The synergistic effects of ro-3 and ro-6 fatty acids and drugs used in the treatment of Crohn's disease have been reported.6566 Amino-salicylic acid (5-ASA) therapy with ro-3 fatty acids supplementation in the treatment of pediatric patients with Crohn's disease delayed the relapse of episodes. The synergistic effect of the drug and supplement were observed by 5-ASA inhibition of factors of the inflammatory cascade [cyclooxygenase, thromboxane-synthetase, and platelet activating factor (PAF) synthetase], production of IL-1 and free radicals, antioxidant activity, and ro-3 fatty acid inhibition of the PAF synthetase.65 Omega-3 but not ro-6 fatty acids have shown immunomodulatory properties and an increase in pro-inflamatory cytokines in patients receiving enteral ro-3 and ro-6 fatty acids used as adjuvant therapy to corticosteroid medication for the treatment of Crohn's disease.66 Omega-3 fatty acids have been shown to decrease the nephrotoxicity caused by cyclosporine therapy used to prevent rejection in organ transplantation.6768 Female rats fed with a mixture of ro-3 and ro-6 fatty acids and receiving intraperitoneal cyclosporine treatment showed that the metabolites of arachidonic acid increased the levels of thromboxane A, which plays a role in cyclosporine nephrotoxicity. Additionally, the polyunsaturated fatty acid mixture improved prostaglandin synthesis, which plays a beneficial role in the prevention of renal dysfunction.67 It has also been reported that the interaction of ro-3 fatty acids supplementation to patients early after kidney graft as an adjunctive treatment to immunosuppressive regimen with cyclosporine reduces the nephrotoxic effects of this drug.68
Omega-3 fatty acids may increase the risk of bleeding when taken with drugs that increase the risk of bleeding, including aspirin, anticoagulants such as warfarin or heparin, antiplatelet drugs such as clopidogrel, and nonsteroidal anti-inflammatory drugs such as ibuprofen or naproxen.38 A reported case of 1000 to 2000 mg/day intake of fish oil with warfarin medication indicated increased anticoagulation, and the ro-3 fatty acid in the oil may have affected platelet aggregation or vitamin K-dependent coagulation factors, and lowered thromboxane and decreased factor VII concentrations.69 In contrast, there was no effect on vitamin K-dependent coagulation factors, but lowered platelet integrin activation and plasma levels of fibrinogen factor V have been reported with an intake of 3 g of ro-3 fatty acids daily for 4 weeks.
Omega-3 fatty acids supplementation may lower blood pressure by their anti-hypertensive and hypotriglyceridemic effects, and add to the effects of drugs that may also affect blood pressure, such as beta-blockers or diuretics.3870
Omega-3 fatty acids lower triglyceride concentrations and may have a synergistc effect with the triglyceride-lowering effects of agents such as niacin, fibrates such as gemfibrozil, or resins such as cholestyramine. However, ro-3 fatty acids may work against the low-density lipoprotein (LDL) cholesterol-lowering properties of statin drugs.49
Modulation of interleukins by ro-3 fatty acid and intakes of 500 IU of vitamin E in the diet have been reported. These two nutrients may modulate the levels of IL-6, IL-10, IL-12, and tumor necrosis factor-a (TNF-a) in mice.71 Omega-3 fatty acids have been reported to increase the risk of bleeding with the use of Ginkgo biloba, garlic, and saw palmetto; add to the effects of agents that may also affect blood pressure, such as eucalyptol, eucalyptus oil, flaxseed/flaxseed oil, garlic, ginger, and ginkgo, among others; and enhance lower blood sugar properties of aloe vera, American ginseng, bilberry, bitter melon, maitake mushroom, marshmallow, milk thistle, Panax ginseng, rosemary, shark cartilage, and Siberian ginseng, among others.38 Omega-3 fatty acids can increase LDL cholesterol concentrations and may work against the potential LDL-lowering properties of agents like barley, garlic, guggul, psyllium, soy, or sweet almond.38
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