The omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These are long-chain, polyunsaturated fatty acids. Omega-3 fatty acids have been established as essential for optimum tissue formation. Intense research is studying the optimum amounts of omega-3 fatty acids in the diet and their role in the central nervous system.

ALA is found in plant products; EPA and DHA are obtained from fish oils. Additionally, ALA is converted in the human body to EPA and DHA. ALA is found in unhydrogenated oils, such as rapeseed (canola), flaxseed, and soybean oil, and in margarines and other fats containing such oils. Note that many commercial margarines contain high amounts of trans-fatty acids, which probably outweigh the beneficial effects of the omega-3 oils they contain. EPA and DHA can be introduced into the body directly from cold-water fish such as salmon, mackerel, halibut, and herring.

The beneficial effects of the omega-3 series oils include: lowering cholesterol and triglyceride levels, reducing the risk of heart disease, lowering blood pressure, improving rheumatoid arthritis, and protecting myelin formation and function. There is evidence to suggest that omega-3 oils can be helpful in treating asthma, glaucoma, multiple sclerosis, and diabetes, and in preventing cancer.

Recent research indicates that ALA may have a beneficial effect on coronary heart disease, including the inhibition of atherosclerosis. In one small study of 15 obese persons on daily intakes of 20 g of ALA from margarine products based on flaxseed oil, there was improvement in arterial compliance and thus decreased cardiovascular risk, despite a rise in LDL oxidizability. At the same time, insulin sensitivity and HDL cholesterol diminished.

Another study found that the omega-3 fatty acids, whether ALA supplements from vegetable oil or EPA and DHA supplements from marine sources, have largely parallel effects on hemostatic factors.

Other research has indicated that ALA acts equivalently to n-6 fatty acids with respect to lipid and lipoprotein effects, but that very large amounts of ALA, which is plant-based, is needed to have the effect of reducing tricylglycerol concentrations, which is the hallmark effect of the marine-based omega-3 fatty acids. The study concludes that in terms of effects on lipoprotein metabolism, the plant-derived ALA is not equivalent to the marine-based acids. One area of general agreement is that the interrelationship among the fatty acids and the ratio of ALA to linoleic acid in the diet is an important area for further study.

The omega-3 fatty acids have anti-inflammatory and immunoregulatory effects. Successful treatment of migraines and alleviation of depression with omega-3 fatty acids have been reported. A recent study demonstrated that omega-3 fatty acids improved the short-term course of illness in patients with bipolar disorder. One study showed that patients with panic attacks or a history of agoraphobia may benefit from ALA supplementation.

ALA: flax seeds, flaxseed oil, linseed oil, rapeseed oil, canola oil, soybean oil, pumpkin, and walnuts

EPA and DHA: fish oils, particularly from cold-water fish such as salmon, mackerel, halibut, and herring

The parent fatty acid in the omega-3 series, alpha-linolenic acid (ALA), is converted to eicosapentaenoic acid (EPA), then to docosahexaenoic acid (DHA), then to the prostaglandin E₃ series (PGE₃). Marine products can introduce EPA and DHA directly into the body.

The essential fatty acids are vitamin F, yet the Food and Drug Administration prohibits the term "vitamin F" for advertising purposes, because of problems with foods such as french fries being advertised as "vitamin enriched" because they were fried in oil.

There are essentially two types of commercial preparations:

• Cooking oils (canola, soybean, and margarines made from these oils; hydrogenated products are not preferred)
• Medicinal oil (flaxseed)

Several manufacturing methods can destroy the nutrient value of the products. Some preferred methods use proprietary names for their process, generically known as modified atmospheric packing methods. Bio-Electron Process, Spectra-Vac, and Omegaflo are some examples. Generally, a high-quality oil will be certified as organic by a reputable third party, will be found in light-resistant containers, may be refrigerated, and will be dated. These oils have been extracted by expeller presses at relatively low temperatures.

The primary uses of omega-3 oils include the following.

• Cardiovascular disease: reducing cholesterol levels and lowering blood pressure
• Allergic and inflammatory conditions, including psoriasis and eczema
• Autoimmune diseases, including multiple sclerosis, lupus, and cancer

Health conditions that may reflect deficiencies in, or which can be improved by supplementation of, omega-3 oils include: acne, AIDS, allergies, Alzheimer's, angina, arthritis, atherosclerosis, autoimmune diseases, behavioral disorders, breast cysts, breast pain, breast tenderness, cancer, cartilage destruction, coronary bypass, cystic fibrosis, dementia, diabetes, E. coli infection, eczema, heart disease, hyperactivity, hypertension, hypoxia, ichthyosis, immune disorders, infant nutrition, inflammatory conditions, intestinal disorders, kidney function, learning, leprosy, leukemia, lupus, mastalgia, menopause, mental illness, metastasis, multiple sclerosis, myopathy neurological diseases, obesity, osteoarthritis, postviral fatigue, pregnancy malnutrition, psoriasis, Refsum's syndrome, Reye's syndrome, rheumatoid arthritis, schizophrenia, sepsis, Sjogren-Larsson syndrome, stroke, vascular disease, vision.

• There is no Recommended Dietary Allowance (RDA), yet one or two tablespoons of flaxseed oil daily (or equivalent capsule) is considered optimal for a healthy individual. Capsule doses are 3,000 mg per day for prevention and 6,000 mg per day for treatment.
• A diet that gets 1% to 2% of its calories from linoleic acid has been shown to give maximum tissue levels of DHA, avoiding any apparent deficiency symptoms.
• For rheumatoid arthritis, the estimated therapeutic dose of ALA is 5 g/day, while the estimated therapeutic dose of EPA is 1.8 g/day.
• For agoraphobia: 2 to 6 tablespoons of flaxseed oil daily, in divided doses.
• A healthy person eating a typical diet should reduce consumption of saturated fats and increase consumption of the polyunsaturated essential fatty acids.

Excessive amounts of omega-3 oils may reduce blood-clotting time.

Total fat intake should be considered. The ratio of omega-3 fatty acids to other essential fatty acids may be important in treating some conditions, and the balance of omega-3 to omega-6 oils is essential to the metabolism of prostaglandins. Omega-3 oils should be used with caution in patients who bruise easily, have bleeding disorders, or are on blood-thinning medication.

In a double-blind, randomized, cross over study with six healthy volunteers, the combination of aspirin (40 mg/day) and omega-3 fatty acids (5.3 g) decreased fibrinolytic response to venous occlusion (Iacoviello et al. 1992). The combination could be helpful in the treatment of some forms of coronary artery disease.

Rats receiving cardiac allografts that were fed a diet high in omega-3 polyunsaturated fatty acids had a significantly prolonged median graft survival rate (12 days) compared to animals fed either lab chow or a diet high in monounsaturated fatty acids and saturated fat (Haw et al. 1995). When the rats were treated with cyclosporine, myocardial blood flow was greatest in the omega-3 group. Omega-3 fatty acids also exhibited immunosuppressive effects because lymphocyte responses were suppressed to a greater extent in animals treated with these fatty acids.

In a double-blind, randomized, placebo-controlled study with 30 patients, treatment with alpha-tocopherol (3.7 mg); an immunosuppressive regimen consisting of cyclosporine (6 mg/kg body weight), azathioprine (2mg/kg/day), and prednisolone (0.2 mg/kg/day); and omega-3 fatty acids (4 g/day: 46.5% eicosapentaenoic acid (EPA) and 37.8% docosahexaenoic acid (DHA)) decreased systolic pressure and increased diastolic pressure after 6 months (Andreassen et al. 1997). An earlier study involving 20 cardiac transplant patients who received omega-3 fatty acids (3 g/day: 1500 mg each EPA and DHA) with cyclosporine and antihypertensive medications for 12 weeks supports these findings (Ventura et al. 1993). The mechanism for the interaction between cyclosporine and omega-3 fatty acids may be decreased systemic vascular resistance. Prophylactic administration of a combination of omega-3 fatty acids and cyclosporine may effectively control hypertension in cardiac transplant patients.

Another placebo-controlled, prospective, double-blind, randomized study involving 26 liver transplant patients evaluated the effects of omega-3 fatty acids (12 g/day: 18% EPA and 12% DHA) on cyclosporine-induced nephrotoxicity (Badalamenti et al. 1995). After 2 months, renal plasma flow increased by 22%, the glomerular filtration rate (GFR) increased by 33%, renal blood flow increased by 17%, and renal vascular resistance decreased by 20%. Kidney transplant recipients also benefited from supplementation with omega-3 fatty acids (6 g: 30% EPA and 20% DHA) during cyclosporine therapy in a double-blind, placebo-controlled, prospective, randomized clinical trial involving 24 subjects (Homan van der Heide et al. 1990). After 3 months, blood pressure decreased, and GFR and renal plasma flow increased by 20.3% and 16.4%, respectively. However, another double-blind, randomized, controlled study found that 25 renal transplant patients did not derive clinically significant benefits after one year of treatment with omega-3 fatty acids (6 g) (Kooijmans-Coutinho et al. 1996).

A randomized, open study evaluated the effects of highly-purified eicosapentaenoic acid (1800 mg/day) combined with low-dose etretinate (0.3 to 0.5 mg/kg/day) for 12 weeks in patients with chronic, stable psoriasis vulgaris (Danno and Sugie 1998). Patients continued to be treated with a topical corticosteroid that had previously been ineffective. Clinical improvement was noted in all patients receiving etretinate with EPA, whereas only 90% of patients responded to etretinate monotherapy. Reports of adverse events were similar for both groups.

Omega-3 fatty acids (5 and 10 mL/kg) significantly protected the gastric mucosa against ulcerative agents, including NSAIDs, in rats (Al-Harbi et al. 1995).

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