Current references advise caution with concurrent use of OEP and several classes of medications (anticoagulants, antipsychotics/anticonvulsants) because of possible serious side effects (53-55).

The use of anticonvulsants and OEP may result in a delayed reduction in the effectiveness of the anticonvulsant because OEP may lower the seizure threshold (56,57). In 1981, three patients on phenothiazine therapy for schizophrenia were given OEP (around this time, OEP was being considered a possible adjunct to therapy for this mental illness). The patients suffered seizures, OEP was discontinued, and electroencephalograms were performed. The tests showed temporal lobe epileptic disorders and phenothiazine therapy was discontinued or reduced in the patients and carbamazepine started. The authors suggested that OEP supplementation be used with caution in patients taking phenothiazines (58). In 1983, Holman et al. reported an incident involving a 43-year old man with schizophrenia on fluphenazine decanoate therapy who suffered a grand mal seizure after using 4 g of OEP daily for 3 months. Once the OEP was discontinued, no seizures occurred in the next 7 months (28).

The use of OEP with antiplatelets, thrombolytics, low-molecular-weight heparins, or anticoagulants may result in a delayed but increased risk of bleeding, and concomitant use is not advised (54,59). The mechanism of action is theorized to be decreased thromboxane B2 synthesis and increased prostacyclin production caused by y-linolenic acid, resulting in inhibition of platelet aggregation and prolonged bleeding time (42).

In vitro experiments by Zou et al. in 2002 examined the effect of the cis-linoleic acid component of OEP on the catalytic activity of cDNA-expressed cytochrome P450 isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). The highest concentration of cis-linoleic acid tested was 179 |M. In these assays, inhibitory concentration of 50% (IC50) values no greater than 10 |M were considered potent inhibitors and IC50 values between 10 and 50 |M were labeled moderate inhibitors. cis-Linoleic acid tested as a moderate inhibitor of all the cDNA-derived enzymes except CYP3A4 (resorufin benzyl ether substrate) (60). However, there have been no case reports of toxicity or adverse reactions with OEP and drugs metabolized by this enzyme.

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