower doses.
Adverse Effects and Drug Interactions
The Food and Drug Administration allows inclusion of up to 12% (by weight) flaxseed in foods, but flaxseed and cold-pressed flaxseed oil have not attained GRAS (Generally Recognized As Safe) status.
There are no known or suspected adverse effects or interactions with flaxseed oil; however, the fiber and lignan components of flax may cause some problems. Human studies using up to 50 g flaxseed per day for up to one month revealed no adverse effects and that flaxseed was well-tolerated in one study.13 This same study noted a 30% increase in bowel movements with this flaxseed supplementation. Thus, clinicians may want to avoid recommending flaxseed for patients with a history of bowel obstruction, or in some patients with irritable bowel syndrome. Additionally, the small whole seeds could theoretically precipitate a bout of diverticulitis and probably should be avoided by patients with known diverticular disease. Grinding the seeds should remove this theoretical risk.
There is no published evidence concerning the safety of flax in pregnancy or lactation. However, flax has potential hormonal effects, which may result from bioactive lignans binding to estrogen receptors. There are no published reports of drug interactions. Because of their fiber content, flaxseed products probably should not be co-administered with prescription drugs to avoid interference with drug absorption.
Studies looking at another class of phytoestrogens, known as isoflavones, have found that soy isoflavones, genistein and daidzein, cause chromosomal mutations and DNA strand breaks in vitro at high concentrations.2 These genotoxic properties theoretically could increase the risk of neoplasia. Initial studies on lignans from flax reveal no evidence of genotoxicity.16 However, the issue of whether flaxseed or its components may be carcinogenic or chemoprotective actively is being investigated.
Dietary Sources of Flax
Flaxseed is sold in bulk, and in powder and oil forms. The oil is best used in salad dressings and blended into smoothies. The oil also can be used to sauté foods briefly at medium heat; however, it degrades at high temperatures. The oil becomes rancid quickly when exposed to heat, light, and oxygen, and should be stored in an opaque bottle and refrigerated after opening.
Whole flaxseed can be used in a variety of foods when crunchiness or a nutty flavor is desired. In addition to baking whole flaxseed in breads, muffins, pancakes, waffles, or bagels, it can be sprinkled onto cereal, yogurt, or salads. Grinding seeds in a coffee grinder allows the user to mix it into juices or low-fat milk. Whole flaxseed can be stored for up to one year in a dry place. Ground flaxseed can be stored in the refrigerator for approximately three months; when frozen, ground flaxseed can be preserved for six months or longer.
Both flaxseed powder and oil also are sold as dietary supplements. The oil frequently is sold in either capsule form or as a liquid (see Table).
Conclusion
Whole flaxseed and flaxseed powder can modestly reduce LDL-C by 5-10% without affecting HDL-C or TG. Conversely, flaxseed oil does not reliably lower LDL-C, but can reduce TG at high doses. The large amount of flaxseed oil (4 tbsp and 480 calories) needed to reduce TG makes this oil an impractical and highly caloric intervention.
Recommendation
Based on current literature, flaxseed or flaxseed powder can be a useful part of a cholesterol-lowering diet, such as the Therapeutic Lifestyle Changes (TLC) diet, which recently was endorsed by the National Cholesterol Education Program.17 Like psyllium, adding 2 tbsp/d of flaxseed to a diet low in saturated and trans-fatty acids equally will reduce serum cholesterol; unlike psyllium, however, this dose of flax also will add cardioprotective omega-3 fatty acids, making this grain a very useful part of a heart healthy diet.
Dr. Szapary is Assistant Professor in the Division of General Internal Medicine and in the Cardiovascular Risk Intervention Program; Ms. Bloeden is Project Manager in the Cardiovascular Risk Intervention Program, University of Pennsylvania Health System, in Philadelphia.
References
1. Judd A. Flax—some historical perspective. In: Cunnane SC, Thompson LU, eds. Flaxseed in Human Nutrition. Toronto, CA: American Oil Chemists Society Press; 1995:1-10.
2. Morris D. Essential nutrients and other functional compounds in flaxseed. Nutrition Today 2001;36: 159-162.
3. Cunnane SC, et al. High alpha-linolenic acid flaxseed (Linum usitatissimum): Some nutritional properties in humans. Br J Nutr 1993;69:443-453.
4. Thompson LU, et al. Mammalian lignan production from various foods. Nutr Cancer 1991;16:43-52.
5. Kritchevsky D. Fiber effects of hyperlipidemia. In: Cunnane SC, Thompson LU, eds. Flaxseed in Human Nutrition. Toronto, CA: American Oil Chemists Society Press; 1995:174-186.
6. Prasad K. Reduction of serum cholesterol and hyper- cholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation 1999;99:1355-1362.
7. Sanghvi A, et al. Inhibition of rat liver cholesterol 7-alpha hydroxylase and acetyl CoA:cholesterol aceyl transferase activities by entrodiol and enterolactone. In: Kritchevsky D, ed. Proceedings of the Symposium on Drugs Affecting Lipid Metabolism. New York: Plenum Press; 1984:311-322.
8. Ratnayake WMN, et al. Chemical and nutritional studies of flaxseed (variety Linott) in rats. J Nutr Biochem 1992;3:232-240.
9. Prasad K, et al. Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis 1998;136:367-375.
10. Nelson GJ, Chamberlain JG. The effect of dietary alpha-linolenic acid on blood lipids and lipoproteins in humans. In: Cunnane SC, Thompson LU, eds. Flaxseed in Human Nutrition. Toronto, CA: American Oil Chemists Society Press; 1995:187-206.
11. Harris WS. n-3 fatty acids and serum lipoproteins: Human studies. Am J Clin Nutr 1997;65(5 Suppl): 1645S-1654S.
12. Arjmandi BH, et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutr Res 1998; 18:1203-1214.
13. Cunnane SC, et al. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 1995;61:62-68.
14. Jenkins DJ, 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.
15. Singer P, et al. A possible contribution of decrease in free fatty acids to low serum triglyceride levels after diets supplemented with n-6 and n-3 polyunsaturated fatty acids. Atherosclerosis 1990;83:167-175.
16. Kulling SE, et al. Studies on the genotoxicity of the mammalian lignans enterolactone and enterodiol and their metabolic precursors at various endpoints in vitro. Mutat Res 1998;416:115-124.
17. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
Szapary PO, Bloedon LT. Flaxseed and flaxseed oil in the management of hypercholesterolemia. Part 1. Altern Med Alert 2001;12:140-143.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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