Introduction

Flaxseed oil is a rich source of essential fatty acids (EFAs), particularly the omega-3 fatty acid alpha linolenic acid (ALNA). ALNA and linoleic acid (LA, an omega-6) are considered to be the two primary EFAs [1]. Other food sources rich in ALNA are some vegetable oils such as canola oil and soybean oil, walnuts, dairy products, beans, broccoli, and leafy greens. However, these sources generally do not contribute much ALNA to the diet, especially since soybean oil is usually partially hydrogenated, which decreases ALNA and increases trans fatty acid content [2]. Supplementation with flaxseed oil is a good way to increase the ALNA content of the diet, and multiple studies indicate that flaxseed or flaxseed oil favorably alters the tissue omega-6:omega-3 ratio [3-5]. Flaxseeds also have additional components, such as lignan precursors, which may play a role in preventing breast and other cancers [6], but these are not found in appreciable amounts in commercial flaxseed oil products.

There are numerous reasons why increasing dietary omega-3 fatty acid content is important. First, body stores of LA are high and can last for quite some time compared to ALNA, and the oxidation rate of ALNA is also higher. Intake of LA usually far exceeds requirements, and this is not the case with ALNA [1]. An imbalance between intake of omega-6 and omega-3 fatty acids is very common, especially in Western European and American populations [7], and this imbalance has been implicated in cardiovascular disease, depression, cancer, diabetes, arthritis and other inflammatory conditions, and other disease states and conditions [7-9]. This article will place the focus on the role of dietary ALNA on body composition and cardiovascular disease and compare ALNA to the longer-chain n-3 PUFAs (LC-PUFAs), docosohexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

Arachidonic acid and lipogenesis

Arachidonic acid (AA) is an omega-6 fatty acid derived from LA. Although the conversion rate is low, the high intake of LA in most diets still affects AA concentrations [8]. Arachidonic acid is converted into specific leukotrienes, prostaglandins and thromboxanes, excessive production of which have been implicated in arthritis, asthma, cardiovascular disease, and other inflammatory disorders. Conversely, ALNA is metabolized into LC-PUFAs which competitively inhibit the AA cascade [7]. A role of EFA content in the diet on body fat is relatively well established in animals, although human research is still lacking. Dietary fats rich in ALNA and other omega-3's have both been reported to prevent adipose tissue development in rodents. Conversely, high tissue AA content has been implicated in promoting adipogenesis [10].

Arachidonic acid is a precursor to prostaglandin I2 (prostacyclin) via the cyclooxygenase (COX) pathway. Prostacyclin upregulates expression of two CCAAT-enhancer binding proteins, C/EBP-beta and C/EBP-delta, which then upregulate peroxisome proliferator-activated receptor gamma (PPAR-gamma); the functional consequence is that prostacyclin promotes adipogenesis in both rat and human preadipocytes. Prostacyclin also binds to PPAR-delta, and this may also lead to upregulation of PPAR-gamma. The fact that the adipogenic effect of AA can be reduced by COX inhibitors (such as aspirin) lends support to an important role in prostacyclin signalling in the development of adipose tissue. Dietary ALNA can decrease synthesis of AA from LA, through mechanisms such as competitive inhibition of the delta6 desaturase enzyme, and this could explain the reduction in fat mass seen in mice fed ALNA [10]. In addition, the LC-PUFA metabolites of ALNA can further stimulate fatty acid oxidation [11-12].

Cardiovascular disease

In confirmation of results from animal studies, epidemiological studies strongly suggest that ALNA, like EPA and DHA, reduces the risk of and fatality rates from cardiovascular disease. Mechanisms include prevention of arrhythmias, blood pressure reduction, anti-inflammatory effects, inhibition of platelet aggregation, and possibly a reduction in serum lipids [2, 13]. Epidemiological studies of various types find an association between increased intake of ALNA and lower risk of coronary artery disease and ischemic heart disease, lower risk of myocardial infarction, lower rate of cardiovascular disease mortality, and lower all cause mortality [1-2, 13-14]. Both primary and secondary prevention trials have provided further evidence for many of these benefits [13].

Not all studies have shown a benefit, however. Although the evidence is strong for most of the mechanisms of action, results from studies on the effect of ALNA on lipid profiles have been inconsistent [13-15]. The results from some epidemiologic studies are equivocal. This may be due to flaws or inconsistencies in study design [16]. It may also be because the effect of ALNA is more pronounced in populations with low intake of LC-PUFAs from fish. Finally, diets high in ALNA also tend to be high in trans fats, which increase cardiovascular disease risk and could confound results [2].

ALNA vs. EPA/DHA

The majority of the biological effects of ALNA are generally attributed to conversion to EPA and then DHA via desaturation and elongation. These fatty acids generally have all of the same benefits of ALNA, and then some. In human and animal studies, ALNA successfully raises tissue levels of EPA, but the conversion rate is low (less than 10%) [17]. The remaining ALNA is either beta-oxidized for other purposes or partitioned into certain tissues, such as skin [17-18]. The conversion rate to DHA is very low, so both ALNA and EPA supplementation generally fail to significantly increase tissue DHA content. It is likely that this is because DHA synthesis is regulated largely independently of tissue EPA content [17].

There is some debate over whether ALNA has important activity independently of its conversion to EPA/DHA, as the biological roles of ALNA are not well known. Research suggests that ALNA has independent anti-arrhythmic effects, effects on cholesterol metabolism and blood lipids, and anti-inflammatory effects [2, 16, 19-20]. In some tissues, such as the brain, ALNA may mimic some of the effects of the longer chain omega-3's [21]. ALNA may also play an important role in skin function [22].

Conclusion

Flaxseed oil is a good source of EFAs and a good way to change the omega-6/omega-3 ratio in the diet. It is associated with numerous health benefits. However, it is still debatable whether or not it will provide a benefit independent from EPA and DHA, which can be obtained in the diet through fish oil supplementation. Future studies may help to further define the biological role of ALNA.

If you have any questions or comments regarding this article, please email dvdtlsn@bulknutrition.com.


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