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
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
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
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
The primary uses of omega-3 oils include the following.
- Cardiovascular disease: reducing cholesterol levels and lowering blood
- Allergic and inflammatory conditions, including psoriasis and
- Autoimmune diseases, including multiple sclerosis, lupus, and
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.
|Dosage Ranges and Duration of
- 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
- 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
- A healthy person eating a typical diet should reduce consumption of
saturated fats and increase consumption of the polyunsaturated essential fatty
Excessive amounts of omega-3 oils may reduce blood-clotting
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
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
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
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.
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.
Anti-inflammatory Drugs (NSAIDs)
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.
Al-Harbi MM, Islam MW, Al-Shabanah OA, Al-Gharably NM. Effect of Acute
Administration of Fish Oil (Omega-3 Marine Triglyceride) on Gastric Ulceration
and Secretion Induced by Various Ulcerogenic and Necrotizing Agents in Rats.
Fed Chem. Toxic. 1995;33(7):555-558.
Ando H, Ryu A, Hashimoto A, Oka M, Ichihashi M. Linoleic acid and
alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin.
Arch Dermatol Res. July 1998;290(7):375-381.
Andreassen AK, Hartmann A, Offstad J, Geiran O, Kvernebo K, Simonsen S.
Hypertension prophylaxis with omega-3 fatty acids in heart transplant
recipients. J Am Coll Cardiol 1997;29:1324-1331.
Badalamenti S, Salerno F, Lorenzano E, et al. Renal Effects of Dietary
Supplementation With Fish Oil in Cyclosporine-Treated Liver Transplant Patients.
Billeaud C, Bougle D, Sarda P, et al. Effects of preterm infant formula
supplementation with alpha-linolenic acid with a linoleate/alpha-linoleate
ration of 6. Eur J Clin Nutr. 1997;51(8):520-527.
Danno K, Sugie N. Combination therapy with low-dose etretinate and
eicosapentaenoic acid for psoriasis vulgaris. J Dermatol.
DeDeckere EA, Korver O, Verschuren PM, Katan MB. Health aspects of fish and
n-3 polyunsaturated fatty acids from plant and marine origin. Eur J Clin
Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid
levels in the diet and in red blood cell membranes of depressed patients. J
Affect Disord. 1998;48(2-3):149-155.
Ensminger AH, Ensminger ME, Konlande JE, Robson JRK. Foods & Nutrition
Encyclopedia. 2nd ed. Vol 2. Boca Raton, Fla: CRC Press, Inc;
Garrison RH Jr, Somer E. The Nutrition Desk Reference. 3rd ed. New
Canaan, Conn: Keats Publishing, Inc; 1995:23-64.
Haas EM. Staying Healthy with Nutrition. Berkley, Calif: Celestial
Arts Publishing; 1992:65-79.
Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J
Clin Nutr. 1997;65(5):1645S (10).
Haw M, Linnebjerg H, Chavali SR, Forse RA. The effect of dietary
polyunsaturated fatty acids (PUFA) on acute rejection and cardiac allograft
blood flow in rats. Transplantation. 1995;60(6):570-577.
Homan van der Heide JJ, Bilo HJ, Tegzess AM, Donker AJ. The effects of
dietary supplementation with fish oil on renal function in cyclosporine-treated
renal transplant recipients. Transplantation. 1990;49:523-527.
Iacoviello K, Amore C, De Curtis A, et al. Modulation of fibrinolytic
response to venous occlusion in humans by a combination of low-dose aspirin and
n-3 polyunsaturated fatty acids. Arterioscler Thromb
Kooijmans-Coutinho MF, Rischen-Vos J, Hermans J, Arndt JW, van der Woude FJ.
Dietary fish oil in renal transplant recipients treated with cyclsporin-A: no
beneficial effects shown. J Am Soc Nephrol. 1996;7(3):513-518.
Murray MT. Encyclopedia of Nutritional Supplements. Rocklin, Calif:
Prima Publishing; 1996:239-278.
Murray MT, Pizzorno JE. Encyclopedia of Natural Medicine. 2nd ed.
Rocklin, Calif: Prima Publishing; 1996:49-52, 255, 266, 487, 533-34, 765-66,
Nestel PJ, Pomeroy SE, Sasahara T, et al. Arterial compliance in obese
subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite
increased LDL oxidizability. Arterioscler Thromb Vasc Biol. July
Newstrom H. Nutrients Catalog. Jefferson, NC: McFarland & Co.,
Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and
Disease. 9th ed. Baltimore, Md: Williams & Wilkins; 1999:90-92,
Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar
disorder: a preliminary double-blind placebo-controlled trial. Arch Gen
Ventura HO, Milani RV, Lavie CJ, Smart FW, Stapleton DD, Toups TS, Price HL.
Cyclosporine induced hypertension. Efficacy of omega-3 fatty acids in patients
after cardiac transplantation. Circ. 1993;88(5 Pt 2):II281-285.
Von Schacky C, Angerer P, Kothny W, et al. The effect of dietary omega-3
fatty acids on coronary atherosclerosis. A randomized, double-blind,
placebo-controlled trial. Ann Intern Med. 1999;107(7):554-562.
Voskuil DW, Feskens EJM, Katan MB, Kromhout D. Intake and sources of
alpha-linolenic acid in Dutch elderly men. Euro J Clin Nutr.
Wagner W, Nootbaar-Wagner U. Prophylactic treatment of migraine with
gamma-linolenic and alpha-linolenic acids. Cephalalgia.
Werbach MR. Nutritional Influences on Illness. 2nd ed. Tarzana, Calif:
Third Line Press; 1993:13-22, 655-671.
Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI. Fatty acids and brain
Copyright © 2007 Drugs Area
This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein.