Antithrombotic potential of dihomo-gamma-linolenic acid in man.

Abstract

SummaryThe effects of orally ingested dihomo---linolenic acid (DHLA), the natural biosynthetic precursor of prostaglandin El (PGE,), were assessed in human volunteers. Single doses of DHLA (0 1-2g) increased the proportion of DHLA relative to arachidonic acid in plasma and platelets and also increased the ex-vivo capacity of platelets to produce PGE, and PGE2. More pronounced effects were observed during sustained treatment (five days to four weeks) when DHLA also accumulated in red cell membranes. These biochemical changes were accompanied by potentially antithrombotic changes in haemostatic function. The most common effect, which was consistently detected after 0 1-g single doses of DHLA or its methyl ester, was a decrease in plasma heparin-neutralising activity. Inhibition of platelet aggregation induced by adenosine diphosphate was also detected, though this was generally less pronounced. Sustained treatment in one subject also produced definite inhibition of ristocetininduced platelet aggregation. There was only one possible adverse effect-a transient cough in a subject with a history of asthma.

Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase products in platelet activation

“…Rap1 is an essential GTPase involved in regulation of platelet function, and inhibiting its activation in the presence of a strong activating agonist, such as PAR1-AP, suggests an important regulatory role for 12-LOX metabolites, such as 12(S)-HETrE, in mediating this It has long been postulated that fatty acid content in the diet can affect human health ( 58 ). Dietary fatty acid formulation has been shown to inhibit leukotriene biosynthesis ( 59 ), and DGLA specifi cally can be converted to the anti-infl ammatory prostaglandin PGE 1 by COX ( 60 ), which is implicated in the inhibition of platelet activation ( 57 ) and in diminishing atherosclerosis ( 61,62 ) and ocular discomfort symptoms ( 63 ). In this study, we have shown a direct antiplatelet phenotype of the 12-LOX product of DGLA, which supports the role of this and potentially other fatty acids as protective agents against unwanted platelet activation and thrombosis.…”

Polyunsaturated fatty acids, hyperlipidemia, and thrombosis.

“…164 ' 165 One human subject fed DHLA had no prolongation of bleeding time. 166 The direct addition of DHLA to platelet-rich plasma does not lead to platelet aggregation and, in fact, may be inhibitory. 165 The mechanism for the putative decrease in platelet reactivity to aggregating agents could reflect decreased thromboxane A 2 production from arachidonic acid by the platelets.…”

The effect of dietary supplementation with linoleic and gammalinolenic acids on the pressor response to angiotensin II‐a possible role in pregnancy‐induced hypertension?

“…A recent report has also shown that the daily ingestion of eight capsules of Efamol, the dose studied in this paper, is associated with a rise in plasma concentration of dihomogammalinolenic acid (Manku et al, 1985). Dietary supplementation with pure gammalinolenic acid increases the capacity of platelets to synthesise prostaglandin E1, and, to a lesser extent, prostaglandin E2, and is associated with potentially antithrombotic changes in haemostatic function (Kernoff et al, 1977 (Broughton Pipkin et al, 1982a,b, 1984. Indeed, the threshold for diastolic pressor response to AII after supplementation was very close to that seen during the infusion of prostaglandin E2 92.95 0.24 compared with 2.99 ± 0.22 ng kg-min-1) and, not significantly lower than the thresholds with prostaglandin El, and epoprostenol of 3.51 ± 0.51 and 3.87 ± 0.81 ng kg~1 min-' respectively.…”