Anticlotting

There has been a surprising number of studies investigating the influence of ALA from FSO on coagulation and fibrinolysis, and enormous variation in results. Methodological issues have plagued the overall quality of evidence, with small sample sizes, inconsistent methodologies and diverse sample characteristics making interpretation difficult.

One early study compared different dietary ratios of n-6 and n-3 EFAs in relation to prostanoid production in a group of normolipidaemic men (Kelley et al 1993). The high ALA dietary intervention constituted an overall n-6:n-3 ratio of 2.7 versus control ratios of up to 27.4. Following the 18 days of the intervention, groups showed significant differences in measured outcomes, notably, that 6-keto-PGFi_a|pha was significantly higher following the high ALA diet but no evidence of significant effect on bleeding time or thromboxane B2 production. A second study published in the same year also failed to show an effect on clotting; however, the dose of FSO used was only 4.3 g/day (Kelley et al 1993). In contrast, the results of a study using a much larger dose of 40 g/day of FSO over 23 days in 11 healthy men showed that FSO significantly reduced collagen-induced aggregation response when compared to 40 g/day sunflower seed oil (Allman et al 1995).

A follow-up study of 29 healthy males that was conducted over 6 weeks investigated the effects of a diet in which approximately 7% of the total kilocalories from polyunsaturated fat was made up of either an ALA-rich (n-3:n-6 = 1:1.2) or LA-rich diet (n-3:n-6 = 1:21). The ALA-enriched diet resulted in triple the EPA phospholipid levels compared to the LA-enriched diet, but had no demonstrable effect on coagulation or fibrinolysis, other than an increase in the ratio of activated protein C. The authors speculated that the latter finding may still prove significant, but suggest that future studies should be conducted in patients with vascular pathology, as healthy clotting profiles may have obscured the true effects of FSO (Allman-Farinelli etal 1999).

In the same year another group of Australian researchers published the results of their study of 17 vegetarian men who were assigned to either a low- or high-ALA diet (derived from FSO) for 28 days following a run-in baseline diet for 14 days. Again there were no significant differences in prothrombin time, activated partial thromboplastin time, or plasminogen activities with the different ALA diets, despite increases in EPA and DPA levels (Li et al 1999).

Since 1994 Mutanen and Freese have conducted many studies assessing the effect of ALA and LA:ALA ratios on haemostatic factors (Freese & Mutanen 1997, Freese et al 1994, Mutanen & Freese 2001). Their 1997 study was the largest and involved a

sample of 46 subjects who were given FSO to provide 5.9 g/day ALA or a fish/sunflower oil combination equal to 5.2 g/day EPA/DHA over 4 weeks. Extensive analysis of the sample throughout the intervention, as well as at the 12-week follow-up, revealed no difference in collagen-induced platelet aggregation, thromboxane production or bleeding time between the two groups, suggesting equivalent anticoagulant effects for FSO and fish oil when consumed in comparable quantities This was despite smaller increases in EPA levels in the platelets of the subjects taking FSO.

The largest and most recent trial (Finnegan et al 2003) compared the effects of small increases in ALA (4.5 or 9.5 g/day) and EPA and DHA (0.8 or 1.7 g/day EPA+DHA) intake on blood coagulation and fibrinolytic factors over 6 months. The randomised, placebo-controlled, parallel study of 1 50 moderately hyperlipidaemic subjects found no significant differences in coagulation or fibrinolysis for any intervention.

Currently the evidence is equivocal, but may indicate a minor anti-aggregatory role for FSO in high doses. Further research, with more heterogeneous designs, is required to form any valid conclusion.

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