Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics

Abstract

Background: Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders.

Methods: The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes.

Results: Supplementation with several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%.

Conclusions: This study shows that dietary supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Figure 1

Pathways for metabolism of n-6 (left) and n-3 (right) PUFAs in humans. The pathway depicts the synthesis of 20 and 22 carbon PUFAs from the essential, dietary PUFAs, α-linolenic acid (n-3) and linoleic acid (n-6). The PUFAs derived from borage oil (linoleic and gamma-linolenic acids, both n-6) and echium (α-linolenic, n-3; stearidonic, n-3; linoleic and gamma-linolenic acids, both n-6) would be expected to enter the pathways at the indicated points.

Figure 2

Effects of dietary supplementation with borage and echium seed oils on concentrations of plasma n-3 fatty acids. Data are expressed as a percentage of total plasma fatty acids and are shown for ALA (open bar), SDA (black bars), EPA (gray bars), DPA (cross-hatched bars), and DHA (white striped bars). Fatty acid profiles were monitored during the time course of the study beginning at baseline (Pre), during supplementation (weeks 1–3) and during the washout phase (w/o1-3). Data are mean ± SEM for each group. Statistically significant rises in SDA, EPA and DPA were noted over time (p < 0.0001) with significant differences among groups (p = 0.004).

Figure 3

Effects of dietary supplementation with borage and echium seed oils on concentrations of plasma n-6 fatty acids. Data are expressed as a percentage of total plasma fatty acids and are shown for GLA (black bars), DGLA (white bars), and AA (gray bars). Fatty acid profiles were monitored during the time course of the study beginning at baseline (Pre), during supplementation (weeks 1–3) and during the washout phase (w/o1-3). Data are mean ± SEM for each group. Statistically significant rises in GLA and DGLA were noted over time (p < 0.0001) with no statistically significant differences among groups.

Figure 4

Dietary supplementation with borage and echium seed oils decreases FcϵRI-dependent cysteinyl leukotriene generation by peripheral blood basophils. Cysteinyl leukotriene generation is shown prior to (●, closed circles) and one week (∆, open triangles), two weeks (□, open squares), and three weeks (○, open circles) after dietary supplementation with one of four borage and echium seed oil combinations (Groups 1–4, respectively) in response to buffer alone, control IgG1 (1.0 μg/ml, IgG), and 15A5, an activating antibody against FcϵRI (0.01 to 1.0 μg/ml). Due to technical errors, data are not available for one subject in each of groups 1, 3, and 4. In addition, basophils from one subject in each of groups 3 and 4 failed to release leukotrienes upon stimulation, a well described phenomenon due to impaired signaling through Syk. Data are expressed as a percentage of maximal cysteinyl leukotriene generation in each subject and are expressed as means ± SEM. Statistically significant suppression of ex vivo leukotriene generation was noted (p < 0.0001) with a significant difference between groups (p < 0.0001).

Figure 5

Cessation of dietary supplementation reverses inhibition of FcϵRI-dependent cysteinyl leukotriene generation by peripheral blood basophils. After 3 weeks of dietary supplementation (open bars), subjects stopped ingesting borage and echium seed oils. FcϵRI-stimulated basophilic cysteinyl leukotriene generation was measured at one (gray bar), two (cross-hatched bar) and three weeks (solid bar) of washout. Data are shown for maximal cysteinyl leukotriene generation in response to 1.0 μg/ml 15A5. Data are expressed as a percentage of maximal cysteinyl leukotriene generation in each subject and are expressed as means ± SEM.

Figure 6

Dietary supplementation with borage and echium oils decreases A23187-stimulated total leukotriene generation by peripheral blood neutrophil. Leukotriene generation is shown prior to (●, closed circles) and one week (∆, open triangles), two weeks (□, open squares), and three weeks (○, open circles) after dietary supplementation with one of four borage and echium seed oil combinations (Groups 1–4, respectively) in response to buffer alone and increasing concentrations of the calcium ionophore, A23187 (0.1 to 10 μM). Total leukotriene generation is the sum of LTB₄, 5-HETE, and, where measurable, all-trans-LTB₄ isomers. Data are expressed as means ± SEM. Statistically significant suppression of ex vivo leukotriene generation was noted (p < 0.0001) with a significant difference in effect between groups (p = 0.02).