Gender-specific fatty acid profiles in platelet phosphatidyl-choline and -ethanolamine

Abstract

Previous studies suggested that women synthesise docosahexaenoic acid (DHA) more efficiently from their precursors than men. This study investigated the relationship between diet, platelet phospholipids fatty acids and gender. Dietary intake and platelet phosphatidyl-choline (PC) and phosphatidylethanolamine (PE) fatty acids were determined in Caucasian 40 men and 34 women. Absolute and %energy intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and DHA, and the ratios of total n-6/n-3 PUFA and linoleic/alpha-linolenic acids did not differ between the sexes. However, women had higher DHA in PC (1.19 vs 1.05 wt%, p<0.05) and PE (3.62 vs 3.21 wt%, p<0.05) than men. Also EPA (1.10 vs 0.93 wt%, p<0.05) was higher in women's PE. Conversely, men had elevated AA and total n-6 fatty acids in PC. The higher platelet DHA levels and lower platelet AA/EPA and AA/DHA ratios in women of child-bearing age compared with men, may lead to less platelet aggregation and vaso-occlusion.

Introduction

The essential fatty acids, linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3) and their long-chain polyunsaturated derivatives (LCPUFA) are indispensable for human development and optimum health. Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are considered the most important functional LCPUFA in central nervous system and vision. DHA and AA are found in high concentrations in structural lipids of the central nervous system and have been shown to be important for brain development and function [1], [2], [3]. Adequate accretion of both DHA and AA in brain and retina is particularly important during the rapid brain growth, which takes place in the perinatal period [3]. Moreover, n-3 LCPUFA contribute significantly to the biophysical properties of the phospholipid bilayer by providing an appropriate environment for the activities of membrane-associated proteins [4]. The incorporation of n-3 LCPUFA in cell membranes also modifies eicosanoid production resulting in altered platelet and leukocyte reactivities [5], [6]. The accumulation of eicosapentaenoic acid (EPA, 20:5n-3) and DHA in circulating blood platelets provides a partial replacement of AA in membrane phospholipids resulting in less production of pro-aggregatory and vaso-constrictive thromboxane (TX) A₂ upon platelet stimulation due to the competitive inhibitory effects of EPA and/or DHA on cyclo-oxygenase activity [7], [8]. This could result in less platelet aggregation and thrombosis and may contribute to the beneficial effects of n-3 LCPUFA on cardiovascular risk.

For optimal cardiovascular health, the International Society for the Study of Fatty Acids and Lipids (ISSFAL) recommends a minimum combined intake of EPA and DHA of 500 mg/day for healthy adults [9]. Dietary sources of preformed EPA and DHA are primarily fish and seafood [10]. In the UK and other Western countries dietary intakes of EPA and DHA are low compared with ALA or LA intakes. In the British diet, estimated average daily intakes are 1.55 g ALA, 60 mg EPA and 100 mg DHA [11]. This suggests that the conversion of ALA to EPA and DHA may be important for providing n-3 LCPUFA for cell membranes. The de novo synthesis of AA, EPA and DHA from their precursors involves a series of desaturation, elongation and β-oxidation steps [12]. The ability of humans to convert ALA into n-3 LCPUFA has been studied using two approaches: increased dietary ALA consumption or use of stable-isotope-labelled ALA. In men, both study approaches showed conversion to EPA and docosapentaenoic acid (DPAn-3, 22:5n-3), but limited conversion to DHA (reviewed in Burdge and Calder [13]). Using a stable-isotope tracer technique, Burdge and co-workers found that women of reproductive age had a much greater capacity to convert ALA to DHA compared with men of a similar age [14], [15]. In agreement with these results, Pawlosky et al. [16] reported that, when subjects subsisted on a beef-based diet (containing low amounts of n-3 LCPUFA), the fraction of plasma DPAn-3 which was converted to DHA (so-called ‘rate constant coefficient’) was much greater in women than in men. The larger rate constant coefficient in women led to a nearly 3-fold higher amount of DPAn-3 utilised for DHA synthesis compared with men. The implication of these findings is that conversion of DPAn-3 to DHA, which requires both Δ6-desaturase activity and peroxisomal β-oxidation, is modified by gender and may be regulated independently from the activity of earlier steps in the pathway. Furthermore, partitioning of ALA towards β-oxidation and carbon recycling into saturated (SFA) and monounsaturated fatty acids (MUFA) appears to be lower in women than in men [14], [15]. This means that women would have a greater availability to convert ALA to longer-chain n-3 PUFA than men who use fatty acids as an energy source to a greater extent. It is plausible that oestrogen may act as an agonist of DHA synthesis, as women taking an oral contraceptive pill had higher concentrations of labelled DHA in their circulation than those who did not [14], [17]. In addition, treatment of postmenopausal women with the selective oestrogen receptor modulator raloxifene or hormone replacement therapy (using conjugated equine oestrogens plus medroxy-progesterone acetate) increased plasma cholesterol ester DHA concentrations [18].

So far, four studies have been undertaken in human subjects to investigate if the assumed gender-related differences in n-3 PUFA metabolism are reflected in circulating plasma levels of n-3 LCPUFA (reviewed in Childs et al. [19]). Although these studies vary in sample size, extent of dietary control and blood lipids analysed, they all found that women had higher plasma/serum DHA concentrations compared with men [17], [20], [21], [22]. Two studies also reported lower circulating concentrations of EPA and DPAn-3 in women compared with men [20], [21], which may indicate either a greater conversion of EPA and DPAn-3 into DHA or their displacement from blood lipids by DHA.

To our knowledge, no study has directly compared n-3 LCPUFA composition of platelet membrane in men and women of similar age consuming their habitual diets. Hence, the present study investigated if there is gender difference in the n-6 and n-3 fatty acid composition of platelet phospholipids.