Nutraceuticals

(5) Flaxseed and flaxseed oil

By Lisa Rapport, BPharm, MRPharmS, and Brian Lockwood, PhD, MRPharmS

Flaxseed is a good source of alpha-linolenic acid, which is converted to long-chain omega-3 fatty acids. Like fish oils it may help to correct deficiency of these fatty acids and could be useful for those wishing to supplement their diets with a plant source of these nutrients

Flax (Linum usitatissimum) has been used traditionally for its fibre, which was woven to make cloth, and its seeds, also known as linseed, which provided oil for food and paint.¹ Early writings also describe the use of both seeds and oil to treat different medical conditions.² Over the past 10 years or so, flaxseed has been rediscovered and its potential health benefits are again being investigated.

Many animal and human studies have looked at the role of flaxseed in prevention and treatment of disease, including heart disease, hypertension, inflammatory and autoimmune disease and cancer.

Chemistry

Flaxseed contains more than 50 per cent a-linolenic acid (ALA), one of the two essential fatty acids required by humans, which cannot be made by the body and must be ingested. In ALA there are 18 carbon atoms with three unsaturated bonds, starting at the third carbon atom, which is described by the notation 18:3w3, and ALA is sometimes referred to as an omega-3 (or n-3) polyunsaturated fatty acid (PUFA).^1,3 The other essential fatty acid is linoleic acid, which is an omega-6 or n-6 fatty acid.

The modern, western diet contains a much greater quantity of omega-6 than omega-3 fatty acids, in a ratio of 20–30 to one, although ideally the ratio should be almost equal. Recommendations to replace saturated with unsaturated fatty acids, to improve coronary health, have contributed to this imbalance. Moreover, because of modern industrial and agricultural practice, the omega-3 content of many foods, including meat, fish, eggs and vegetables, is much lower than before. As a result many people are deficient in omega-3 ALA, which may lead to degenerative disease.

Both omega-6 and omega-3 fatty acids are precursors of eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Those eicosanoids derived from omega-6 fatty acids have opposing properties to those derived from omega-3s and it is therefore important to have a balance between the two. A diet rich in omega-6s and lacking in omega-3s tends to lead to thrombi, blood aggregation and cardiovascular disease, as well as allergies, inflammation and diabetes.

Fish oils have long been recognised as a source of long chain omega-3 PUFAs and much research has been carried out investigating these oils. However, flaxseed is the richest plant source of the precursor ALA, which is converted to these long chain fatty acids and it therefore provides another way to correct deficiency and prevent diseases associated with decreased omega-3 fatty acids.

Only recently have the benefits of flaxseed as a source of these essential fatty acids been realised. Long chain omega-3 fatty acid production from ALA depends on how much omega-6 fatty acid is already present, and proceeds less efficiently when there is an excess of omega-6s. The production of these long chain fatty acids from ALA is therefore more significant over a long period, as most people have a vast excess of omega-6s. One advantage of ALA over fish oils is that the problem of inadequate vitamin E intake does not occur when plant sources are used.³ In addition, as well as being a precursor for longer chain omega-3 fatty acids, ALA has clinically relevant effects in its own right, which offers another benefit over omega-3 containing fish oils.⁴

The optimum amount of ALA is thought to be provided by about one or two teaspoons of the oil daily (2–9g).¹ While still in the seed, the oil will keep for years, but once extracted it should be carefully stored and dated with a shelf life as it is sensitive to heat and light. Freezing is an alternative way of ensuring that the oil is in prime condition while being stored. In addition, plant oils are often hydrogenated during processing, and this destroys the ALA found in the pure oil. It is therefore important to ensure that flaxseed oil purchased for its therapeutic properties is not in this form.⁴

Oil or seed?

In a crossover study,² 12g ALA daily as flaxseed oil capsules (taken three times a day) were compared with flaxseed flour (added to foods) in a group of healthy young women. The bioavailability of the ALA was similar in each case and resulted in lowered blood lipids. In addition, although flaxseed is a high calorie food providing 280kcal/50g, over the four-week period, there was no weight gain in the subjects, indicating that other energy sources had been displaced from the diet.

In another experiment by the same team of researchers, flaxseed flour sprinkled on foods was compared with bread made from the flour, both providing 50g/day of flaxseed for four weeks. Fatty acid profiles did not differ significantly between the two groups with the effect being mainly on the low density lipoprotein cholesterol (LDL-C) and again no weight gain was reported. It appears that the form in which flaxseed is consumed, whether flour, oil or in baked goods, does not affect the bioavailability of the ALA.

Cardiovascular disease

The eicosanoids originating from arachidonic acid, which are produced from omega-6 fatty acids, are hyperlipidaemic, prothrombotic and pro-aggregatory and can lead to atherosclerotic disease if present in too high a concentration. However, the eicosanoids derived from omega-3s have the opposite effects.³ Flaxseed would therefore seem to be a good supplement for lowering cholesterol and improving heart function.

In a large trial (n=584) carried out in 1994, the effect of an ALA-rich diet was compared with a normal diet in survivors of a first myocardial infarction.⁵ The experimental diet included a high intake of ALA, and also fruits and vegetables, which are high in antioxidants. A reduction in coronary events and cardiac deaths of close to 70 per cent was seen in the experimental group over five years. The high intake of antioxidants may well have increased the positive effects of the experimental diet but an increase in ALA seems to have significant consequences for coronary health.

Aortic compliance (or elasticity) is related to arterial function and a decrease leads to an increased risk of coronary heart disease. Supplementation with 20g flaxseed oil daily improved aortic compliance over a four-week period in obese subjects.⁶ This finding may have relevance for elderly, diabetic or obese patients, all of whom show a tendency to reduced aortic elasticity.

In a small trial, healthy, young, non-smoking males (n=11) took 40g flaxseed oil or sunflower seed oil (which is a source of omega-6 linoleic acid) daily for 23 days, in addition to their low-fat diet.⁷ Omega-6: omega-3 ratios varied from 1:2 in the flaxseed group to 30:1 in the sunflower group. The platelet content of eicosapentaenoic acid (EPA), a long chain fatty acid produced by chain elongation of ALA, which is associated with decreased collagen induced platelet aggregation and thrombosis, more than doubled in the study time. However, no conclusions were reached as to the optimal ratios of omega-6:omega-3 in the diet or to the exact mechanism of action of decreased aggregation.

Conflicting results have been reported with the effect of flaxseed oil on serum cholesterol. In one small, crossover experiment using healthy young adults, consumption of two muffins without flaxseed acted as the control and consumption of two muffins containing 25g flaxseed each acted as the intervention. The muffins were consumed daily for four weeks.⁸ After two weeks of flaxseed muffin consumption, total cholesterol and LDL-C had decreased significantly by 6 and 9 per cent, respectively, a reduction that was maintained throughout the four weeks of the study. But by week four, total and LDL-C were similar in the two groups. However, plasma high density lipoprotein cholesterol (HDL-C) was unchanged in both groups.

Evaluation of many human studies⁹ led the authors of a review to the conclusion that ALA is equivalent to omega-6 oils but not as powerful as omega-3 fish oils in its effects on lowering serum cholesterol, unless the ALA is ingested in very large quantities. In another study,¹⁰ the effect of low dose flaxseed or fish oils in subjects consuming diets with a high (n=11) or low (n=15) polyunsaturated/saturated fatty acid diet was investigated. In contrast to fish oil, flaxseed oil did not reduce triacylglycerides in either group, but this could have been due to the small dose (35mg/kg/day).

In rabbits, flaxseed was shown to reduce hypercholesterolaemic atherosclerosis by 46 per cent,¹¹ although total serum cholesterol and LDL-cholesterol were increased. This led the researchers to consider whether the anti-atherosclerotic properties of flaxseed were possibly due to the lignan content of the flaxseed rather than ALA. So, they used another type of flaxseed which has only 2–3 per cent of its oil as ALA but with a similar lignan content, and rabbits were again used to determine the effect of this type of flaxseed on atherosclerosis.¹² The development of atherosclerosis was reduced by 69 per cent without significant changes in serum lipids. This seems to indicate that other constituents of flaxseed, rather than ALA alone, are indeed responsible for the effects seen. Similarly, in an experiment with humans,¹³ 29 hyperlipidaemic subjects were given partially defatted flaxseed baked into muffins, and reductions in serum LDL-cholesterol were similar to those given full fat flaxseed, although there was no effect on serum lipoprotein.

The papers reviewed strongly suggest that flaxseed could be a beneficial supplement in the prevention of cardiovascular events, including heart attacks and strokes induced by hypercholesterolaemia. For this use it would seem that whole flaxseed is superior to the purified oil, although the exact mechanism has yet to be confirmed.

Blood glucose

In the standard blood glucose test, blood is tested at intervals following ingestion of the test substance after an overnight fast. Bread made from flaxseed flour was compared with white bread, and flaxseed mucilage mixed with glucose was compared with glucose alone, in one such blood glucose determination.² Post-prandial blood glucose was reduced by about 27 per cent in each group given flaxseed. In a similar experiment comparing glucose tolerance after consuming flaxseed muffins or white flour muffins for four weeks,⁸ the 30-minute blood glucose concentration was significantly lower in the flaxseed group. These results indicate a possible use for the incorporation of flaxseed into foods and snack products aimed at the diabetic population.

Immune status

Conflicting results as to the effect of dietary fats on the immune system in animal models have been reported.¹⁴ A small crossover study was carried out to determine the effect of ALA on the immune status of 10 healthy, young men over a period of 126 days. For half the study period, five participants received a normal diet and the other five received a diet supplemented with flaxseed oil, and then the groups were crossed over. Blood samples were drawn at intervals throughout the two periods. The supplemented diet suppressed the immunity from T-cells (cell-mediated immunity) but not from B-cells (humoral immunity). These findings may have been due to the increased amount of fat in the diet as well as the ALA supplement.

More work is necessary in this area to determine if effects on the immune system are a real threat to flaxseed users. Immunosuppression could be a health risk if experienced over long periods, but it could also be beneficial for patients with autoimmune diseases, such as arthritis.

A small study in eight patients with the autoimmune disease systemic lupus erythematosus was carried out.¹⁵ The lupus was present in these patients as lupus nephritis, affecting the kidney. Flaxseed at a dose of up to 30g/day was found to improve renal function and inflammatory mechanisms and it was well tolerated.

Another trial,¹⁶ using 30g flaxseed oil for three months in a small number of patients with rheumatoid arthritis, found no improvement in the experimental group compared with the control group which received 30g safflower oil, an omega-6 fatty acid. It was expected that the ALA would decrease the arachidonic acid metabolites formed from the omega-6 fatty acids (which are pro-inflammatory and cause tissue destruction and pain) instead forming omega-3 metabolites which are non-inflammatory. However, this did not seem to be the case. The authors suggested that three months of supplementation was not enough to alter the omega-3:omega-6 ratio. In addition, zinc and other nutrients, such as vitamin E, are necessary to facilitate the conversion of ALA to its metabolites and these were found to be in low concentration in the rheumatoid arthritis patients.

Women’s health and cancer

Flaxseed is a good source, not only of ALA but also of lignans. Lignans are one of the main classes of phytoestrogens, the other being the isoflavones, which are found in legumes and beans, particularly soybeans. Enzymes in the gastrointestinal tract convert phytoestrogens to phenolic substances resembling the female hormone oestrogen. These substances show weak oestrogenic activity and anti-estrogenic effects, depending on the tissue and the concentration, and research has been carried out in such areas as menopausal symptoms, breast cancer and osteoporosis.¹⁷ The lignans formed from flaxseed precursors are enterodiol and enterolactone¹⁸ and although many foods contain lignans, flaxseed seems to be the richest source.¹⁹

Since urinary lignan excretion was found to be lower in breast cancer patients and higher in vegetarians (vegetarians appear to have a lower risk of cancer), studies were begun on the effects of lignans on the development of cancer. Many researchers showed that lignans have hormonal action in animal models, and epidemiological studies have suggested that lignans have a protective effect against tumours, especially hormone-related cancers such as breast and prostate cancer, although direct evidence from human studies is lacking.¹⁹

Nine healthy, premenopausal women were included in a trial to determine the dose response of urinary lignan concentration to flaxseed intake.¹⁸ A linear, dose response was seen as flaxseed ingestion increased from 5g/day to 25g/day. No plateau was seen at a dose of 25g, indicating that further increases could lead to an increased response. By the eighth day of ingestion, urinary and plasma lignans showed a significant, linear relationship, indicating that this is a good way of measuring plasma concentration. Although lignan metabolism showed variation among subjects, overall enterodiol was the lignan produced in the highest concentration. Processing did not affect lignan production, as results from raw flaxseed and processed flaxseed (muffin or bread) were similar.

To determine whether the lignans from flaxseed or the flaxseed oil were responsible for the anti-tumour properties, a study using an isolated, purified lignan precursor, secoisolariciresinol-diglycoside (SD), as well as whole flaxseed and ALA, was carried out in rats.²⁰ Supplementation was started 13 weeks after carcinogen administration, and while both flaxseed oil and flaxseed reduced the growth of existing mammary tumours, SD prevented the formation of new tumours. ALA acts by mechanisms independent of those of lignans and inhibition of cancer growth by flaxseed therefore seems to occur by a variety of mechanisms.

Other cancers have also been studied, and lignans have been shown to offer protection from cancer of the colon in rats and skin cancer in mice.¹⁹ In an in vitro experiment on human colon tumour cells, lignans reduced the proliferation of the cell lines.²¹ In this case the lignans seem to work independently of estrogenic activity and the mechanisms by which lignans inhibit tumours appear to be multifactorial, possibly also related to antioxidant action.

Kidney disease

A rat model was used to determine the effect of flaxseed on polycystic kidney disease.²² This condition involves progressive dilation of nephrons in young animals and inflammation and fibrosis with nephron loss in older animals. The rat model is useful as the disease in rats is similar to that in humans. After eight weeks of the flaxseed supplemented diet, kidney tissue and serum were analysed. Rats fed flaxseed showed a reduction in cystic change, less renal fibrosis and less macrophage infiltration, as well as lower serum creatinine levels than the control animals. The authors suggested that flaxseed supplementation may be developed to treat chronic renal injury in humans.

Constipation

In the crossover study mentioned above,⁸ in which two flaxseed muffins or two white flour muffins were eaten daily for four weeks by a small group of healthy young adults, bowel movements increased by 30 per cent per week in the flaxseed period. This could be a beneficial effect, particularly in the elderly when constipation is often a problem.

Safety

Flaxseed and flaxseed oil seem to be safe with the only notable side effect being diarrhoea at high doses in some individuals.⁸

The possible benefits of omega-3 fatty acids in pregnancy have been reported,²³ and there also appear to be significant advantages for preterm infants,²⁴ although fish oil supplements have been used rather than flaxseed. However, during pregnancy and lactation, flaxseed may have adverse effects owing to its lignan content. Such adverse effects have been found in animal studies¹⁹ and the risk must therefore be weighed against the possible benefits. Flaxseed supplements should not be recommended during pregnancy and lactation until conclusive evidence from human studies shows that they are safe.

Flaxseed oil as well as the ground seeds seem to have promising value in the treatment of various chronic diseases, particularly in the prevention of cardiac events, and may also offer protection against hormone-related cancers. This nutraceutical is easy to take either in the form of the pure oil or added to foodstuffs consumed as part of the normal diet. Its good safety profile and lack of interactions with other prescribed medicines make it an ideal supplement. Research indicates that adding ALA to the diet could benefit many individuals.