Flax is making its mark in the world’s food supply as a functional food. Functional foods deliver a health boost beyond what might be expected from their traditional nutrient content (1,2). Flax fits this description perfectly, being rich in alpha-linolenic acid (ALA), the essential omega-3 fatty acid, and phytochemicals, while also providing dietary fiber and protein.

There are two essential fatty acids (EFAs) in human nutrition: alpha-linolenic acid (ALA), an omega-3 fatty acid, and linoleic acid (LA), an omega-6 fatty acid. Humans must obtain EFAs from foods because the human body cannot make them. EFAs are required for the structure of cell membranes and, because they are unsaturated, they help keep membranes flexible. They serve as precursors of eicosanoids, a group of powerful compounds that affect many biological processes, including the aggregation or clumping of blood platelets and the constriction of blood vessels. EFAs also help maintain the barrier of the skin and are involved in cholesterol metabolism (31).

ALA has three main biologic effects, which together contribute to its positive health effects.

1. ALA functions as the precursor of EPA and DHA. Its effect on blood clot formation may differ from those of EPA and DHA (64,65), and its presence in colostrum and breast milk suggests a role for ALA in the growth and development of infants (66,67). ALA appears to play a role in maintaining the health of skin and fur in mammals (68).

2. ALA-rich diets increase the ALA, EPA and total omega-3 fatty acid content of cell membrane phospholipids. For example, the serum level of ALA increased 12%, EPA increased 11% and DPA (docosapentaenoic acid) increased 5% when 80 volunteers ate meals enriched with ground flax and flax oil for four weeks (69). Increasing the omega-3 fatty acid content of membrane phospholipids increases the flexibility of membranes and alters the way they behave in beneficial ways (70).

3. ALA dampens inflammatory reactions by blocking the formation of compounds that promote inflammation. Inflammation is a feature of many chronic diseases, including atherosclerosis or "hardening of the arteries," the underlying condition that contributes to heart attacks and strokes.

Cardiovascular disease (CVD) includes all diseases of the blood vessels and heart, such as coronary heart disease (CHD) and stroke. CVD is the leading cause of death in Canada and the United States (70). This chapter reviews the evidence that flax and one of its key nutrients, alpha-linolenic acid (ALA), offer protection against CVD.

CVD is the result of atherosclerosis, an inflammatory disease that can begin in childhood (61). As atherosclerosis develops, deposits of cholesterol and other blood lipids accumulate in blood vessel walls. This process is governed by oxidized low-density lipoprotein (LDL), eicosanoids, cytokines and other blood factors. Eventually, plaques form and harden in the blood vessel wall. Plaques can grow large enough to restrict blood flow to the heart and brain. Blood flow can also be impeded by a clot or thrombus. Thrombosis is the sudden formation of a clot initiated by the clumping (aggregation) of blood platelets. When a clot forms in the heart and blocks blood flow, it causes a myocardial infarction or heart attack. When a clot blocks blood flow in the brain, it causes a stroke. Dietary fatty acids appear to be involved in both processes, although their effect on atherosclerosis is better defined than it is in thrombosis (137).

Blood clots formed in the heart cause ischemia, meaning the blood flow through the heart muscle is blocked. Ischemia is the most common trigger of arrhythmias (138). In dogs, intravenous infusion of pure ALA was as effective as pure eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in protecting the animals against arrhythmias (139). In test tube studies of heart cells taken from rats, the effects of ALA, EPA and DHA were similar in preventing arrhythmias (140). The omega-3 fatty acids are believed to protect against arrhythmia by first being released from membrane phospholipids and then changing the physical state of the membrane in such a way that it becomes less excitable (138). Whether these effects occur in humans is not clear. One study found no effect of EPA and DHA in fish oil on the electrophysiology of the heart in healthy men and women (141). However, there is evidence from clinical, prevention and epidemiologic studies that sudden cardiac death, which is usually the result of ischemia-induced arrhythmia, is lower in people who eat diets high in ALA.

Dietary interventions to reduce CHD risk focus mainly on decreasing the intake of saturated and trans fatty acids to lower blood cholesterol. Trans fatty acids are formed when vegetable oils are processed to make them more stable or solid (142). Trans fatty acids behave somewhat like saturated fat in that they can raise blood LDL cholesterol. Reducing the intake of saturated fat and trans fatty acids and increasing the intake of polyunsaturated fat, monounsaturated fat and dietary fiber help lower blood total cholesterol and LDL cholesterol (143). Diets rich in ALA, found abundantly in flax, appear to offer protection against sudden cardiac death and stroke. The cardioprotective effects of ALA and flax are described in this section.

Eating 2–6 tbsp of ground flax daily for as little as four weeks reduced blood total and LDL cholesterol significantly in clinical trials. Blood total cholesterol decreased 6– 9% and LDL cholesterol decreased 9–18% in studies of healthy young adults (40,55), men and women with moderately high levels of blood cholesterol (144) and postmenopausal women (145) who ate ground flax. High-density lipoprotein (HDL) cholesterol and triglyceride levels were not affected by diets containing ground flax.

The effect of ground flax on blood lipids was confounded in these studies by the fiber content of flax. Indeed, Jenkins and colleagues proposed that the mucilage gums are most likely responsible for the lipid-lowering effects of flax (146). In their study, 29 men and women with high blood cholesterol levels ate muffins made with wheat bran or muffins made with partially defatted flax for three weeks. The subjects ate four muffins daily. The four flax muffins provided 50 g of partially defatted flax all together. Partially defatted flax contains less than 10% fat by weight, whereas regular flax contains about 41% fat. The subjects’ total cholesterol decreased about 5% and LDL cholesterol decreased 8% on the partially defatted flax diet. The study findings suggest a role for flax mucilage gums in lowering blood lipids, but the contribution of ALA to the study findings cannot be ignored – the four flax muffins eaten daily provided a significant amount of ALA (3.5 g/day). In this case, the study design did not allow the researchers to completely separate the effects of the mucilage gums from those of ALA.  Whereas ground flax helps lower blood lipids, clinical studies show no effect of flax seed oil consumption on blood total cholesterol, LDL cholesterol and triglycerides (37–39,147–150). HDL cholesterol was unchanged in five of these studies (37–39,148,149) but decreased 9% in two studies (147,150).  At first glance, it appears that the fiber content of flax is more important than the ALA content in reducing CHD risk, especially if one looks only at the effects of flax oil on blood cholesterol. However, ALA has been reported to decrease blood cholesterol levels in animals and humans. In rats, feeding an ALA-rich diet lowered cholesterol levels (151) and reduced the number of arrhythmias and deaths (152,153). In humans, ALA obtained from a mixture of vegetable oils, including flax oil, was equally effective as oleic acid and linoleic acid in lowering total cholesterol by 18% and LDL cholesterol by 22% (154). So, ground flax and flax seed oil may both favorably improve CHD risk. The fiber in ground flax may work cooperatively with ALA in lowering blood cholesterol. In ALA-rich flax oil, which contains no fiber, the cardioprotective effects of ALA may have less to do with lowering blood cholesterol and more to do with other important actions of ALA that reduce CHD risk. For instance, ALA helps limit inflammatory reactions that contribute to atherosclerosis.

The Lyon Diet Heart Study was a prevention trial designed to reduce the risk of CVD deaths in survivors of a heart attack (65). The key finding of this study was that the 302 men and women who ate a Mediterranean type diet rich in ALA had a 70% reduction in their risk of heart attack compared with the 303 men and women in the control group who ate a prudent diet that resembled the American Heart Association diet. This result was achieved without a reduction in blood cholesterol. In a follow-up at 46 months, ALA continued to be the key fatty acid whose presence in the diet was associated with a good prognosis for preventing a second, fatal heart attack. Dietary intakes of the long-chain omega-3 fatty acids (EPA and DHA) found mainly in fatty fish like salmon and mackerel were not as important as ALA in this study (155).  The Multiple Risk Factor Intervention Trial (MRFIT) showed that the higher the ALA intake, the lower the risk of death from CVD, CHD and all causes of death combined (156). MRFIT was a study of more than 12,000 men aged 35–57 years who were followed for six to eight years.

Epidemiologic studies are concerned with determining how many people in the community have a certain disease and identifying the risk factors associated with its development. Measurements are made on hundreds, sometimes thousands, of individuals, and then the data are examined for trends and links between diet or lifestyle and the presence of disease. Several epidemiologic studies suggest that diets rich in ALA reduce CVD risk (157–159). For example, the Health Professionals Follow-up Study, which began in 1986 with a group of more than 51,000 middleaged and elderly men, found a specific preventive effect of ALA. Those men with the highest ALA intakes had the lowest risk of heart attack and fatal heart disease. The effect of ALA was independent of other dietary and non-dietary risk factors. Intake of marine omega-3 fatty acids (EPA and DHA) was not associated with heart attack risk in this study population, suggesting that the cardiovascular effects of ALA are different from those of EPA and DHA (64). Other large-scale population studies such as the Family Heart Study (158) and the Nurses’ Health Study (159) found the risk of having a fatal heart attack and CHD decreased as the intake of ALA increased. The ALA intakes in the studies ranged from 0.9 to 1.8 g/d. One study did not find a beneficial effect of ALA on CVD risk (160). The Zutphen Elderly Study of 667 men aged 64–84 years found a small, non-significant association between ALA intake and CVD risk, due mainly to the fact that the men’s ALA intake was obtained chiefly from foods like margarine, meat and bread that contain trans fatty acids. ALA intake from foods without trans fatty acids was not associated with CVD risk. The increased risk of CVD seen with high ALA intakes in this study may be due to trans fatty acids or other nutrients in the diet (161). Taken all together, a majority of large-scale population studies show that people who consume ALA-rich diets have a lower risk of CVD (refer to Table 11). A cardioprotective effect of ALA was seen in these studies despite differences in study populations, length of follow-up, outcomes and method of analyzing the study data statistically. A consensus is emerging that ALA has beneficial effects in the prevention of CVD (162,163).

A small group of men who participated in the Multiple Risk Factor Intervention Trial (MRFIT) were examined separately for risk of stroke.  Among the 96 men, each increase of 0.06% in the ALA content of serum phospholipids was associated with a 28% decrease in risk of stroke (164). After controlling for risk factors of stroke like smoking and blood pressure, ALA emerged as an independent predictor of stroke risk – that is, men with higher levels of ALA in their serum phospholipids had a lower stroke risk.

Two flax components – its ALA and lignans – may protect against CVD through their actions on inflammatory reactions, lipoproteins and blood vessels. Some potential mechanisms include the following:

1. ALA blocks the production of pro-inflammatory eicosanoids. (Refer to Chapter 2 for information about eicosanoids.) For example, the concentration of thromboxane B2 decreased 30% in immune cells of 28 healthy men who consumed 13/4 tbsp of flax seed oil daily for four weeks (74).