Flaxseed oil

For over 5000 years flaxseed in its various forms has been a part of the diet of people in Asia, Africa and Europe. It has a long history of use as both a food and a medicine, with the seed being most commonly used. The oil was also popular and has been a traditional food of the Egyptians from the time of the Pharaohs to the present day. The oil is also consumed by the Chinese, who documented its medicinal properties in the Pen-T’s AO, the Great Chinese Pharmacopeia (Judd 1995). Its Latin name usitatissimum means ‘most useful’, suggesting its various uses have been recognised for centuries (Kolodziejczyk & Fedec 1995). Interestingly research into its nutritional properties and effects on human health were not studied in earnest until the 1980s (Cunane & Thompson 1995). In Australia in 1981, cultivation of a low alpha-linolenic acid variety, now known as Linola, was pioneered in an attempt to improve the stability of the oil and increase its commercial viability as a cooking oil. Such modifications were successful and resulted in ALA content <3.0% and a higher concentration of linoleic acid than the naturally occurring form (Bhatty 1995). These modified oils are not used for medicinal purposes.

Internationally it is accepted that ‘flaxseed’ refers to products for human consumption whereas ‘linseed oil’ refers to products that have been denatured, made unfit for human consumption, and used in commercial products, such as paints and varnishes.

OTHER NAMES:

Flax oil and linseed oil.

BOTANICAL NAME/FAMILY:

Linium usitatissimum (family Linaceae)

PLANT PARTS USED:

Fixed oil is derived from the seeds of the plant. Due to the highly polyunsaturated nature of the oil (.73%), extracts are obtained by cold-pressing rather than heat extraction. Flaxseed oil (FSO) is highly susceptible to photo-oxygenation, so it is packaged in opaque bottles. It is also susceptible to auto-oxidation, resulting in the production of hydroperoxides and aldehydes that can give a rancid flavour. Encapsulated FSO is considered more stable, particularly when anti-oxidants are added (Kolodziejczyk & Fedec 1995).

CHEMICAL COMPONENTS:

Flaxseed oil contains several types of fatty acids (FAs). It contains a high concentration of alpha-linolenic acid (ALA), ranging from 40% to 60%, and is the most concentrated plant source of omega-3 FA identified to date.

FSO also contains unsaturated FAs, such as linolenic, linolenic acid, linoleic acid and oleic acid. Linoleic acid (LA or C18:2n-6) and oleic acid each contribute 15% to the total FA content of the oil. Due to the range of FA present, it contains precursors for the omega-3, -6 and -9 families. FSO may also contain varying amounts of the lignan, secoisolariciresinol diglycoside (SDG), which is a precursor to enterodiol and enterolactone.

Flax seeds contain 41% fat, 28% dietary fibre, 21% protein and significantly higher amounts of lignans, which behave as phytoestrogens (Morris 2001). However, this review focuses on FSO.

Clinical note— Is FSO equivalent to the fish oils?

Flaxseed oil has been commercially promoted as the vegetarian or vegan alternative to fish oils, with many of the health benefits ascribed to fish oils also being attributed to the oil. A review of the literature suggests that FSO is unlikely to be equipotent with fish oils in the treatment of a variety of conditions.

The ALA present in FSO can theoretically undergo desaturation and elongation to synthesise eicosapentanoic acid (EPA) and docosahexaenoic (DHA), which are found in fish oil; however, most studies using oral FSO intake demonstrate only moderate increases in EPA and DHA remains unchanged (Allman et al 1995, Kelley et al 1993, Mantzioris et al 1994, Nestel et al 1997).

Although results from one early study suggest that increases in DHA levels may be achieved with long-term supplementation (Cunnane et al 1993), more recent studies fail to confirm this result (Harper et al 2006, Hussein et al 2005). Conversion rates of ALA to EPA and docosapentaenoic acid (DPA) are reported to be <10% (Harris et al 1997) and approximately 8%, respectively, whereas the DHA yield ranges from 0% to 0.5%. One explanation for this is that DHA synthesis is under separate regulatory control, a hypothesis supported by enzymatic studies (Burdge 2004). This means a 20 mL serve of FSO, providing 11.1 g of ALA, would result in a maximum of 880 mg DPA and 5 mg of DHA. Adding to this puzzle is a wide range of other variables that can inhibit the conversion of ALA into its metabolites.

For instance, high dietary intake of linoleic acid (LA), common in Western cultures, inhibits both the uptake of ALA and its conversion to long-chain metabolites. An interesting study conducted in 1998, which used radioactively labelled ALA, showed that a diet high in omega-6 fats reduced conversion by 40–50% (Gerster 1998). This adds weight to the argument that the ratios of FAs may have the primary influence on their resultant health benefits. The authors of this study suggest that the ratio of omega-6:omega-3 should not exceed 4. Other studies have reported abnormal or compromised activity of the delta-6 and delta-5 desaturase enzymes in the elderly, diabetics and patients with a variety of metabolic disorders, as well as those individuals with increased dietary intake of saturated fats, trans-fatty acids and alcohol (David & Kris-Etherton 2003). Studies using radioisotopes of ALA have revealed significant gender differences in conversion capability, with women demonstrating higher levels of FA metabolites. It is believed this is due to their higher oestrogen levels, a theory supported by the increased conversion capacity evident in women taking synthetic oestrogens and speculated as representing a physiological adaptation that ensures adequate EFA delivery to the foetus in pregnancy (Burdge 2004).

MAIN ACTIONS:

The main actions of FSO have been attributed to its high ALA content. ALA is subject to three different metabolic fates: (a) incorporation into structural, transport or storage pools, (b) beta-oxidation as an energy source and (c) elongation and further desaturation to form EPA, DPA and DHA. It appears that all three contribute to the biological effects of this oil.

ALA’s direct role in cell membrane structure is likely to be minor, with ALA representing less than 0.5% of the total FA in cell membranes and blood lipids in healthy adults. However, its limited propensity to generate the n-3 metabolites, EPA and DHA, the major FAs in cell membranes, could represent an indirect effect via this mechanism (Burdge 2004).

Studies exploring the metabolism of ALA have revealed that 22% of ALA undergoes beta-oxidation in women and 33% in men. Once broken down the carbon chain can be used as fuel or in the synthesis of cholesterol and other fatty acids such as palmitic, palmitoleic, stearic and oleic acids de novo (Burdge 2004). FSO also influences the eicosanoid production cascade via conversion of the n-3 and n-6 parent FAs in FSO to their respective metabolites. It is also thought that some of the actions of FSO may be independent of its FA content and can be attributed to the lignan SDG. This has been partly supported by research conducted by Prasad et al in 1998 and again in 1999.

ANTI-INFLAMMATORY

Metabolites of ALA and LA act as substrates for the formation of the antiinflammatory eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes (Gerster 1998). ALA suppresses AA production by interfering with the conversion of LA to AA, and reduces the biosynthesis of inflammatory eicosanoids, although not to the same extent as EPA and DHA (Morris 2001). Cytokines, another important group of inflammatory mediators, are generated in response to these eicosanoids and are influenced by changes in the n-3:n-6 ratios in cell membranes (James et al 2000).

In one study, ingestion of FSO (equivalent to 13.7 g/day ALA) for 4 weeks by healthy male subjects resulted in a 30% reduction in TNF-alpha, 31% reduction in IL-1-beta, 29% reduction in eicosanoids thromboxane B(2) and 30% reduction in PGE2 (Caughey et al 1996). In animal models ALA has consistently demonstrated eicosanoid-mediated antiinflammatory effects; however, the extent of these has been dependent on the levels of both ALA and LA in the diet, duration of use and type of tissue studied (Cunnane & Thompson 1995).

IMMUNE EFFECTS

Evidence of ALA deficiency has been reported in patients on prolonged TPN, which resulted in reduced T-helper cells to below the normal range and impaired proliferation of peripheral blood mononuclear cells. Although supplementation with small doses of ALA corrected these abnormalities, the effect of ALA on human immune cells appears to be paradoxical, with evidence of immune function inhibition at higher doses (.40 mL/day FSO) (Kelley 1995).

CARDIOVASCULAR EFFECTS

FSO and ALA have been studied as possible agents in the prevention or treatment of cardiovascular disease because ALA can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of fish oils on risk factors. The numerous studies available have suggested that FSO and ALA exert a myriad of different mechanisms in the body, which can be beneficial in cardiovascular disease; however, inconsistent results have meant that much is still unknown and more research is required.

ANTITHROMBOTIC AND ANTIPLATELET ACTIVITY

The question of whether supplementation with ALA affects platelet aggregation remains unclear. A major determinant appears to be the degree of conversion to EPA (Garg et al 1989). When there is an increase in total EPA and reduced AA, due to ALA inhibition of LA conversion, the result is EPA replacing AA in the cell membrane and a decrease in thromboxane synthesis. In addition, SDG, another component of FSO, is metabolised to enterolactone and enterodiol and these substances may have antiplatelet-activating factor activity. Due to the variable lignan content of FSO it is difficult to determine the clinical significance of this (Prasad 1999). Studies assessing the actual anti-aggregatory effect of FSO in humans have produced mixed results.

REDUCED ENDOTHELIAL INFLAMMATION

A number of studies have confirmed that consumption of high-dose FSO reduces endothelium inflammation. One study assessing the cardiovascular effects of a diet in which 6.5% of total kilocalorie intake was contributed by ALA and compared with the Standard American Diet (SAD) showed that the ALA-enriched diet produced a 75% reduction in C-reactive protein, a 19% reduction in cellular adhesion molecule, and a 15.6% reduction in vascular cellular adhesion molecule (VCAM) (Zhao et al 2004). An earlier study had reported these findings, demonstrating a 28% reduction in VCAM with additional reductions in soluble E-selectin (17%) (Thies et al 2001).

LIPID-LOWERING

Whole flaxseed is the form most commonly investigated in lipid-lowering studies, because the high fibre content and ALA appear to act synergistically, whereas there are few studies using FSO. Those that have been conducted with FSO have produced conflicting results with an almost 50/50 weighting of research showing no effect or a positive one. At worst FSO has resulted in increases in fasting triacylglycerol concentrations and lower HDL-cholesterol (Bemelmans et al 2002, Finnegan et al 2003, Wilkinson et al 2005) and at best it has been described in earlier studies as having comparable effects with bio-equivalent doses of fish oils (Harris 1997, Singer et al 1986).

The reality probably lies somewhere in between; however, further investigation is required. The results of the small study of 57 men by Wilkinson et al (2005), who substituted 45 g of fat per day with 15 g/day ALA derived from FSO over 12 weeks adds to the puzzle. While confirming the mixed cardiovascular effects noted above, this treatment group also demonstrated a reduction of total cholesterol by 12.3% in comparison to a reduction of 7.3% in the group receiving equivalent LA.

The same equivocal trend is evident from studies assessing the effects of FSO on lipoproteins. Zhao’s trial (2004) using an ALA-enriched diet showed that this change resulted in a reduction in apololipoproteins A1 and B, the latter by almost 10%.

ANTI-ARRHYTHMIC

Three recent studies have identified an anti-arrhythmic effect mediated by ALA (Albert et al 2005, Ander et al 2004, Christensen et al 2005) although one meta-analysis concluded otherwise (Mathan et al 2005). Although the majority of research has been conducted in animals, one of the most interesting human trials involved 106 women with a mean age of 59.5 years referred for coronary angiography due to suspected coronary artery disease. Following adipose sampling for ALA levels and monitoring of 24-hour heart rate variability (HRV), it was concluded that a positive and independent association was present between ALA in adipose tissue and HRV, which was even stronger in smokers (Christensen et al 2005). ANTI-ATHEROGENIC Earlier positive findings and recent promising epidemiological data have been substantially challenged by RCTs of FSO in atherosclerosis.

Following earlier positive outcomes in cardiovascular disease trials with whole flaxseed, a 1999 study showed that a low-ALA variety could produce comparable results with the earlier trials, suggesting that the anti-atherogenic properties of flaxseed are independent of its ALA content (Prasad 1999). More recent large-scale epidemiological studies continue to suggest a relationship between higher ALA intake and reduced coronary artery calcification (Djousse et al 2005); however, there is ongoing criticism that important variables have not been sufficiently accounted for, such as corresponding reductions in trans-FAs (Harris 2005, Wilkinson et al 2005).

ANTIPROLIFERATIVE

ALA has demonstrated the capacity to inhibit tumour progression in animal models of mammary tumour (Chen et al 2002, Cognault et al 2000); however, the clinical significance of these findings needs to be examined further. An immunostimulant action, which is both eicosanoid and non-eicosanoid mediated, has been suggested as one possible mechanism of action. Another theory suggests that through ALA’s competitive inhibition of LA, tumour cells may not receive sufficient LA, which would inhibit further cell growth (Johnston 1995). It is interesting to observe that higher dietary ALA intake is associated with a reduction in cancer deaths; however, this is not seen with higher EPA/DHA intakes, suggesting that the protective effect is not reliant on the conversion of ALA to EPA/DHA (Cunnane 1995). In addition, results from epidemiological studies show an association between low ALA consumption in humans and increased cancer deaths in general (Dolecek 1992).

Animal studies testing SDG and its metabolites from the seeds have produced promising results and suggest that they may act as selective oestrogen receptor modulating agents and therefore play a protective role against oestrogen-dependent cancers (Kitts et al 1999, Wang et al 2005).

INSULIN SENSITISING

Preliminary animal studies suggest a protective role for ALA against the development of insulin resistance and an ability to counter the associated oxidative stress (Ghafoorunissa & Natarajan 2005, Suresh & Das 2003). Clinical trials are required to determine the significance of these findings.

CLINICAL USE:

REDUCED MORTALITY IN CORONARY HEART DISEASE

The most likely mechanism by which ALA may prevent coronary heart disease (CHD) mortality is by reducing cardiac arrhythmia. In Western populations, almost 50% of all deaths from cardiovascular disease can be attributed to sudden cardiac death and the majority of sudden deaths are directly caused by acute ventricular arrhythmia (Brouwer et al 2004). A review in 2001 (Lanzmann-Petithory) and a meta-analysis of three studies in 2004 (Brouwer et al) both found in favour of a protective effect from increased ALA consumption against fatal CHD (RR 0.24).

The dose associated with this trend was small; only 1–3 g/day ALA higher than controls (Brouwer et al 2004). A study published in 2005, which derived data from the Nurses’ Health Study (Albert et al), found that women consuming ALA in the highest two quintiles had a 38–40% lower risk of sudden cardiac death than women in the lowest quintile; however, the protective effect did not extend to other fatal forms of CHD or non-fatal myocardial infarction. Much criticism has been directed at those researchers wanting to extrapolate prescriptive advice from these findings. An editorial by Harris (2005) notes that only one primary prevention study with ALA in CHD has been conducted and that was in the 1960s. The 1-year trial involved 13,578 Norwegian men and compared 10 g of FSO (providing 5.5 g/day ALA) with a sunflower seed placebo. In the analysis there was no demonstrable difference in end-points between the two groups. Recent attempts to explain this lack of effect, such as high baseline n-3 consumption by this population, appear to be well founded (Mozaffarian et al 2005). There is an urgent need for RCTs using FSO in suitable populations to clarify the relationship between ALA and CHD mortality.

ANTICLOTTING

There has been a surprising number of studies investigating the influence of ALA from FSO on coagulation and fibrinolysis, and enormous variation in results. Methodological issues have plagued the overall quality of evidence, with small sample sizes, inconsistent methodologies and diverse sample characteristics making interpretation difficult.

One early study compared different dietary ratios of n-6 and n-3 EFAs in relation to prostanoid production in a group of normolipidaemic men (Kelley et al 1993). The high ALA dietary intervention constituted an overall n-6:n-3 ratio of 2.7 versus control ratios of up to 27.4. Following the 18 days of the intervention, groups showed significant differences in measured outcomes, notably, that 6-keto-PGF1-alpha was significantly higher following the high ALA diet but no evidence of significant effect on bleeding time or thromboxane B2 production. A second study published in the same year also failed to show an effect on clotting; however, the dose of FSO used was only 4.3 g/day (Kelley et al 1993). In contrast, the results of a study using a much larger dose of 40 g/day of FSO over 23 days in 11 healthy men showed that FSO significantly reduced collagen-induced aggregation response when compared to 40 g/day sunflower seed oil (Allman et al 1995). A follow-up study of 29 healthy males that was conducted over 6 weeks investigated the effects of a diet in which approximately 7% of the total kilocalories from polyunsaturated fat was made up of either an ALA-rich (n-3:n-6 = 1:1.2) or LArich diet (n-3:n-6 = 1:21). The ALA-enriched diet resulted in triple the EPA phospholipid levels compared to the LA-enriched diet, but had no demonstrable effect on coagulation or fibrinolysis, other than an increase in the ratio of activated protein C.

The authors speculated that the latter finding may still prove significant, but suggest that future studies should be conducted in patients with vascular pathology, as healthy clotting profiles may have obscured the true effects of FSO (Allman-Farinelli et al 1999). In the same year another group of Australian researchers published the results of their study of 17 vegetarian men who were assigned to either a low- or high-ALA diet (derived from FSO) for 28 days following a run-in baseline diet for 14 days. Again there were no significant differences in prothrombin time, activated partial thromboplastin time, or plasminogen activities with the different ALA diets, despite increases in EPA and DPA levels (Li et al 1999). Since 1994 Mutanen and Freese have conducted many studies assessing the effect of ALA and LA:ALA ratios on haemostatic factors (Freese & Mutanen 1997, Freese et al 1994, Mutanen & Freese 2001). Their 1997 study was the largest and involved a sample of 46 subjects who were given FSO to provide 5.9 g/day ALA or a fish/sunflower oil combination equal to 5.2 g/day EPA/DHA over 4 weeks.

Extensive analysis of the sample throughout the intervention, as well as at the 12-week followup, revealed no difference in collagen-induced platelet aggregation, thromboxane production or bleeding time between the two groups, suggesting equivalent anticoagulant effects for FSO and fish oil when consumed in comparable quantities This was despite smaller increases in EPA levels in the platelets of the subjects taking FSO. The largest and most recent trial (Finnegan et al 2003) compared the effects of small increases in ALA (4.5 or 9.5 g/day) and EPA and DHA (0.8 or 1.7 g/day EPA+DHA) intake on blood coagulation and fibrinolytic factors over 6 months. The randomised, placebo-controlled, parallel study of 150 moderately hyperlipidaemic subjects found no significant differences in coagulation or fibrinolysis for any intervention. Currently the evidence is equivocal, but may indicate a minor anti-aggregatory role for FSO in high doses. Further research, with more heterogeneous designs, is required to form any valid conclusion.

ENDOTHELIAL FUNCTION

In one 12-week study of healthy subjects aged 55–75 years, low levels of ALA (equivalent to approximately 5 mL/day of FSO) were shown to decrease some markers of endothelial activation (Thies et al 2001). More specifically, ALA decreased the plasma concentrations of soluble VCAM-1 by 16% and soluble E-selectin by 23%.

LIPID-LOWERING

The largest and most recent trial involved over 150 moderately hyperlipidaemic patients in a double-blind placebo-controlled 5-arm parallel design conducted over 6 months. Two groups received FSO at different doses (equivalent to 4.5 g/day and 9.5 g/day of ALA), two groups received bioequivalent levels of EPA/DHA and one group received LA and served as a control group. Although the higher ALA dose induced comparable changes in serum and cell membrane EPA levels to the fish oil group, ALA failed to significantly lower lipid levels, whereas EPA and DHA reduced triacylglycerides (Finnegan et al 2003). Alternatively, a shorter study of only 2 weeks supplementing with much higher doses of FSO (60 mL/day) or sunflower oil or 130 g/day of mackerel in hypertensive males produced positive results.

Subjects taking either FSO or consuming fish experienced an equal decrease in serum triglycerides, total cholesterol, and LDL-cholesterol (Singer et al 1986). Interestingly, FSO intake resulted in only marginal increases in EPA levels, suggesting lipid-lowering activity is not reliant on conversion to EPA. One possible explanation for this comes from the results of a number of trials conducted by Prasad (Prasad 1997, 1999, Prasad et al 1998), who investigated low- ALA FSO and later isolated extracts of the lignan SDG and found significant lipidlowering effects in animal models. In rabbits, administration of the lignan at high doses produced significant changes to blood lipids, including a 33% reduction in total cholesterol, 35% reduction in LDL-cholesterol and an astonishing increase of over 140% in HDL-cholesterol by week 8 (Prasad 1999).

As exciting as these results are, it is difficult to determine the clinical significance of these findings because the lignan content of FSO is variable. It is possible that the high dose of FSO (60 mL/day used by Singer 1986) contained a substantial amount of SDG, which could explain the effects seen; however, this is speculation.

Clinical Note— Are vegetarians at risk of omega-3 deficiency?

Omnivores can obtain n-3 long-chain PUFAs in two ways: from the partial conversion of dietary ALA or directly through the consumption of fish, eggs, or animal products (Li et al 1999). Lacto-ovovegetarians obtain n-3 EFAs from the conversion of plant-based ALA and a limited amount of preformed EPA and DHA from milk, dairy products, and eggs; however, their EFA content is highly dependent upon the animals’ diet. In contrast, strict vegetarians and vegans are at risk of inadequate n-3 EFA, DHA and EPA intake because they are solely reliant on plantbased ALA, which has poor conversion to n-3 EFA metabolites in the body and they have no dietary intake of preformed DHA or EPA.

This has been demonstrated in studies in which lower plasma and platelet levels of n-3 EFAs have been identified in vegetarians compared with omnivores, together with lower EPA and DHA levels. For vegetarians and vegans, increased consumption and conversion of ALA has been proposed as a strategy to ensure omega-3 adequacy; however, the evidence to date suggests this is not effective (Burdge 2004, Phinney et al 1990). Average daily intake of ALA has been estimated at 1.5 g in the general population and may be lower in vegetarians and vegans. Based on current conversion calculations, general consumption levels already fall short of EPA and DHA requirements.

Studies investigating increased ALA consumption at 9.5 g/day, the equivalent of approximately 17 mL FSO, found this increased EPA and DPA, yet failed to improve DHA concentrations, which is further proof that ALA is not an effective substitute for animal-derived omega-3 EFAs (Burdge 2004). To complicate matters, there is evidence suggesting that high intakes of ALA downregulate the delta-6-desaturase enzyme, therefore inhibiting its own conversion (Gerster 1998). Vegetarian diets are also notoriously rich in the n-6 EFA, LA, which if consumed in significantly higher quantities than omega-3 will further retard conversion of ALA (Kris-Etherton & Skulas 2005). Vegans and vegetarians are recommended to consume additional sources of ALA, such as algae, that may contain some preformed EPA and DHA in an attempt to reduce risk of deficiency (Kris-Etherton & Skulas 2005, Li et al 1999).

INSULIN SENSITIVITY/METABOLIC SYNDROME

It has been proposed that FSO may be of benefit in insulin resistance (IR) based on its possible cardioprotective activities; however, direct evidence of improved insulin sensitivity remains elusive. One small study published in 1997 demonstrated improved systemic arterial compliance in 12 subjects with suspected IR, fed a high dose of ALA over 12 weeks, although an additional finding in this study was evidence of slight deterioration in insulin sensitivity (Nestel 1997). Another study using relatively low-dose FSO (1.7 g/day ALA) in normoglycaemic adults found no changes in glycaemic response (Curran et al 2002). Further investigation using higher doses of FSO and ALA is required to determine whether there is a role for FSO in this condition.

ANTICANCER EFFECTS

Breast and colon cancer Bougnoux et al (1994) made an important observation when they demonstrated an inverse relationship between ALA levels in breast tissue and risk of lymph node involvement and visceral metastases in breast cancer. This has been followed up with larger studies of similar design (Klein et al 2000, Maillard et al 2002) and one meta-analysis, all yielding comparable results (Saadatian-Elahi et al 2004). The data indicate that those women with the highest breast tissue concentrations of ALA have a relative risk of breast cancer between 0.36 and 0.39, while other FA levels fail to exhibit a statistically significant relationship. Interestingly, an epidemiological study has identified an association between low consumption of ALA in humans and increased cancer deaths in general (Dolecek 1992). Currently the only evidence from interventional studies using FSO as a chemoprotective agent is provided by animal trials, which demonstrate that dietary FSO is effective in preventing colon tumour development and malignant mammary tumours (Dwivedi et al 2005).

Prostate cancer There is much debate surrounding research into the hypothesised link between ALA and the risk of prostate cancer. Giovannucci, a prolific prostate cancer researcher, has contributed to numerous papers on this topic, deriving data from large epidemiological or prospective cohort studies including The Health Professionals Follow-Up, The Physician’s Health Study and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Gann et al 1994, Giovannucci et al 1993, Leitzmann et al 2004, Mannisto et al 2003). The conclusions oscillate between a positive independent association between increased ALA intake and prostate cancer risk (Gann et al 1994, Giovannucci et al 1993, Leitzmann et al 2004) to no significant association (Mannisto et al 2003). Further support of ALA as a risk factor has come from a large Norwegian epidemiological study (Harvei et al 1997), a review by Astorg and a meta-analysis by Brouwer et al in 2004. Although the majority of published data appear to implicate ALA as a prostate cancer risk factor, it is worthy of note that none of the trials were interventional and many rely exclusively on food frequency questionnaires rather than independent biochemical indices of ALA.

Other researchers have also presented sound arguments against this theory, such as those articulated by de Lorgeril and Salen (2004), which query the quality of evidence being considered, the exclusion of trials that demonstrated minor risk reduction with increased ALA intake (Schuurman et al 1999) and other weaknesses of the study designs. Additional criticisms include the lack of distinction in the sources of dietary ALA, with red meat, an independent risk factor for prostate cancer, being a major dietary source of ALA in some studies (Brouwer et al 2004). Until interventional trials are conducted a resolution on the matter is not possible.

DOSAGE RANGE:

· Anticlotting: 5.9 g/day ALA
· Improved endothelial function: 2 g/day ALA
· Lipid-lowering: 60 mL/day FSO
· Reduced CHD mortality: 1–3 g/day ALA

A key consideration with FSO supplementation is product quality. Due to the high potential for FSO to become oxidised, ingestion of inadequately manufactured or preserved FSO could result in higher intakes of peroxides. It is recommended that only refrigerated FSO packaged in opaque containers be used. Once opened, the product should be consumed within a few weeks of opening and kept stored in the fridge.

ADVERSE REACTIONS:

Flaxseed oil may cause loose stools in some individuals. There is a report of an allergic reaction to FSO, with a 40-year-old woman experiencing ocular pruritis and weeping followed by generalised urticaria and nausea, and vomiting within 10 minutes of taking a spoonful of linseed oil. A subsequent skin prick test produced a positive response to linseed. It remains unclear, however, whether this patient consumed FSO or linseed oil, which is denatured and unfit for human consumption (Alonso et al 1996).

SIGNIFICANT INTERACTIONS:

None known

CONTRAINDICATIONS AND PRECAUTIONS:

· Hypersensitivity to flaxseed/linseed
· Prostate cancer

There are a number of studies that link increased ALA intake with a higher risk of prostate or aggressive prostate cancer. Although the evidence is preliminary and widely debated, it is recommended that at-risk individuals avoid high dose consumption of FSO and only consume FSO that is packaged in opaque containers and refrigerated.

PREGNANCY USE:

There is no evidence to suggest safety concerns for FSO.

PRACTICE POINTS/PATIENT COUNSELLING:

· Good quality, cold-pressed FSO is a good source of the essential fatty acid alphalinolenic acid (ALA), which is often deficient in the Western diet.

· The polyunsaturated fatty acids found in FSO, particularly ALA, are precursors of eicosanoids and influence many important physiological processes. Additional actions may be attributed to the variable amount of lignan present in FSO, but which is found in higher concentrations in the actual seed.

· FSO has demonstrated anti-inflammatory, immunological, minor antiplatelet and chemopreventive effects and a range of beneficial actions within the cardiovascular system; however, large RCTs are still required to determine the role of FSO in clinical practice.

· FSO is not an adequate substitute for animal sources of n-3 EFAs. Most studies of oral FSO demonstrate only moderate increases in EPA, while DHA remains unchanged. Strict vegetarians and vegans using FSO as n-3 EFA substitute may be at risk of EPA and DHA deficiency.

· There is some evidence to suggest that daily ingestion of an additional 1–3 g of ALA (equivalent to 5 mL FSO) may reduce the incidence of some cancers and coronary heart disease mortality; however, this remains speculative.

ANSWERS TO PATIENTS’ FREQUENTLY ASKED QUESTIONS:

What will this supplement do for me?
Regular consumption of flaxseed oil, in the presence of balanced linoleic acid (omega-6) intake, may reduce cardiovascular mortality and possibly reduce the risk of some cancers; however, this remains speculative.

When will it start to work?
This will depend on the dosage taken and indication for use.

Are there any safety issues?
Long-term high doses may compromise immune function in susceptible individuals. Preliminary evidence suggests a possible link between high ALA intake and increased risk of prostate cancer; however, this is controversial.

SOURCES

REFERENCES:

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