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Omega-6

Omega-6 is a type of polyunsaturated fat that lowers LDL cholesterol. Eating foods with unsaturated fat, including omega-6, instead of foods high saturated and trans fats helps to get the right balance for your blood cholesterol (lower LDL and increase HDL).

 

Overview

Omega-6 fatty acids are essential fatty acids. They are necessary for human health, but the body cannot make them. You have to get them through food. Along with omega-3 fatty acids, omega-6 fatty acids play a crucial role in brain function, and normal growth and development. As a type of polyunsaturated fatty acid (PUFA), omega-6s help stimulate skin and hair growth, maintain bone health, regulate metabolism, and maintain the reproductive system.

A healthy diet contains a balance of omega-3 and omega-6 fatty acids. Omega-3 fatty acids help reduce inflammation, and some omega-6 fatty acids tend to promote inflammation. In fact, some studies suggest that elevated intakes of omega-6 fatty acids may play a role in complex regional pain syndrome. The typical American diet tends to contain 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids.

The Mediterranean diet, on the other hand, has a healthier balance between omega-3 and omega-6 fatty acids. Studies show that people who follow a Mediterranean-style diet are less likely to develop heart disease. The Mediterranean diet does not include much meat (which is high in omega-6 fatty acids, though grass fed beef has a more favorable omega-3 to omega-6 fatty acid ratio), and emphasizes foods rich in omega-3 fatty acids, including whole grains, fresh fruits and vegetables, fish, olive oil, garlic, as well as moderate wine consumption.

There are several different types of omega-6 fatty acids, and not all promote inflammation. Most omega-6 fatty acids in the diet come from vegetable oils, such as linoleic acid (LA), not to be confused with alfa-linolenic acid (ALA), which is an omega-3 fatty acid. Linoleic acid is converted to gamma-linolenic acid (GLA) in the body. It can then break down further to arachidonic acid (AA). GLA is found in several plant-based oils, including evening primrose oil (EPO), borage oil, and black currant seed oil.

GLA may actually reduce inflammation. Much of the GLA taken as a supplement is converted to a substance called DGLA that fights inflammation. Having enough of certain nutrients in the body (including magnesium, zinc, and vitamins C, B3, and B6) helps promote the conversion of GLA to DGLA.

Uses

Omega-6 fatty acids may be useful for the following health conditions:

Diabetic neuropathy

Some studies show that taking gamma linolenic acid (GLA) for 6 months or more may reduce symptoms of nerve pain in people with diabetic neuropathy. People who have good blood sugar control may find GLA more effective than those with poor blood sugar control.

Rheumatoid arthritis (RA)

Studies are mixed as to whether evening primrose oil (EPO) helps reduce symptoms of RA. Preliminary evidence suggests EPO may reduce pain, swelling, and morning stiffness, but other studies have found no effect. When using GLA for symptoms of arthritis, it may take 1 to 3 months for benefits to appear. It is unlikely that EPO would help stop progression of the disease. So joint damage would still occur.

Allergies

Omega-6 fatty acids from food or supplements, such as GLA from EPO or other sources, have a longstanding history of folk use for allergies. Women who are prone to allergies appear to have lower levels of GLA in breast milk and blood. However, there is no good scientific evidence that taking GLA helps reduce allergy symptoms. Well-conducted research studies are needed.

Before you try GLA for allergies, work with your doctor to determine if it is safe for you. Then follow your allergy symptoms closely for any signs of improvement.

Attention deficit/hyperactivity disorder (ADHD)

Clinical studies suggest that children with ADHD have lower levels of EFAs, both omega-6s and omega-3s. EFAs are important to normal brain and behavioral function. Some studies indicate that taking fish oil (containing omega-3 fatty acids) may help reduce ADHD symptoms, though the studies have not been well designed. Most studies that used EPO have found it was no better than placebo at reducing symptoms.

Breast cancer

One study found that women with breast cancer who took GLA had a better response to tamoxifen (a drug used to treat estrogen-sensitive breast cancer) than those who took only tamoxifen. Other studies suggest that GLA inhibits tumor activity among breast cancer cell lines. There is some research suggesting that a diet rich in omega-6 fatty acids may promote breast cancer development. DO NOT add fatty acid supplements, or any supplements, to your breast cancer treatment regimen without your doctor's approval.

Eczema

Evidence is mixed as to whether EPO can help reduce symptoms of eczema. Preliminary studies showed some benefit, but they were not well designed. Later studies that examined people who took EPO for 16 to 24 weeks found no improvement in symptoms. If you want to try EPO, talk to your doctor about whether it is safe for you.

High blood pressure (hypertension)

Preliminary evidence suggests that GLA may help reduce high blood pressure, either alone or in combination with omega-3 fatty acids found in fish oil, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In one study, men with borderline high blood pressure who took 6g of blackcurrant oil had a reduction in diastolic blood pressure compared to those who took placebo.

Another study examined people with intermittent claudication, which is pain in the legs while walking that is caused by blockages in the blood vessels. Those who took GLA combined with EPA had a reduction in systolic blood pressure compared to those who took placebo.

More research is needed to see whether GLA is truly effective for hypertension.

Menopausal symptoms

EPO has gained popularity as a way to treat hot flashes associated with menopause. But so far studies have been inconclusive. If you want to try EPO for hot flashes and night sweats, ask your doctor whether it is safe and right for you.

Breast pain (mastalgia)

Some evidence suggests that EPO may reduce breast pain and tenderness in people with cyclic mastalgia. It may also help reduce symptoms to a lesser extent in people with noncyclic mastalgia. However, it does not seem to be effective for severe breast pain.

Multiple sclerosis (MS)

EPO has been suggested as an additional treatment (along with standard therapy) for MS, although there is no scientific evidence that it works. People with MS who want to add EPO to their treatment regimens should talk with a health care provider.

Osteoporosis

Some studies suggest that people who do not get enough essential fatty acids (particularly EPA and GLA) are more likely to have bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those who took EPA and GLA supplements had less bone loss over 3 years than those who took placebo. Many of these women also experienced an increase in bone density.

Premenstrual syndrome (PMS)

Although most studies have found no effect, some women report relief of PMS symptoms when using GLA. The symptoms that seem to improve the most are breast tenderness and feelings of depression, as well as irritability and swelling and bloating from fluid retention.

Dietary Sources

For general health, there should be a balance between omega-6 and omega-3 fatty acids. The ratio should be in the range of 2:1 to 4:1, omega-6 to omega-3, and some health educators advocate even lower ratios. Omega-6 fatty acids can be found in sunflower, safflower, soy, sesame, and corn oils. The average diet provides plenty of omega-6 fatty acids, so supplements are usually not necessary. People with specific conditions, such as eczema, psoriasis, arthritis, diabetes, or breast tenderness (mastalgia) may want to ask their doctors about taking omega-6 supplements.

Available Forms

Omega-6 fatty acids are available in supplemental oils that contain linoleic acid (LA) and GLA, such as EPO (Oenothera biennis) and black currant (Ribes nigrum) oils. Spirulina (often called blue-green algae) also contains GLA.

How to Take It

The average diet provides sufficient omega-6 fatty acids, so supplementation is usually not necessary unless you are treating a specific condition, such as:

  • Eczema
  • Psoriasis
  • Arthritis
  • Diabetes
  • Breast tenderness (mastalgia)

The dose and form of omega-6 fatty acids to be supplemented depends on many factors, including:

  • The condition being treated
  • Age
  • Weight
  • Other medications and supplements being used

Speak to your doctor to determine what form and what dose of omega-6 fatty acids are most appropriate for you.

Precautions

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

DO NOT take omega-6 fatty acids if you have a seizure disorder because there have been reports of these supplements causing seizures. Several reports describe seizures in people taking EPO. Some of these seizures developed in people with a previous seizure disorder, or in people taking EPO in combination with anesthetics. People who plan to undergo surgery requiring anesthesia should stop taking EPO 2 weeks ahead of time.

Borage seed oil, and possibly other sources of GLA, should not be taken during pregnancy because they may harm the fetus and induce early labor.

Avoid doses of GLA greater than 3,000 mg per day. At that level, an increase in inflammation may occur.

Side effects of EPO can include occasional headache, abdominal pain, nausea, and loose stools. In animal studies, GLA is reported to decrease blood pressure. Early results in human studies do not show consistent changes in blood pressure.

Laboratory studies suggest that omega-6 fatty acids, such as the fats found in corn oil, promote the growth of prostate tumor cells. Until more research is done, health professionals recommend not taking omega-6 fatty acids, including GLA, if you are at risk of or have prostate cancer.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use omega-6 supplements without talking to your health care provider first.

Blood-thinning medications: People taking blood thinners, including warfarin (Coumadin) or clopidogrel (Plavix), should not take omega-6 fatty acid supplements without a doctor's supervision. Omega-6 and omega-3 fatty acids may increase the risk of bleeding.

Ceftazidime: GLA may increase the effectiveness of ceftazidime. Ceftazidime, an antibiotic, is used against a variety of bacterial infections.

Chemotherapy for cancer: GLA may increase the effects of anti-cancer treatments, such as doxorubicin, cisplatin, carboplatin, idarubicin, mitoxantrone, tamoxifen, vincristine, and vinblastine.

Cyclosporine: Cyclosporine is a medication used to suppress the immune system after organ transplantation. Taking omega-6 fatty acids with cyclosporine may increase the immunosuppressive effects of this medication. It may also protect against kidney damage, which is a potential side effect from cyclosporine.

Phenothiazines: People taking a class of medications called phenothiazines to treat schizophrenia should not take EPO. EPO may interact with these medications and increase the risk of seizures. The same may be true for other omega-6 supplements. These medications include:

  • Chlorpromazine (Thorazine)
  • Fluphenazine (Stelazine)
  • Perphenazine (Trilafon)
  • Promethazine (Compazine)
  • Thioridazine (Mellaril)

Supporting Research

Allen KL, Mori TA, Beilin L, Byrne SM, Hickling S, Oddy WH. Dietary intake in population-based adolescents: support for a relationship between eating disorder symptoms, low fatty acid intake and depressive symptoms. J Hum Nutr Diet. 2013;26(5):459-69.

Anandan C, Nurmatov U, Sheikh A. Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis.Allergy. 2009 Jun;64(6):840-8. Epub 2009 Apr 7.

Attar-Bashi NM, Li D, Sinclair AJ. alfa-linolenic acid and the risk of prostate cancer. Lipids. 2004;39(9):929-32.

de Lorgeril M, Salen P. New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids.BMC Med. 2012;10:50.

De Spirt S, Stahl W, Tronnier H, Sies H, Bejot M, Maurette JM, Heinrich U. Intervention with flaxseed and borage oil supplements modulates skin condition in women. Br J Nutr. 2009 Feb;101(3):440-5.

Freeman VL, Meydani M, Hur K, Flanigan RC. Inverse association between prostatic polyunsaturated fatty acid and risk of locally advanced prostate carcinoma. Cancer. 2004;101(12):2744-54.

Geppert J, Demmelmair H, Hornstra G, Koletzko B. Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations. Br J Nutr. 2008 Feb;99(2):360-9.

Harris W. Omega-6 and omega-3 fatty acids: partners in prevention.Curr Opin Clin Nutr Metab Care. 2010;13(2):125-9.

Kankaanpaa P, Nurmela K, Erkkila A, et al. Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fattty acids of infants in relation to atopy. Allergy. 2001;56(7):633-638.

Kast RE. Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alfa. Int Immunopharmacol. 2001;1(12):2197-2199.

Kenny FS, Pinder SE, Ellis IO et al. Gamma linolenic acid with tamoxifen as primary therapy tn breast cancer. Int J Cancer. 2000;85:643-648.

Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr. 2000;71(1 Suppl):179S-188S.

Kupferer EM, Dormire SL, Becker H. Complementary and alternative medicine use for vasomotor symptoms among women who have discontinued hormone therapy. J Obstet Gynecol Neonatal Nurs. 2009 Jan-Feb;38(1):50-9.

Little C, Parsons T. Herbal therapy for treating rheumatoid arthritis.Cochrane Database Syst Rev. 2001;(1):CD002948.

Manjari V, Das UN. Effect of polyunsaturated fatty acids on dexamethasone-induced gastric mucosal damage. Prostaglandins Leukot Essent Fatty Acids. 2000;62(2):85-96.

Menendez JA, del Mar Barbacid M, Montero S, et al. Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Eur J Cancer. 2001;37:402-413.

Rakel D. Integrative Medicine. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.

Ramsden C, Gagnon C, Graciosa J, et al. Do omega-6 and trans fatty acids play a role in complex regional pain syndrome? A pilot study.Pain Med. 2010;11(7):1115-25.

Richardson AJ, Puri BK. The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. 2000;63(1/2):79-87.

Schirmer MA, Phinney SD. Gamma-linolenate reduces weight regain in formerly obese humans. J Nutr. 2007 Jun;137(6):1430-5.

Senapati S, Banerjee S, Gangopadhyay DN. Evening primrose oil is effective in atopic dermatitis: a randomized placebo-controlled trial.Indian J Dermatol Venereol Leprol. 2008 Sep-Oct;74(5):447-52.

Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol. 2011;44(2):203-15.

Srivastava A, Mansel RE, Arvind N, Prasad K, Dhar A, Chabra A. Evidence-based management of Mastalgia: a meta-analysis of randomised trials. Breast. 2007 Oct;16(5):503-12. Epub 2007 May 16.

Sumich AL, Matsudaira T, Heasman B, et al. Fatty acide correlates of temperament in adolescent boys with attention deficit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids. 2013;88(6):431-6.

Surette ME, Stull D, Lindemann J. The impact of a medical food containing gamma-linolenic and eicosapentaenoic acids on asthma management and the quality of life of adult asthma patients. Curr Med Res Opin. 2008 Feb;24(2):559-67.

Townsend. Sabiston Textbook of Surgery. 19th ed. Philadelphia, PA: Elsevier Saunders; 2012.

Vanhala M, Saltevo J, Soininen P, et al. Serum omega-6 polyunsaturated fatty acids and the metabolic syndrome: a longitudinal population-based cohort study. Am J Epidemiol. 2012;176(3):253-60.

Weaver KL, Ivester P, Seeds M, Case LD, Arm JP, Chilton FH. Effect of dietary fatty acids on inflammatory gene expression in healthy humans. J Biol Chem. 2009 Jun 5;284(23):15400-7. Epub 2009 Apr 9.

Wakai K, Okamoto K, Tamakoshi A, Lin Y, Nakayama T, Ohno Y. Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross-sectional study in Japan. Ann Epidemiol. 2001;11(1):59-64.

Worm M, Henz BM. Novel unconventional therapeutic approaches to atopic eczema. Dermatology. 2000;201(3):191-195.

Alternative Names

Evening primrose oil; EPO; Linoleic acid; LA

Version Info

  • Last reviewed on 8/5/2015
  • Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

 

A study published today in the British Medical Journal finds that people who followed health advice and ate certain omega-6 polyunsaturated fats instead of animal fats had higher death rates. This study has prompted media comment as it appears to contradict established health guidance. Polyunsaturated fats are commonly used in "healthy" margarines, spreads and other alternatives to butter.

However, experts say that we should not be unduly alarmed. The Science Media Centre has issued a statement that says that the research, "does not alter our understanding of the possible relationship between diet and cardiovascular risk" and that "the claims in the paper are not new or at odds with existing evidence".

There's a danger of over-interpreting this research. It focused on one, not all, omega-6 polyunsaturated fats, and the results are in a very specific group – middle-aged men who had had heart attacks.

The study suggests that not all polyunsaturated fatty acids are good for the heart. But British consumers should not panic – the safflower oil used as a source of omega-6 in this study is rarely used in this country.

Where did the story come from?

The study was carried out by researchers in the US and Australia. It was funded by the Life Insurance Medical Research Fund of Australia and New Zealand and the Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health.

The study was published in the peer-reviewed British Medical Journal.

What kind of research was this?

This was a second analysis of a randomised controlled trial performed in Australia between 1966 and 1973. A randomised controlled trial is the ideal trial design to examine cause and effect. However, the current analysis includes outcomes that were not primary outcomes of the original trial.  

The original trial investigated whether replacing sources of saturated fats, such as animal fats and butter, with safflower oil (a kind of oil used for cooking and in some manufactured foods) reduced the risk of death from any cause in men with premature coronary heart disease. It only reported the risk of death from all causes and deaths due tocardiovascular disease (CVD) or coronary heart disease (CHD) were not examined.

In this new study, the researchers calculated whether eating more safflower oil affected the risk of death in people with cardiovascular or coronary heart disease (this is called "secondary prevention"). The researchers also wanted to know to what extent an increased intake of polyunsaturated fatty acids or saturated fatty acids was associated with deaths from CVD or CHD. The results of this new analysis were then used to update a meta-analysis of other trials looking at polyunsaturated fatty acids for cardiovascular risk reduction.

What did the research involve?

Researchers recruited 458 men aged between 30 and 59 who had suffered a heart attack or an episode of coronary insufficiency or angina after admission to hospital. These men were randomised to receive either a dietary intervention or no specific dietary instruction, in addition to standard medical care.

The dietary intervention consisted of instructions to:

  • increase polyunsaturated fatty acid intake to about 15% of total energy intake
  • reduce saturated fatty acid intake to less than 10% of energy intake
  • reduce cholesterol to less than 300mg per day

To help achieve these targets, the men were given liquid safflower oil and safflower oil polyunsaturated margarine. They were told to use these items to replace animal fats, butter and margarine, shortenings, cooking oils and salad dressing, as well as taking safflower oil as a supplement. Safflower oil contains 74.6g per 100g of a type of polyunsaturated fat called omega-6 linoleic acid, and no other polyunsaturated fatty acids.

Men returned for clinical assessment every three months for the first year and then every six months for a median of 39 months. Blood samples were taken to measure the levels of cholesterol and triglyceride (fat). The men also filled in a food diary so that their diet could be assessed.

Deaths that occurred during the trial were assigned codes from the International Classification of Diseases (ICD), according to information taken from death certificates of final hospital admission records. Using survival analysis, the researchers analysed whether the risk of death from any cause or deaths from cardiovascular and coronary heart disease differed between the intervention and the control group. The researchers also examined whether nutrient intake (based on the results of the food diaries) accounted for changes in mortality.

What were the basic results?

  • men in the intervention group significantly increased their intake of polyunsaturated fatty acids, and significantly reduced their intake of saturated fatty acids, cholesterol and mono-unsaturated fatty acids compared with the control group
  • the level of cholesterol in the blood decreased significantly more for men in the dietary intervention group compared with the control group, although changes in the level of triglycerides (fats) in the blood, body mass index (BMI) and blood pressure were similar between groups
  • men in the dietary intervention group had higher rates of deaths from any cause than controls (17.6% of the dietary intervention group died compared with 11.8% of the no intervention group, hazard ratio 1.62, 95% confidence interval 1.00 to 2.64)
  • men in the dietary intervention group had higher rates of death from cardiovascular disease (17.2% of the dietary intervention group died due to cardiovascular disease compared with 11.0% of the no intervention group, hazard ratio 1.70, 95% confidence interval 1.03 to 2.80)
  • men in the dietary intervention group had higher rates of deaths from coronary heart disease (16.3% of the dietary intervention group died due to coronary heart disease compared with 10.1% of the no intervention group, hazard ratio 1.74, 95% confidence interval 1.04 to 2.92)
  • an increase in 5% of food energy from omega-6 linoleic acid predicted a 35% higher risk of cardiovascular death and a 29% increase in all-cause mortality in the intervention group

When these results were added to a meta-analysis of other trials that have assessed the effects of linoleic acid, it was found that linoleic acid increased the risk of death from coronary heart disease and cardiovascular disease, although these results were not significant.

How did the researchers interpret the results?

The researchers have concluded that there is no clear clinical evidence that the most common polyunsaturated fatty acid, omega-6 linoleic acid, can reduce people's risk of developing heart conditions. "Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega-6 linoleic acid, have not been established.

"In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit.

"These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats."

Conclusion

Contrary to received wisdom, this research suggests that not all polyunsaturated fatty acids are good for the heart (the so-called "cardioprotective effect").

This study has several strengths. It was a randomised controlled trial, using just one type of oil to increase consumption of polyunsaturated fatty acids.

However, the study also has its limitations. The dietary data collected during the original trial does not contain enough information to rule out the possibility that changes in other nutrients could have caused the effect seen.

In this trial, participants were advised to increase their intake of polyunsaturated fatty acids, mainly from omega 6-linoleic acid, to 15% of total food energy, and the results may not be generalisable to lower linoleic acid intakes.

As this trial was performed on men aged between 30 and 59 who had premature coronary heart disease, it may not be possible to generalise the results to men who do not have coronary heart disease, men of different ages, and women.

It is worth noting that vegetable oils have very different characteristics in terms of the proportions of omega-3 or omega-6 content and the types of polyunsaturated, monounsaturated and saturated fatty acids that they contain. Oleic acid and linoleic acid are likely to have different properties, and so it cannot be assumed any effect seen here is typical of all vegetable oils.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Start spreading the news - saturated fat 'is not so bad,' says study. The Independent, February 5 2013

Heart attack risk in 'healthy spreads'. Daily Express, February 6 2013

Swapping the butter for margarine 'may be
bad for your health'. U.S. scientists claim polyunsaturated fat 'doubles heart risk'
. Daily Mail, February 6 2013

Links to the science

Ramsden CE, Zamora D, Leelarthaepin B, et al.  Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ. Published online February 6 2013

Editorial
Calder PC. Old study sheds new light on the fatty acids and cardiovascular health debate. BMJ. Published online February 5 2013

  • AHA Science Advisory

Omega-6 Fatty Acids and Risk for Cardiovascular Disease

A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention

  1. Frank Sacks, MD, FAHA
Key Words:

A large body of literature suggests that higher intakes of omega-6 (or n-6) polyunsaturated fatty acids (PUFAs) reduce risk for coronary heart disease (CHD). However, for the reasons outlined below, some individuals and groups have recommended substantial reductions in omega-6 PUFA intake.1–4 The purpose of this advisory is to review evidence on the relationship between omega-6 PUFAs and the risk of CHD and cardiovascular disease.

Omega-6 PUFAs

Omega-6 PUFAs are characterized by the presence of at least 2 carbon-carbon double bonds, with the first bond at the sixth carbon from the methyl terminus. Linoleic acid (LA), an 18-carbon fatty acid with 2 double bonds (18:2 omega-6), is the primary dietary omega-6 PUFA. LA cannot be synthesized by humans, and although firm minimum requirements have not been established for healthy adults, estimates derived from studies in infants and hospitalized patients receiving total parenteral nutrition suggest that an LA intake of ≈0.5% to 2% of energy is likely to suffice. After consumption, LA can be desaturated and elongated to form other omega-6 PUFAs such as γ-linolenic and dihomo-γ-linolenic acids. The latter is converted to the metabolically important omega-6 PUFA arachidonic acid (AA; 20:4 omega-6), the substrate for a wide array of reactive oxygenated metabolites. Because LA accounts for 85% to 90% of the dietary omega-6 PUFA, this advisory focuses primarily on this fatty acid, recognizing that dietary AA, which can affect tissue AA levels,5 may have physiological sequelae.6–8 LA comes primarily from vegetable oils (eg, corn, sunflower, safflower, soy). The average US intake of LA, according to National Health and Nutrition Examination Survey 2001 to 2002 data for adults ≥19 years of age, is 14.8 g/d.9 On the basis of an average intake of 2000 kcal/d, LA intake is 6.7% of energy. AA (≈0.15 g/d) is consumed preformed in meat, eggs, and some fish.

Omega-6 PUFAs and Inflammation

Arguments for reduced LA intakes are based on the assumption that because CHD has an inflammatory component10 and because the omega-6 fatty acid, AA, is the substrate for the synthesis of a variety of proinflammatory molecules, reducing LA intakes should reduce tissue AA content, which should reduce the inflammatory potential and therefore lower the risk for CHD. The evidence, derived primarily from human studies, regarding this line of reasoning is examined below.

AA is the substrate for the production of a wide variety of eicosanoids (20-carbon AA metabolites). Some are proinflammatory, vasoconstrictive, and/or proaggregatory, such as prostaglandin E2, thromboxane A2, and leukotriene B4. However, others are antiinflammatory/antiaggregatory, such as prostacyclin, lipoxin A4,11 and epoxyeicosatrienoic acids.12 Epoxyeicosatrienoic acids are fatty acid epoxides produced from AA by a cytochrome P450 epoxygenase. Epoxyeicosatrienoic acids also have important vasodilator properties via hyperpolarization and relaxation of vascular smooth muscle cells.13 Importantly, because the production of AA from LA is tightly regulated,14 wide variations in dietary LA (above minimal essential intakes) do not materially alter tissue AA content.15 In tracer studies, the extent of conversion of LA to AA is ≈0.2%.16

In studies with vascular endothelial cells, omega-6 PUFA had antiinflammatory properties, suppressing the production of adhesion molecules, chemokines, and interleukins, all key mediators of the atherosclerotic process.17 In human studies, higher plasma levels of omega-6 PUFAs, mainly AA, were associated with decreased plasma levels of serum proinflammatory markers, particularly interleukin-6 and interleukin-1 receptor antagonist, and increased levels of antiinflammatory markers, particularly transforming growth factor-β.18 When healthy volunteers were given ≈7 times the usual intake of AA (ie, 1.5 g/d) in a 7-week controlled feeding study, no effects on platelet aggregation, bleeding times, the balance of vasoactive metabolites, serum lipid levels, or immune response were observed.5–8 Likewise, in a recent study from Japan, AA supplementation (840 mg/d for 4 weeks) had no effect on any metabolic parameter or platelet function.19 Consistent with this, in observational studies, higher omega-6 PUFA consumption was associated with unaltered or lower levels of inflammatory markers.20

Diets high in LA can increase the ex vivo susceptibility of low-density lipoprotein (LDL) to oxidation,21 and oxidized LDL can promote vascular inflammation.22 Therefore, oxidized LDL may play some role in the etiology of CHD.23 However, the extent of LDL oxidation at higher LA intakes (5% to 15% of energy) has not been established, and its clinical relevance is in question owing to the general failure of antioxidant treatments to mitigate CHD risk in most randomized trials.24 At present, little direct evidence supports a net proinflammatory, proatherogenic effect of LA in humans.22,25,26

Omega-6 PUFA Consumption and Other CHD Risk Factors/Markers

The cholesterol-lowering effect of LA is well established from human trials. In a meta-analysis of 60 feeding studies including 1672 volunteers, the substitution of PUFA (largely omega-6, varying from 0.6% to 28.8% energy) for carbohydrates had more favorable effects on the ratio of total to high-density lipoprotein cholesterol (perhaps the best lipid predictor of CHD risk) than any class of fatty acids.27 Higher plasma PUFA levels are associated with a reduced ratio of total to high-density lipoprotein cholesterol,28 and epidemiologically, the replacement of 10% of calories from saturated fatty acid with omega-6 PUFA is associated with an 18-mg/dL decrease in LDL cholesterol, greater than that observed with similar replacement with carbohydrate.29 These findings confirm an LDL-lowering effect of omega-6 PUFA beyond that produced by the removal of saturated fatty acids. Favorable effects of LA on cholesterol levels are thus well documented and would predict significant reductions in CHD risk. Additionally, higher LA intakes may improve insulin resistance30 and reduce the incidence of diabetes mellitus,31 and higher serum LA levels are associated with lower blood pressure.32 Nevertheless, not all studies support a beneficial effect of LA on CHD risk markers. For example, an angiographic study reported a direct association between PUFA intakes and luminal narrowing in women with CHD.33 However, effects on markers do not always translate into effects on actual clinical end points; thus, it is essential to evaluate the relations between LA consumption and CHD events.

Omega-6 PUFA Consumption and CHD Events: Observational Studies

Ecological Studies

Cross-cultural, cross-sectional, and time-trend studies examining omega-6 PUFA intake and CHD risk demonstrate equivocal results.34,35 Among the 4584 subjects in the National Heart, Lung, and Blood Institute Family Heart Study, the prevalence of coronary artery disease was ≈66% higher at LA intakes of 1.8% compared with 5.3%.36 The weaknesses of these study designs for evaluating diet-disease relations are well documented,37 and most evaluated only total PUFA intake, failing to distinguish between omega-3 and omega-6 PUFAs and their potentially distinct effects. Given these limitations, firm conclusions cannot be drawn from these studies.

Case-Control Studies

In a meta-analysis of 25 case-control studies (including 1998 cases and 6913 controls) evaluating blood/tissue omega-6 PUFA content and CHD events, LA content was inversely associated with CHD risk, whereas AA was unrelated to CHD risk.38 Even very high LA intakes have been associated with lower risk; in 1 study in Israel,39 where 25% of the population consumes >12% of energy as omega-6 PUFA, an inverse association was found between adipose LA and acute myocardial infarction after controlling for other omega-6 PUFAs.

Prospective Cohort Studies

These observational studies use the strongest designs, minimizing both selection and recall bias. No significant associations between LA or omega-6 PUFA intake and CHD risk were seen in the Finnish alfa-Tocopherol, Beta-Carotene Cancer Prevention Study,40 Lipid Research Clinics study,41 or Honolulu Heart Program.42 Modest, nonsignificant inverse associations were observed in the Multiple Risk Factor Intervention Trial,43 the Irish-Boston Heart Study,44and the Health Professionals Follow-Up Study.45 In the Health Professionals Follow-Up Study, CHD rates were lowest in participants with higher intake of both omega-3 and omega-6 PUFAs,46 and in the Western Electric Study47 and the Kupio Heart Study,48 higher LA intakes or serum levels were associated with lower risk of CHD or total mortality. In the Nurses’ Health Study, in which diet was assessed multiple times over 20 years,49 CHD risk was ≈25% lower comparing the 95th and 5th percentiles of LA intake (7.0% versus 2.8% of energy, respectively). Most prospective cohort studies have not found significant associations between omega-6 fatty acid intakes and ischemic50–52 or hemorrhagic50,51,53 stroke or stroke mortality.54 In 1 prospective study, serum LA levels predicted lower risk of stroke, particularly ischemic stroke.55 LA intakes are not associated with risk for cancer.26 Therefore, observational studies generally suggest an overall modest benefit of omega-6 PUFA intake on CHD risk and no significant effect on stroke or cancer. These studies, some of which included LA intakes of up to 10% to 12% of energy, contradict the supposition that higher omega-6 PUFA intakes increase risk for CHD.

Omega-6 PUFA Consumption and CHD Events: Randomized Controlled Trials

Several randomized trials have evaluated the effects of replacing saturated fatty acids with PUFAs on CHD events.56–65 Intakes of PUFA (almost entirely omega-6 PUFA) ranged from 11% to 21%. In addition to the inability to double-blind these studies, many had design limitations such as small sample size (n=54),65 the provision of only ≈50% of meals,56 outcomes composed largely of “soft” ECG end points,59,60 randomization of sites rather than individuals with open enrollment and high turnover of subjects,59,60 use of vegetable oils that also contained the plant omega-3 fatty acid α-linolenic acid,57,59,60 and simultaneous recommendations to increase fish and cod liver oil use.58Nevertheless, a meta-analysis including 6 of these trials56–60,62–64 indicated that replacing saturated fatty acids with PUFAs lowered the risk for CHD events by 24%.66 Of the remaining 4 studies, 1 reported a significant 45% reduction in risk,59 whereas no significant effect was seen in the others.60,61,65

These trials tested the effect of replacing saturated fatty acids; no randomized trial has reported the effects of replacing carbohydrate or protein with omega-6 PUFAs on CHD risk. Although limitations are present for each trial, the combined results of these studies and the observational trials provide evidence that replacing saturated fatty acid or refined carbohydrate (eg, sugars, white bread, white rice, potatoes) with omega-6 PUFAs reduces CHD risk. On the basis of the intakes of omega-6 PUFAs used in the randomized trials, metabolic studies, and nonhuman primate studies discussed below, reductions in CHD risk might be expected with omega-6 PUFA intakes of 10% to 21% of energy compared with lower intakes, with no clinical evidence for adverse events.

Recommended Intakes of Omega-6 Fatty Acids

Dietary recommendations for omega-6 PUFAs traditionally focused on the prevention of essential fatty acid deficiency but are now increasingly seeking to define “optimal” intakes to reduce risk for chronic disease, particularly CHD. The Institute of Medicine’s Food and Nutrition Board, in their Dietary Reference Intake Report for Energy and Macronutrients,67 defines an adequate intake of LA as 17 g/d for men and 12 g/d for women (5% to 6% of energy) 19 to 50 years of age, approximately the current median US intake. Both the Dietary Reference Intake Report and the 2005 Dietary Guidelines for Americans68 support an acceptable macronutrient distribution range (the range of intakes for a particular energy source that is associated with reduced risk of chronic disease while providing adequate intakes of essential nutrients) of 5% to 10% dietary energy from omega-6 PUFAs. The Third Adult Treatment Panel of the National Cholesterol Education Program recommends PUFA consumption up to 10%, noting that “there are no large populations that have consumed large quantities of polyunsaturated fatty acids for long periods. Thus, high intakes have not been proven safe in large populations; this introduces a note of caution for recommending high intakes.”69 On the other hand, evidence from trials in nonhuman primates has demonstrated cardiovascular benefits and no evidence of harm with LA intakes of 25% of energy for up to 5 years,70,71 and randomized trials in humans have shown reduced CHD risk with omega-6 PUFA intakes of 11% to 21% of energy for up to 11 years with no evidence of harm.

Other governmental health recommendations for omega-6 fatty acid intakes (on a percent energy basis) are as follows: European Commission, 4% to 8%72; Food and Agriculture Organization/World Health Organization, 5% to 8%73; British Nutrition Foundation, 6% to 6.5% (maximum, 10%)74; the Department of Health and Ageing, Australia and New Zealand, 4% to 5% (maximum, 10%)75; and the American Dietetic Association/Dietitians of Canada, 3% to 10%.76 The American Heart Association places primary emphasis on healthy eating patterns rather than on specific nutrient targets.

Advice to reduce omega-6 PUFA intakes is typically framed as a call to lower the ratio of dietary omega-6 to omega-3 PUFAs.1–4Although increasing omega-3 PUFA tissue levels does reduce the risk for CHD,77,78 it does not follow that decreasing omega-6 levels will do the same. Indeed, the evidence considered here suggests that it would have the opposite effect. Higher omega-6 PUFA intakes can inhibit the conversion of α-linolenic acid to eicosapentaenoic acid,79 but such conversion is already quite low,80 and whether additional small changes would have net effects on CHD risk after the other benefits of LA consumption are taken into account is not clear. The focus on ratios, rather than on levels of intake of each type of PUFA, has many conceptual and biological limitations.81

Conclusions

This advisory was undertaken to summarize the current evidence on the consumption of omega-6 PUFAs, particularly LA, and CHD risk. Aggregate data from randomized trials, case-control and cohort studies, and long-term animal feeding experiments indicate that the consumption of at least 5% to 10% of energy from omega-6 PUFAs reduces the risk of CHD relative to lower intakes. The data also suggest that higher intakes appear to be safe and may be even more beneficial (as part of a low–saturated-fat, low-cholesterol diet). In summary, the AHA supports an omega-6 PUFA intake of at least 5% to 10% of energy in the context of other AHA lifestyle and dietary recommendations. To reduce omega-6 PUFA intakes from their current levels would be more likely to increase than to decrease risk for CHD.

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  1. http://umm.edu/health/medical/altmed/supplement/omega6-fatty-acids