Alpha-linolenic acid (ALA, C18:3 (n-3)) is an essential fatty acid that is required for human health. The main dietary sources of ALA are plant material such as flaxseeds, hemp seeds, green leafy vegetables and walnuts, although other seeds and nuts contain smaller concentrations. Some products of animal origin such as eggs can also contain ALA, if the animals have been fed ALA rich diets. Typical intakes of ALA in Western nations range from 0.6 to 1.7 g/d and 0.5 to 1.4 g /d in men and women, respectively. Consumption of ALA is essential because it is required to form longer chain fatty acids that play important roles in cell signalling. Of particular importance are the 20-carbon eicosapentanoic acid (EPA, C20:4 (n-3)) and the 22-carbon docosahexanoic acid (DHA, C22:5 (n-3)), which accumulate in cell membranes and are used to form eicosanoids and docosanoids, respectively.
The essentiality of ALA has been questioned because it is unclear if intake is required for any function other than to supply adequate cell membrane concentrations of EPA and DHA. Plasma membrane concentrations of ALA are ~0.5 %, which is lower than EPA and DHA despite a 25-fold higher intake of the former. Therefore either ALA is depleted as it is converted to EPA and DHA, or the latter are preferentially stored in cell membranes because of their important biological functions. The absorption of ALA has been shown to be comparable to that of other fatty acids, at ~96 % absorption. Alpha linolenic acid is stored in adipose tissue, contributing 0.7 % of total fatty acids, compared to 0.1 % DHA, and undetectable levels of EPA. Whole body adipose stores therefore equate to roughly 79 and 105 g in men and women, respectively.
Body stores of ALA can be used as energy through the process of β-oxidation. Around 15 to 30% of the ingested ALA is thought to undergo β-oxidation to produce energy, with slightly higher rates in women compared to men. These rates of β-oxidation are almost twice that of ingested palmitic, stearic and oleic acids, but are surprising because it is unclear why a substance of essential characteristics such as ALA would preferentially be oxidised over other fatty acids that have the primary function of providing energy. Altering the intake of ALA in the short-term at least does not change the rate at which β-oxidation occurs. Total plasma lipid concentrations of saturated fatty acids are 20 % higher in men than women, which supports the finding that men show increased β-oxidation of ALA. However, the significance of these findings is not clear.
The conversion of ALA to EPA and DHA has been reported to be inefficient in humans. Increasing ALA intakes above 4.5 g/d increases EPA plasma phospholipid concentrations by 33 to 370 % with ALA intakes showing a linear relationship to EPA phospholipid concentrations. However, linoleic acid (LA, C18:2 (n-6)) competes for the enzymes required to convert ALA to EPA, and as a result high intakes of LA decrease EPA formation. For example, increasing consumption of LA from 21g to 50 g LA significantly decreased EPA concentrations of plasma phospholipids. However increased consumption of ALA does not increase DHA plasma phospholipid concentrations but may actually cause them to decline. The amount of ALA entering the pathway for conversion to EPA in around 0.2 to 8 %, but for DHA may be as low as 0.05 to 4 %. The first reaction, the Δ6-desaturase is the rate limiting step of the pathway.
Consumption of fish oil containing DHA and EPA may cause feedback inhibition and decrease the rate of ALA conversion. For example, consuming 6.5 g/d of DHA resulted in a 76 % and 88 % reduction in endogenous EPA and DHA synthesis, respectively. Because LA uses the same enzymes as ALA, the decrease in the production of arachidonic acid (AA, C20:4 (n-6)) with increased fish oil can be assumed to be of the same order of magnitude as EPA. In addition, the promoter region of the Δ6-desaturase gene contains a response element for the ligand-activated transcription factor peroxisomal proliferation-activated receptor-α (PPARα). Binding of DHA to PPARα suppresses the transcription of Δ6-desaturase and downregulates the conversion of ALA to EPA and DHA. In women compared to men, the conversion of ALA to EPA and DHA may be around 2.5 and 200 fold higher, respectively, possibly due to activation of the desaturation/elongation pathway by oestrogen.
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