Omega-6 Fat Research News & Commentary

Omega-6 Fats Increase Risk of Blindness (AMD)

2009-12-12T01:41:37Z

Bottomline: Eating a diet high in omega-6 fats, from salad dressing, mayonnaise, and margarine, was associated with increased prevalence of age-related macular degeneration, a leading cause of blindness worldwide. Arch Ophthalmol.2009 Nov;127(11):1483-9

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the USA, and is expected to increase in prevalence by 50% in ten years.

Previous studies suggest a direct association between vegetable oils and AMD. Omega-6 fats is thought to contribute to retinal damage, via the inflammation cascade, which in turn may promote AMD.

Study: The relationship of dietary fat and AMD was evaluated in nearly 1800 women as part of the Carotenoids in Age-Related Eye Disease Study.

In women of all ages, omega-6 fats was directly associated with AMD, which is consistent with data in five previous studies on Americans.

Notably, omega-3 fats were associated with higher risk in women who ate more than 6% of their calories from omega-6 fats.

Previous studies have shown a protective effect of omega-3 fats (or fish) to be stronger among people who ate lower omega-6 diets. Therefore, a protective influence of omega-3 fats may depend on the intake of omega-6 polyunsaturated fatty acids.

Interestingly, the scientists note in this paper that some studies have found atherosclerosis to be associated with AMD.

Quote: "In this particular sample, adverse associations were particularly attributed to diets high in omega-6 fats..."

Source:

Parekh N, Voland RP, Moeller SM, Blodi BA, Ritenbaugh C, Chappell RJ, Wallace RB, Mares JA; CAREDS Research Study Group. Association between dietary fat intake and age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS): an ancillary study of the Women's Health Initiative. Arch Ophthalmol.2009 Nov;127(11):1483-93.

Why Omega-6 Fats Matter to Your Health

2009-11-10T21:48:00Z

BottomLine: Why Do Omega-6 Fats Matter for Health and Disease Prevention? Find out from pioneer scientist, Bill Lands, PhD. Video presentation, slides, and handout resources provided. (Note, all of this information is provided free for the sake of public health).

Background: Learn how most chronic diseases could be prevented by lowering omega-6 fats in the diet and why supplementing with fish oil and omega-3 fats is not enough.

Scientist, Bill Lands, PhD, cuts to the chase, and provides compelling reasons Americans need to re-think what constitutes a healthy diet. His engaging presentation was delivered at the National Institute's of Health two-day conference on omega-3 fats on October 14, 2009. What follows is a 37-minute video of his talk, slides, handouts and resource materials. Special thanks to Dr. Lands for graciously provided the slides used in his talk.

Feel free to distribute this information to friends, colleagues or via your blogs and websites. (Permission is granted, but we'd appreciate a credit line.)

Video: Due to the overwhelming response to this video, I had to change my source of video streaming. It's still free, and you can also download the video or forward it to your friends and colleagues. Here's what you do:

Just click on the screen or the url below. You will be taken to iAmplify, where you can view or download the video for free.

http://www.iamplify.com/store/product_details/Evelyn-Tribole-MS-RD/Learn-Why-Omega-6-Fats-Matter-to-Your-Health/product_id/6949

Slides: Nutritional Armor Slides ppt

Handout: This 19-page Handout includes a glossary, pdf of slides, study abstracts and resources.

Links to Resources:

Day 1 NIH Omega-3 Conference
Day 2 NIH Omega-3 Conference
KIM2 [Free online software program, developed by Dr. Lands, which analyzes your diet for omega-3 and omega-6 and risk for disease.]

www.EvelynTribole.com

Dietary Arachidonic Acid Increases Risk of Parkinson's Disease

2009-10-25T21:35:18Z

Bottomline: A case-control study indicates that eating higher levels of arachidonic acid, the omega-6 polyunsaturated fatty acid, increases the risk of Parkinson's Disease. J Neurological Sciences (2009).

Background: Parkinson's disease is a progressive movement disorder of the nervous system, that worsens over time, for which there is no cure. Fatty acids play a critical role in brain function. Previous case control studies indicate an association between eating animal fat and Parkinson's disease. Arachidonic acid is the omega-6 polyunsaturated fatty acid, which is found in animal fats including, meats, poultry and eggs.

Autopsies show significantly high levels of an arachidonic acid-derived compound, called isofurans, in a key brain region of deceased Parkinson's patients. This region of the brain, called the substantia nigra, is located in the midbrain, and its degeneration is implicated in Parkinson's disease.

Study: Patients who were diagnosed with Parkinson's disease (249 cases), were matched with 368 controls. Diets were evaluated using a diet history questionnaire, and the data were analyzed based on quartile intakes. (Potential confounding factors were also evaluated including, vitamin E, alcohol and body mass index).

Arachidonic acid was significantly related to an increased risk of Parkinson's disease, with a signifiant positive linear trend. Men in the highest quartile of arachidonic acid intake had nearly three times the risk for Parkinson's disease, compared to the lowest quartile intake. While, women had a two-fold increase risk, compared to the lowest quartile consumption of arachidonic acid.

Interestingly, there was a positive relationship between cholesterol intake and Parkinson's disease.

Quote:"High arachidonic acid consumption could increase the risk of Parkinson's disease via an inflammatory process."

Comment: The average arachidonic acid consumed in the highest quartile was greater than 171 milligrams/day. To put that into perspective, 3-ounces of dark meat turkey, without the skin, contains 220 milligrams of arachidonic acid. To get more information on arachidonic acid in foods see: How Much Arachidonic Acid in Meats and Poultry? The Free Omega-6 Fat Tracker Widget

Link to Study:
Miyake Y, et al, Dietary fat intake and risk of Parkinson's disease: A case-control study in Japan. J Neurol Sci (2009),
doi:10.1016/j.jns.2009.09.021

Prostate Cancer Growth Increases with Omega-6 Diet, but Slows with Omega-3.

2009-09-28T02:12:00Z

Bottomline: A cleverly designed study shows that high dietary omega-6 fat triggers tumor growth, in an animal model of prostate cancer, while dietary omega-3 fat attenuates. Neoplasia (2009):11(7):692-699

Background: Prostate cancer is one of the leading causes of death among men in the USA. Previous studies implicate the imbalance of dietary omega-6 and omega-3 fats, in part, for the high occurrence of prostate cancer.

Recent data show that two key enzymes are increased in prostate tumor tissues, compared to normal tissues. One of these enzymes is 15-lipoxygenase-1 (15-LOX-1), which prefers linoleic acid, rather than arachidonic acid (both of which are omega-6 polyunsaturated fatty acids.) The compound created from the union of linoleic acid and 15-LOX-1, contributes to the initiation and development of prostate cancer.

The other enzyme that increases in prostate cancer is COX-2, which acts on arachidonic acid to create PGE-2, which is also implicated in prostate cancer (and other cancers as well, see China Study Shows Dietary Arachidonic Acid Ups Risk for Colorectal Cancer.)

A recent study, demonstrated that prostate cancer cell growth was inhibited, with the combination of DHA and celecoxib (a medication which is a specific COX-2 inhibitor).

Enter the EPA factor. When the above two enzymes (5-LOX-1 and COX-2), joins with EPA, it creates anti-inflammatory and anti-tumorogenic compounds. Taken together, there is a double beneficial effect with increased dietary EPA:

Increases anti-tumorogenic compounds
Decreases the availability of these enzymes to make tumor promoting compounds from omega-6 fat.

Therefore the researchers theorized that prostate tumor growth can be modulated by "dietarily targeting" the 5-LOX-1 and COX-2 enzymes.

Study: An animal model of prostate cancer was used. The mice were injected with prostate cancer-promoting cells and divided into three-isocaloric diets: the control diet, high linoleic acid (omega-6) diet and high omega-3 diet. (Note, because of cost constraints, the researchers used the omega-3 fatty acid, stearidonic acid, which is the precursor to EPA.)

This was a 28-week dietary study, with a crossover-design at week 23. At week 23, the high omega-6 diet group was switched over to the high omega-3 diet, and visa versa, the omega-3 fed mice were crossed-over to the omega-6 diet. At week 28 tumors were evaluated for growth, fatty acids, enzyme activities, apoptosis and proliferation.

Results: Tumors from the high omega-6 diet group had the most rapid growth. Yet, when this omega-6 fed group was switched to the omega-3 diet, there was a dramatic decrease in tumor growth. When the omega-3 diet group was switched to the omega-6 diet, the tumors grew more aggressively.

The omega-6 and omega-3 fatty acid composition of red blood cells and tumor cells, reflected the diet, and modulated accordingly. The tumors from the high omega-6 group, had a higher ratio of omega-6:omega-3 fat, nearly 7-fold, compared to the control group. Similarly, the tumors from the omega-3 fed group, had a 4-fold decrease in the ratio, compared to the control.

Conclusion: Dietary omega-6 and omega-3 fatty acids, effects cell composition, which in turn, influence the activities of enzymes, 15-LO-1 and COX, which effect prostate cancer growth. When EPA competes with arachidonic and linoleic acid, for COX and 15-LO-1 enzymes, respectively, it slows prostate cancer growth by creating tumor inhibiting compounds.

Quote: "Importantly, these results further corroborate that SDA (and EPA) does not inhibit either 15-LO-1 or COX, and tumor growth reflects the substrate competition of omega-3 and omega-6 fatty acids."

Link to Full Text Study:
Kelavkar U et al. Prostate tumor growth can be modulated by dietarily targeting the 15-lipoxygenase-1 and cyclooxygenase-2 enzymes.
Neoplasia (2009):11(7):692-699.

www.EvelynTribole.com

High Omega-6 Associated with Infertility and Low Sperm Count

2009-08-26T03:11:00Z

Bottom-line: First ever study shows that sperm count and sperm motility is effected by the balance of omega-6 and omega-3 fats. Clinical Nutrition 2009 Aug 8..

Background: There is a growing body of evidence that the fatty acid composition of sperm, determines physiological characteristics, which in turn may affect fertility. It is estimated than 25% of infertility cases are due to poor semen quality. In humans, sperm motility strongly correlates with sperm membrane DHA levels.

Study: Researchers evaluated the fatty acid composition in sperm on fertility parameters in eighty-two infertile men and seventy-eight age matched fertile men, which served as controls. The fatty acids analyzed were ALA, EPA and DHA, and two omega-6 polyunsaturated fatty acids – linoleic acid and arachidonic acid. The ratios of omega-6/omega-3 and the omega-3 index were also calculated.

Findings: A high proportion of omega-6 polyunsaturated fatty acids was found to be a distinctive feature of infertile men.

Notably, a higher omega-6 fat composition of sperm was associated with lower: sperm motility, sperm count and normal sperm morphology. Specifically, the sperm of infertile men had higher levels of:

Arachidonic acid
Ratio of Arachidonic acid to DHA
Ratio of Arachidonic acid to EPA

Conversely, omega-3 fatty acid composition had a favorable association with semen parameters (motility, sperm count and morphology). Also, the omega-3 index was lower in infertile mean compared to the controls.

The researchers believe that impaired fertility of men could be due, in part, to the reduced sperm membrane fluidity, which is greatly effected by the composition of fatty acids.

Quote: “The possibility that diets poor in omega-3 polyunsaturated fatty acids and rich in omega-6 polyunsaturated fatty acids contribute to poor semen quality and sperm function is becoming increasingly recognized.”

Comment:

The fluidity of cell membranes is greatly effected by the types of fatty acids tethered in its phospholipids. The more double-bonds in a fatty acid, the more flexible the structure becomes. Each double-bond is like a flexible gate hinge. The omega-6 fatty acid, arachidonic acid has 4 double-bonds, but the omega-3 fatty acids, EPA and DHA have more, which confers more fluidity:

EPA has 5 double-bonds
DHA has 6 double-bond

Link to Study:

Safarinejad MR et al. Relationship of omega-3 and omega-6 fatty acids with semen characteristics, and anti-oxidant status of seminal plasma: A comparison between fertile and infertile men. Clinical Nutrition 2009 Aug 8.

Further Reading:

AA Zalata , AB Christophe , CE Depuydt , F Schoonjans , and FH Comhaire. The fatty acid composition of phospholipids of spermatozoa from in fertile patients Mol. Hum. Reprod. (1998) 4: 111-118 [free full text ].

China Study Shows Dietary Arachidonic Acid Ups Risk for Colorectal Cancer

2009-08-13T18:02:00Z

Bottomline: Dietary arachidonic acid (the omega-6 polyunsaturated fat found in animal foods), and a high dietary ratio of omega-6 to omega-3 polyunsaturated fatty acid increased the risk of developing colorectal cancer according to findings from a large study. Cancer Epidemiol. Biomarkers Prev. 2009 18: 2283-2291.

Background: Colorectal cancer is the leading cause of cancer-related deaths. Omega-3 and omega-6 polyunsaturated fatty acids use many of the same biochemical pathways, but produce eicosanoids with profoundly different effects. (Eicosanoids include prostaglandins, leukotrienes and thromboxanes.) Ultimately, the type of eicosanoids produced may be determined by dietary intakes of omega-3 and omega-6 polyunsaturated fatty acids.

Of particular interest is the prostaglandin E2 (PGE2), a pro-inflammatory compound, which is associated with a high risk of colorectal cancer. Notably, PGE2 is derived from arachidonic acid, which is facilitated by the cyclooxygenase (COX) enzymes. But the omega-3 polyunsaturated fatty acid, EPA, also uses COX enzymes, which form other prostaglandins.

Study: Scientists wanted to explore if diets lower in arachidonic acid (and other omega-6 fats), in conjunction with higher EPA and other omega-3 fats, are associated with a lower production of PGE2, and ultimately, a lower risk of colorectal cancer.

Data from a large prospective cohort study on nearly 75,000 Chinese women (from the Shanghai Women’s Health Study) were evaluated for a urinary metabolite of PGE2, dietary fatty acids, diet, lifestyle and medication use. They found a strong association of colorectal cancer risk with the:

• Ratio of dietary omega-6 to omega-3 polyunsaturated fatty acids
• Absolute intake of dietary arachidonic acid

Additionally, the total dietary omega-6 to omega-3 was positively associated with the urinary PGE2 biomarker.

The research team also found a possible reason for conflicting results from other studies, which showed no relationship between dietary omega-3 and omega-6 and colorectal cancer risk.

Previous studies show that taking fish oil supplements suppress PGE2, only if people eat a diet with a low ratio of omega-6 to omega-3 fats of 2.5:1. The fish oil benefit was not achieved with higher dietary ratios. Therefore, it’s possible that benefits of eating a low ratio of omega-6 to omega-3 fats is only detectable below an absolute threshold.

Notablely, the Chinese women in this study ate a median daily linoleic acid intake of 5.9 grams, with a ratio of omega-6 to omega-3 fats of about 6:1. Whereas, American women eat nearly double that amount of omega-6 fat (11 grams per day), with a ratio of omega-6 to omega-3 fats of about 16:1. Therefore, the lack of apparent association in previous studies may be due to consumption omega-6 fats too high above the potential toxic threshold level to see an effect.

Quote: “These findings are intriguing and suggest that dietary fatty acid intake could alter the production of inflammatory prostanoids and consequently the risk of colorectal cancer but that this protective effect may only be at earlier stages of colon carcinogenesis.”

Comment: These findings are especially notable, given that a study published this week in the Journal of the American Medical Association (August 12) showed that taking aspirin improves survival of patients diagnosed with colorectal cancer. Aspirin inhibits COX-2 enzymes, which are over-expressed in 80-85% of colorectal cancers. Recall that COX enzymes convert arachidonic acid into (PGE2), the pro-inflammatory compound, which is associated with a high risk of colorectal cancer.

Imagine the possibilities of an intervention study on colorectal cancer patients, evaluating the efficacy of a low-omega-6 fat diet (with adequate omega-3 fatty acids). Unlike aspirin, there are no side-effects from eating a lower omega-6 diet (which in essence, is the classic Mediterranean diet, the components of which, were replicated in the Lyon Diet Heart trial).

For information on dietary sources of omega-6 fats, see:

Links to Studies:

Murff HJ, Shu XO, Li H, Dai Q, Kallianpur A, Yang G, Cai H, Wen W, Gao YT, and Zheng W.
A Prospective Study of Dietary Polyunsaturated Fatty Acids and Colorectal Cancer Risk in Chinese Women.
Cancer Epidemiol. Biomarkers Prev. 2009 18: 2283-2291.

Andrew T. Chan; Shuji Ogino; Charles S. Fuchs
Aspirin Use and Survival After Diagnosis of Colorectal Cancer.
JAMA. 2009;302(6):649-658.

Omega-6 Fat Associated with Insulin Resistance and Metabolic Syndrome

2009-08-05T07:00:00Z

Bottomline: Results from the first-ever study on people with metabolic syndrome, showed that insulin resistance is independently associated with higher omega-6 fat levels. Conversely, omega-3 levels are protective. Nutrition, Metabolism and Cardiovascular Diseases, 2009.19(4): 264-270.

Background: Metabolic syndrome is a constellation of symptoms including three out of the five following characteristics: elevated triglycerides, low HDL-cholesterol, elevated glucose, abdominal obesity, and high blood pressure. Metabolic syndrome increases the risk of cardiovascular disease.

Previous studies have shown that people with elevated levels of omega-6 fatty acids and saturated fatty acids are at higher risk of developing diabetes and heart disease. Animal studies indicate that omega-3 fatty acids, EPA and DHA, may prevent the development of insulin resistance. But studies on people have yielded conflicting results.

Study: This is the first study to evaluate the relationship between plasma omega-3 and omega-6 polyunsaturated fatty acids to insulin resistance, independently of other known factors in patients with metabolic syndrome and underlying heart disease.

A total of 734 people enrolled in a secondary CHD prospective cohort study were evaluated for metabolic syndrome, fatty acid plasma profiles, insulin resistance and clinical parameters.

The key findings:

People with metabolic syndrome have higher plasma levels of saturated fats and omega-6 plasma fatty acids.

The relationships between omega-3 and omega-6 polyunsaturated fatty acids levels in patients with metabolic syndrome were independent of other factors associated with metabolic syndrome andinsulin resistance (waist circumference, HDL-cholesterol, gender, age,triglycerides, saturated fats and blood pressure.)

A higher ratio of plasma omega-6 to omega-3 fatty acids was associated with insulin resistance only in patients with metabolic syndrome.

Omega-3 and omega-6 polyunsaturated fatty acids had opposing effects on insulin resistance. EPA was associated with better glucose balance, while omega-6 polyunsaturated fatty acids were associated with elevated insulin resistance.

Quote: “…our data suggest that omega-3 and omega-6 polyunsaturated fatty acids may have opposing effects on insulin resistance.”

Link to Study:
A. Nigam, N. Frasure-Smith, F. Lespérance, P. Julien
Relationship between n-3 and n-6 plasma fatty acid levels and insulin resistance in coronary patients with and without metabolic syndrome. Nutrition, Metabolism and Cardiovascular Diseases, 2009.19(4): 264-270.[abstract].

“Heart Healthy” Omega-6 Polyunsaturated Fat Doubles Risk for Ulcerative Colitis

2009-07-24T17:23:00Z

Bottomline: Dietary linoleic acid, the most commonly eaten omega-6 polyunsaturated fatty acid, doubles the risk of developing ulcerative colitis, according to large European study. Gut 2009 0: gut.2008.169078

Background: Ulcerative colitis is a chronic inflammatory disease, which hampers quality of life and increases the risk of colon cancer. The cause of this disease is not known, but researchers believe it may be related to excess omega-6 polyunsaturated fat in the diet, because:

•   Omega-6 derived, pro-inflammatory eicosanoids are present in high levels in the intestinal lining of patients and in animal models of this disease.

•    The level of these to pro-inflammatory eicosanoids correlate with the amount of tissue damage.

•    The first-line medications used to manage ulcerative colitis contain 5-aminosalicyclic compounds, suppress pro-inflammatory eicosanoids levels, in a dose-dependent manner.

Dietary linoleic acid is the chief omega-6 polyunsaturated fat eaten in westernized countries, which has increased markedly in the last century. Linoleic acid is found in soybean oil, corn oil, cottonseed oil, margarines, and salad dressings.

Study:This is the first prospective cohort study evaluating dietary linoleic acid intake and the risk of developing ulcerative colitis.

Over 200,000 men and women (yes, nearly a quarter-of-a-million people), ages 30-74. were enrolled in this study. Note these people were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which spans 10 countries. All participants were free of ulcerative colitis when enrolled in the study.

Diet was evaluated by country-specific food frequency questionnaires, which were validated against 24 hr recall questionnaires and plasma and urinary biomarkers for specific nutrients. In the analysis, using a nested case–control method, each person that developed ulcerative colitis was matched with four randomly selected controls.

Results: A high dietary intake of the omega-6 polyunsaturated fatty acid, linoleic acid, more than doubled the risk of developing ulcerative colitis. Even when the scientists adjusted for aspirin usage, the effect of linoleic acid remained statistically significant.

Nearly one-third of the cases of ulcerative colitis were attributed to the dietary linoleic acid levels among the highest three quartiles, as shown below:

Of note, the omega-3 fatty acid, DHA, was associated with a reduced risk of developing ulcerative colitis.

Quote:“…there is substantial potential for reducing the incidence of ulcerative colitis through dietary modification.”

Comment: Note that eating daily amounts of linoleic acid higher than 6.1 grams for women and 7.8 grams for men, were associated with increased risk of developing ulcerative colitis. To put that into perspective, the mean intake of linoleic acid in the USA is 13.0 grams per day (USDA-ARS, 2001).

The top sources of linoleic acid in the USA are soybean oil, cottonseed oil, corn oil and many of so-called “heart healthy” foods made with these oils, including many margarines. To get an idea of the linoleic acid content of vegetable oils see: How Much Omega-6 in Vegetable Oils? The Omega-6 Fat Tracker Widget

The classic Mediterranean diet, replicated in the Lyon Diet Heart study, is low in omega-6 fatty acids, similar to the levels found in the no-risk quartiles in this EPIC study. For more information see:

The Mediterranean Diet is Low in Omega-6 Fat, Say Lyon Diet Heart Study Scientists and

What Everyone Ought to Know About the Mediterranean Diet

Link to Study:.
Hart, ARLinoleic Acid, a Dietary N-6 Polyunsaturated Fatty Acid, and the Aetiology of Ulcerative Colitis - A European Prospective Cohort Study.Gut 2009 0: gut.2008.169078s, see:

Dietary Fats Omega-6 and Omega-3: Impact Your Inflammation Gene Machine

2009-07-20T16:43:00Z

Bottomline: The first human study shows that modifying diet changes the cellular levels of omega-6 and omega-3 polyunsaturated fatty acids, which directly impact inflammation genes. J Biol Chem. 2009 Jun 5;284(23):15400-7.

Background: Inflammatory diseases are on the rise. It is estimated that within the next two decades, more than one in three Americans will have an inflammatory disease, which include heart disease, asthma and rheumatoid arthritis. Many scientists believe this upward trend is due to the dramatic rise in dietary omega-6 polyunsaturated fats, which outnumber omega-3 fats, by 10 to 1, in the typical American diet. In contrast, our hunter-gatherer ancestors consumed an estimated one-to-one balance of these fats.

Studies indicated that eating excess dietary omega-6 fat, increases the omega-6 derived eicosanoids, (which include leukotrienes); which in turn, may lead to a systemic pro-inflammatory state in the body. For example, when the LOX enzyme acts on the omega-6 fatty acid, arachidonic acid, it creates the potent leukotriene, LTB4, (which is the compound implicated in asthma and atherosclerosis). Yet, if this enzyme acts on the omega-3 fatty acid, EPA, it creates leukotriene compounds that are 10 to 100-fold less potent.

Additionally, animal studies indicate that polyunsaturated fatty acids modulate the genes effecting inflammation. But whether that holds true for people, has been unknown, until this study.

Study: Healthy volunteers (27), were fed a controlled background diet for five weeks. After the first week, they were given supplemental fish oil and borage oil for a four-week period, which provided 775 mg EPA and 831 mg GLA. Then on the sixth and seventh weeks, the volunteers resumed their normal diet, comprising a two-week washout-out period. Weekly blood samples were evaluated for: fatty acid distribution in serum and neutrophils, leukotriene metabolites, cytokines, and the genes influencing eicosanoid and cytokine formation.

Results: In the neutrophil cells, there was a marked 40% reduction in the omega-6 to omega-3 fatty acid ratio, which resulted in a 55% decrease of LTB4 production in the “responders” group, as shown below:

There was a significant decrease in pro-inflammatory cytokines. The researchers noted their surprise on finding a marked decrease in the expression of a key regulatory compound, P13K, which influences eicosanoid and cytokine formation, cell growth, cell survival and inflammation.

Conclusion: Altering the omega-6 and omega-3 polyunsaturated fatty acids in healthy volunteers, resulted in a markedly changed fatty acid composition in neutrophils, which inhibited their capacity to generate leukotriene LTB4, a potent biomarker of inflammation. Most notably, polyunsaturated fatty acids impacted the expression of proinflammatory cytokine genes and signal transduction genes, with a decrease in several proinflammatory cytokines.

Quote: “This report demonstrates, for the first time in humans, that the expression of an early step (P13K) in signal transduction, as well as several important downstream effectors are significantly reduced by altering ingestion of polyunsaturated fatty acids to shift circulating omega-6 to omega-3 ratios.”

Comments: Attention to the background diet is often a missing design element in supplementation studies, which is necessary to observe consistent changes in cellular fatty acid distribution.

This study not only controlled the background diet, it included an evaluation of the transient effect of diet on cellular levels of fatty acid composition; which was elegantly demonstrated, by adding a two-week period of normal eating (weeks 6 and 7). Notably, the ratio of cellular arachidonic acid to EPA decreased by 75%, during the “study period”, but increased to near the baseline levels, after the volunteers returned to their normal eating patterns. This was also true for LTB4 levels.

Study:
Weaver KL, Ivester P, Seeds M, Case LD, Arm JP, and Chilton FH.
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans J Biol Chem. 2009 Jun 5;284(23):15400-7[abstract]

Dietary Omega-6 Increases Risk of Depression

2009-07-11T17:15:00Z

Bottomline: A large 10-year follow-up study shows that omega-6 fatty acids in the American diet significantly increase the risk of depression in men. Prog Neuro-Psychopharmacol Biol Psychiatry (2009).

Background: A recent study spanning 60 countries and 250,000 people indicated that depression produces the greatest decrement in health compared with the chronic diseases of angina, arthritis, asthma, and diabetes. Depression strikes 17 million Americans per year, more than cancer and heart disease, combined.

In the past century, there has been a dramatic rise in the consumption of polyunsaturated omega-6 fatty acids, predominantly from vegetable oils, at the expense of omega-3 fatty acids. Linoleic acid is the most commonly eaten omega-6 polyunsaturated fat in westernized countries.

Earlier studies indicate that depressed patients have: higher omega-6 fatty acids in their tissues and elevated proinflammatory omega-6 compounds such as thromboxanes, leukotrienes and cytokines.

Study:The association between severe depressed mood and dietary fatty acids were assessed among nearly 5000 adults aged 25–74 years who were examined in 1971–1975 as a part of a the National Health and Nutrition Examination Survey Epidemiology (NHES). The subjects in this study had an average of 10.6 years of follow-up.

Depression was assessed using the Center for Epidemiologic Studies Depression Scale questionnaire. Dietary fatty acid intake was evaluated using a 24-hour recall method, administered by dietitians, who also used food models to help the subjects assess their portions of food eaten.

Findings: There was a dose–response association between linoleic acid (omega-6) intake and depression among men. Men in the highest tertile group of linoleic intake (averaging 19 grams of dietary linoleic acid/day) had twice the risk being depressed compared to those in lowest third intake group, who ate on average 3.5 grams of linoleic acid/day. Notably, these risk estimates were adjusted for fish consumption.

Oleic fatty acid (the chief fatty acid in olive oil) was associated with a decreased risk of depression among women in a dose–response relationship. The authors concluded that a higher intake of oleic fatty acid reduced the risk of depression among women while increased intake of linoleic acid increased the risk of severe depressed mood among men.

Study quote: "The current study provides strong evidence that diets rich in omega-6 fatty acids may enhance the risk of depression among general population".

Comment: Experimental studies show that eicosapentaenoic acid (EPA), the omega-3 fat associated with mood improvement, is reduced in the cells, as a consequence of eating a diet high in omega-6 fat. (See High Omega-6 Diet Lowers Omega-3 Status, but Low Omega-6 Diet Preserves)

To get an idea of the linoleic acid content in food check out the Omega-6 Fat Tracker widget: How Much Omega-6 in Vegetable Oils? The Omega-6 Fat Tracker Widget

While the results from this study were different for men and women, the findings still fit with the benefits of eating a classic Mediterranean diet,which is low in omega-6 fat and rich in omega-9 fat (olive oil)--for more details see:

Link to Study:

Wolfe AR, Ogbonna EM, Lim S, Li Y, Zhang J.
Dietary linoleic and oleic fatty acids in relation to severe depressed mood: 10 years follow-up of a national cohort.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 May 6. doi:10.1016/j.pnpbp.2009.05.002

Mom’s High Omega-6 Diet Increases Eczema Risk in Their Infants

2009-06-21T19:29:00Z

Bottomline: Pregnant women who ate the highest amount of omega-6 polyunsaturated fats, resulted in a higher risk of childhood eczema for their infants. Thorax. Online First: 3 June 2009

Background: Polyunsaturated fatty acids and their derivatives can influence the antenatal immune responses, including the balance of the cytokines TH1 and TH2. A German cohort study showed significant positive associations of maternal intake of margarine and vegetable oils during pregnancy with the risk of eczema during the first two years in children. (The great majority of margarines and vegetables are high in omega-6 polyunsaturated fats).

Study: Data from the 16- to 24-month follow-up of the Osaka Maternal and Child Health Study (OMCHS), involving 763 mother-child pairs was analyzed for the relation between maternal intake of fatty acids, cholesterol, meat, and fish during pregnancy and the risk of wheeze and eczema in infants in Japan.

The diagnosis for wheeze and eczema met the criteria of International Study of Asthma and Allergies in Childhood (ISAAC). Of the 763 infants 169 (22.1%) and 142 (18.6%) had symptoms of wheeze and eczema based on the ISAAC criteria, respectively.

Maternal intake of n-6 polyunsaturated fatty acids and linoleic acid during pregnancy in the highest quartile was independently associated with an increased risk of infantile eczema, showing clear inverse exposure-response relationships.

Study Quote: “Our results suggest that maternal intake of α-linolenic acid and docosahexaenoic acid during pregnancy may be preventive against infantile wheeze whereas maternal intake of n-6 polyunsaturated fatty acids, especially linoleic acid, during pregnancy may increase the risk of childhood eczema.”

Link to Study:
Miyake Y et al.
Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese infants aged 16-24 months: The Osaka Maternal and Child Health Study. Thorax. Published Online First: 3 June 2009. doi:10.1136/thx.2009.115931

High Omega-6 Diet Lowers Omega-3 Status, but Low Omega-6 Diet Preserves

2009-05-23T04:01:00Z

Bottomline: Healthy men fed a high omega-6 fat diet resulted in lower EPA blood levels, compared to those given a low omega-6 fat diet. Researchers conclude that the typical western diet, high in omega-6 fat is pro-inflammatory.
Prostaglandins, Leukotrienes and Essential Fatty Acids - April 2009: 201-206.

Background: Linoleic acid, an omega-6 fatty acid, accounts for 90% of the polyunsaturated fat consumption in western countries. There has been a dramatic increase in the food supply of omega-6 fats since the 1900s.

Linoleic acid competes with omega-3 fatty acid, alpha linolenic acid, for key enzymes, which are in limited supply. This competitive factor, combined with high intakes of dietary linoleic acid, can reduce the cellular levels of the potent omega-3 fatty acids, EPA and DHA. Consequently, this alters the balance of omega-3- and omega-6-fatty acids in the cells, which ultimately effects eicosanoid formation (leukotrienes, thromboxanes, prostaglandins, and lipoxins).

Study:This randomized cross-over study, involved 21 adult men, 20–45yr of age. They were fed either a low omega-6 fat diet (4% of total calories from linoleic acid), or a high omega-6 fat diet (10% of total calories). Both diets had 1% of calories from alpha linolenic acid, which respectively provides dietary omega-6/omega-3 ratios of 10:1 to 4:1.

An increase in linoleic acid intakes from 4% energy to 10% energy resulted in an increase in 20:2n-6 and decrease in EPA, suggesting increased metabolism of linoleic acid by direct elongation and inhibition of alpha linolenic acid conversion to EPA. Conversely, decreasing dietary linoleic acid resulted in a two-fold increase of EPA in the cells.

There was no increase in arachidonic acid, which is consistent with other findings, indicating that 3% energy linoleic acid is too high and floods the fatty acid metabolic pathway. The researchers believe that alpha linolenic acid functions to constrain linoleic acid conversion to arachidonic acid, and is most likely to be evident at linoleic acid/alpha linolenic acid ratios below 4:1.

Conclusion: Since the phospholipid arachidonic acid/EPA ratios were higher in men consuming 10% omega-6 fat diet compared to the 4% omega-6 fat, it is consistent with the concern that current western diets promote a pro-inflammatory environment.

Study Quote: “Our studies add to the concern that current intakes and recommendations for linoleic acid are high, while intakes of alpha-linoleic acid are so low as to contribute to a high tissue arachidonic acid/omega-3 fatty acids balance through suppression of omega-3 fatty acids metabolism."

Link to Study:
Y. Angela Liou and Sheila M. Innis
Dietary linoleic acid has no effect on arachidonic acid, but increases n-6 eicosadienoic acid, and lowers dihomo-γ-linolenic and eicosapentaenoic acid in plasma of adult men. Prostaglandins, Leukotrienes and Essential Fatty Acids - April 2009: 201-206.

Mental Retardation is Associated with Abnormal Omega-6 and Omega-3 fatty acid Levels

2009-04-09T20:09:00Z

Bottomline: Plasma levels of omega-6 fatty acids were significantly higher, while omega-3 fatty acid levels were significantly lower in children with mental retardation, according to the results of the first ever matched case control study. Asia Pac J Clin Nutr. 2009;18(1):22-8.

Background: A large body of research implicates fatty acid imbalances with various neurological disorders including, dyslexia, attention-deficit hyperactivity disorder (ADHD), mood disorders and learning disorders. Particularly, elevated levels of omega-6 fatty acids are associated with dysfunction, while omega-3 fatty acid levels, particularly EPA and DHA are associated with neuroprotection. Mental retardation effects about 1% of school-age children. While genetics is a significant factor, up to 60% of cases are from unknown causes.

Summary: In this age-matched case control study, researchers identified 31 school-age children from Korea, who met the American Psychiatric Association's Diagnostic and Statistical Manuals (DSM) criteria for mental retardation. Healthy children were recruited as controls from the same areas as the special education school from which the cases were selected. Plasma phospholipid fatty acids, plasma lipoproteins and other lipids were measured and evaluated.

Total omega-3 fatty acids levels were significantly lower in cases as compared to controls. In particular, for each unit increase in plasma DHA, the odds of mental retardation decreased by 74%. On the other hand, the odds of mental retardation increased significantly with an increase in the total omega-6 fatty acid plasma levels.

No difference in diet were found between the groups of children. However, only one-day of the children's diet was recorded and evaluated, the duration of which the researchers acknowledged as a significant limitation.

Study Quote: "the odds of mental retardation were estimated to increase by 69% for each unit increase in the omega-6 to omega-3 (ratio in the plasma)."

Link to Study:
Neggers YH, Kim EK, Song JM, Chung EJ, Um YS, Park T.
Mental retardation is associated with plasma omega-3 fatty acid levels and the omega-3/omega-6 ratio in children.
Asia Pac J Clin Nutr. 2009;18(1):22-8.

Dietary Arachidonic Acid Increases Risk of Thrombus (Blood Clot)

2009-04-01T19:58:00Z

Bottomline: Eating a high arachidonic acid diet resulted in an increase of the potent compound, thromboxane, which may increase the risk of arterial blood clots.

Background: Since omega-6 polyunsaturated fatty acids have been in the headlines, this research brief reviews a classic study, which has striking implications on heart health.

In 1997, a series of metabolic studies evaluated the impact of eating a high arachidonic acid diet on healthy men. Arachidonic acid is the omega-6 fatty acid found in animal foods and is the potent precursor to thromboxane and prostacyclin. These compounds are key players in blood vessel physiology effecting the formation of intra-arterial blood clots. Thromboxane is a powerful inducer of platelet aggregation and vasoconstriction, while prostacyclin is its biological opposite.

Summary:This was a single blind crossover, feeding study in which 10 healthy volunteers lived in a metabolic unit for 130 days--with an intervention period of 50-days eating a high arachidonic acid diet (1.5 grams/day) and a control period of 65-days for each subject.

When the men ate a high arachidonic acid diet (1.5 grams/day), they experienced a marked increase in arachidonic acid-derived vasoactive compounds, compared to when they ate a stabilizing diet with 210 mg/d of arachidonic acid. Thromboxane levels increased by 41% and prostacyclin increased by 27%, compared to baseline levels. Since there was a considerable increase in thromboxane levels compared to prostacyclin, the researchers concluded that increasing dietary arachidonic acid could increase the risk of thrombosis.

Study Quote:”The magnitude of these increases is, in our opinion, remarkable as they occurred through the action of only 0.5 en% of added arachidonic acid and in the presence of relatively large quantities of dietary linoleate, the precursor of arachidonic acid.

Comment: Most cases of myocardial infarction are due to the formation of an occluding thrombus (blood clot) on the surface of the arterial plaque [Hansson]. For information on the the arachidonic acid content of foods, see: How Much Arachidonic Acid in Meats and Poultry? The Free Omega-6 Fat Tracker Widget

Links to Sources:
Ferretti A, Nelson GJ, Schmidt PC, Kelley DS, Bartolini G, Flanagan VP. Increased dietary arachidonic acid enhances the synthesis of vasoactive eicosanoids in humans. Lipids. 1997 Apr;32(4):435-9.

Hansson, G. Mechanisms of disease Inflammation, Atherosclerosis, and Coronary Artery Disease. New England Journal of Medicine. 2005;352:1685-95.

Omega-3 Supplements Work Better with a Low Omega-6 Fat Diet

2009-03-06T22:48:00Z

Bottomline: Eating a low omega-6 fat diet helped boost the plasma levels of omega-3 fats in children who were supplemented with fish oil.

Asia Pac J Clin Nutr. 2008;17(4):552-7.

Background: There are conflicting results on the effectiveness of fish oil for treating and preventing asthma. Omega-6 fats compete with omega-3 fats in many biochemical pathways, which influences inflammation. Yet despite this interaction, the background levels of dietary omega-6 fat are rarely controlled in studies evaluating the efficacy of fish oil and omega-3 fatty acids,which may explain the inconsistent results.

Summary: Data from the Childhood Asthma Prevention Study (CAPS) clinical trial, was used to investigate the impact of omega-6 fatty acids in the background diet, on the effect of the omega-3 supplementation.

The study was a randomized, parallel-group controlled trial. Pregnant women whose unborn children were at increased risk of developing asthma, were recruited and then randomized antenatally into either the control or intervention group.

The intervention diet group received tuna oil supplements in conjunction with a low omega-6 fat diet. Supplementation began when the child started bottle feeding or at age six months, which ever was earlier.

Dietary intake was assessed at 18 months by 3–day weighed food record and at 3 years by food frequency questionnaire. Plasma phospholipids were also measured at these time points.

Results: Omega-6 fatty acids in the diet were inversely related to lower plasma levels of omega-3 fatty acids. A one gram increase in the dietary intake of omega-6 fatty acids was associated with a 0.16% decrease in plasma n–3 PUFA levels at 18 months and a 0.05% decrease in plasma omega-3 fatty acids at three years.

Dietary intake of omega-6 fatty acids was positively associated with plasma omega-6 fatty acids levels in both groups. These findings also supports earlier work showing that omega-6 fatty acids biochemically compete with omega-3 fatty acids.

Study Quote:..."the effectiveness of omega-3 fatty polyunsaturated acid supplementation in increasing plasma omega-3 fatty polyunsaturated acid levels is enhanced by restricting background dietary intake of omega-6 polyunsaturated fatty acids."

Source:

Hoyos C, Almqvist C, Garden F, Xuan W, Oddy WH, Marks GB, and Webb KL.
Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on plasma fatty acid levels in the first 3 years of life.
Asia Pac J Clin Nutr. 2008;17(4):552-7.

Omega-3s Protects Against Nonalcoholic Fatty Liver Disease & Blocks Omega-6 Fat Compounds

2009-02-24T20:47:00Z

Bottomline: Omega-3 fatty acids protected the liver from damage, triggered by obesity and insulin resistance. Omega-3s blocked inflammatory compounds derived from the omega-6 fatty acid, arachidonic acid; while creating liver-protecting compounds, called resolvins and protectins.
FASEBJ February 11, 2009.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, which can ultimately lead to liver failure. This condition is triggered by metabolic syndrome (obesity and insulin resistance), which results in the accumulation of fat in the liver, which creates inflammation and scarring (cirrhosis).

While the omega-3 fatty acids, DHA and EPA, are well known for their anti-inflammatory properties, scientists recently discovered that they generate potent bioactive mediators, called Resolvins and protectins, which have profound protective properties. Since obesity is characterized as a low grade inflammatory state, and fat cells secrete compounds which modulate both inflammation and insulin; researchers wanted to explore the impact of omega-3 fats on this condition.

Summary: Scientists evaluated whether omega-3-polyunsaturated fatty acids can alter the function of adipose tissue, while protecting the liver from insulin resistance and the accumulation of fat. They also elucidated possible mechanisms of action.

Genetically altered mice (prone to obesity, insulin resistance and fatty liver disease) were divided into four groups. One group was given an omega-3-enriched diet and the second group was given a control diet for a five week period. The third group was injected with the omega-3 fatty acid (DHA), and the fourth group received an injection of the omega-3 fatty acid-derived compound, resolvin. Blood and tissue samples were evaluated.

The omega-3-rich diet improved insulin tolerance and decreased inflammation. The key mechanisms by which the omega-3s exerted their beneficial impact included:

•    Up-regulating the genes involved in: insulin sensitivity, glucose transport and insulin receptor signaling.

•    Increasing adiponectin, the anti-inflammatory compound produced by fat cells, which also improves insulin sensitivity.

•    Creating protectins and resolvins, which offered a level of protection similar to that of rosiglitazone, a medication used to treat diabetes.

•    Blocking the formation of potent inflammatory compounds made from the omega-6 fatty acid, arachidonic acid.

Together the actions of omega-3 fats attenuated fatty liver, (hepatic steatosis).

Conclusion: These findings, together with evidence from other studies, provide a strong rationale for omega-3 supplementation for patients with liver disease.

Study Quote:"One of the most important findings of our study was that increased intake of omega-3-polyunsaturated fatty acids inhibited the formation of eicosanoids

derived from the omega-6-polyunsaturated fatty acids arachidonic acid."

Links:
Ana González-Périz, Raquel Horrillo, Natàlia Ferré, Karsten Gronert, Baiyan Dong, Eva Morán-Salvador, Esther Titos, Marcos Martínez-Clemente, Marta López-Parra, Vicente Arroyo, and Joan Clària.

Obesity-induced insulin resistance and hepatic steatosis are alleviated by -3 fatty acids: a role for resolvins and protectins

.FASEBJ Express 10.1096/fj.fj.08-125674, published online February 11, 2009.

Further Reading (Full Text Sources):
Hasturk H et al. ,
Resolvin E1 Regulates Inflammation at the Cellular and Tissue Level and Restores Tissue Homeostasis In Vivo. J Immunol 2007 179: 7021-7029

Serhan CN et al.
Resolution of inflammation: state of the art, definitions and terms FASEB J. (2007)21: 325-332.

Low Omega-6 Fat Diet Lowers Inflammation and Revs Up Fat Metabolism

2009-02-11T02:12:00Z

Bottomline: Healthy people were instructed to eat a diet low in omega-6 fatty acids and higher in omega-3 fats, which resulted in decreased inflammation, lower LDL-cholesterol, and increased fat metabolism in a small study lasting 10 weeks. Eur J Clin Nutr. 2008 Nov;62(11):1287-93.

Background:French researchers sought an effective, yet practical way to optimize dietary omega-3 fatty acids, via increased fish meals and lowering the intake of omega-6 polyunsaturated fatty acids. Ultimately, they wanted to know if this was achievable with "simple dietary advice" and if it resulted in health benefits--via cardiovascular risk factors and inflammation.

Summary: The diet trial lasted 10 weeks, which consisted of the following. Researchers instructed 17 healthy people to eat three fish meals per week (totaling of 300 grams or 9-ounces of fish per week) and to avoid foods containing high amounts of omega-6 polyunsaturated fatty acids. Vegetable oils were limited to olive oil and rapeseed/canola oil. The emphasis was placed on modifying what to eat, rather than quantities.
The effects of eating this diet were evaluated by measuring blood levels for their lipid, inflammatory, and hormonal profiles, as well as metabolism biomarkers.

There were beneficial changes indicated by a decrease in LDL-cholesterol, and increases of lipid oxidation and plasma adiponectin. Adiponectin is derived from fat cells (adipocytes), and is associated with protective metabolic and anti-inflammatory properties. Adiponectin may also up-regulate the genes involved in fat metabolism.

The researchers concluded that eating a low omega-6 fat diet with adequate omega-3 fatty acids, can be achieved with simple nutrition counseling, resulting in many health benefits effecting metabolism and inflammation. These encouraging results need to be confirmed and replicated with a larger group of people.

Study Quote:“…we were able to demonstrate that a simple dietary intervention markedly reduced the omega-6/omega-3 polyunsaturated fat ratio, assessed by both diet diary and erythrocyte membrane fatty acid concentration.”

Link to Study:
Guebre-Egziabher F, Rabasa-Lhoret R, Bonnet F, Bastard JP, Desage M, Skilton MR,Vidal H, Laville M.
Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr. 2008 Nov;62(11):1287-93.

Free Full Text Science Reviews: The Impact of Omega-6 and Omega-3 Fatty Acids on Health

2009-02-02T17:38:00Z

This list of free, full text, scientific reviews is updated regularly and compiled by Evelyn Tribole, MS, RD-- using the U.S. National Library of Medicine. These reviews explore the effect of the relationship between omega-6 and omega-3 fatty acids on various health conditions. Also, check out the side bar for the "Latest Omega-6 News", for newly published studies on omega-6 fats and links to the abstracts.

What is the American Heart Association’s Agenda? —It Sure Ain’t Science or Public Health

2009-01-30T20:13:00Z

Controversy and debate are an expected (and welcome) part of the scientific process. But the American Heart Association’s recent advisory urging Americans to gobble up their omega-6 fat is an unconscionable disservice, to both the scientific process and the public health.

Old School Cholesterol Dogma versus Science

On January 27, 2009 the American Heart Association (AHA) issued an advisory touting the benefits of eating plenty of omega-6 fats. Here's the problem--AHA made sweeping statements that are not supported by the research, while ignoring landmark studies, which don’t support their views [Harris]. While the cholesterol myth has finally been put to rest as the cause underlying heart disease (it's inflammation and beyond), it would seem that heart healthy eating would need some refinement.

Yet, the American Heart Association's key rationale for promoting omega-6 polyunsaturated fats, is because of their ability to lower blood cholesterol, when eaten in the place of saturated fats. (Keep in mind that one out of every two people with heart disease has a normal blood cholesterol level.) Furthermore, the AHA asserts that if Americans were to lower their current omega-6 fat, their heart health would suffer.

Omega-6 fat intake has sky-rocketed in the last century, so it would seem that we should see a dramatic lowering of heart disease in the USA, yes? No. The incidence of cardiovascular disease has increased in parallel with the increasein linoleic acid intakes in many countries [Ghosh]. Linoleic acid is the most commonly eaten omega-6 fatty acid. Notably, people who have died from heart disease have higher blood levels of the omega-6 fat, arachidonic acid, as shown below [Okuyama].

Do Countries with Low Omega-6 Fat Diets Have Higher Rates of Heart Disease?

Given the American Heart Associationn's rationale, we should see elevated heart disease in countries that eat diets low in omega-6 polyunsaturated fats. Nope, again. Think Mediterranean diet. Cultures that eat Mediterranean diets have much lower rates of heart disease.

Enter the Lyon Diet Heart study, a large intervention trial in which two groups of heart patients from France, were fed either a Mediterranean diet (low in omega-6 polyunsaturated fat) or a diet advocated by the American Heart Association, with indiscriminate use of polyunsaturated fats. The people eating the Mediterranean diet had a striking 70% reduction in all causes of death, including cancer, compared to the folks eating the "heart healthy diet".

While scientists have yet to agree, as to what officially defines the Mediterranean diet, most would agree that it is higher in monounsaturated fats and lower in polyunsaturated fats, which is synonymous with omega-6 fats. The dominate cooking oil used in these cultures is olive oil.

Olive Oil 101

The type of fat in Olive oil is mainly monounsaturated fatty acids. Nearly 75% of olive contains oleic acid, the monounsaturated fatty acid which is an omega-9 fat. Notably, olive is also low in both saturated fats and polyunsaturated fats. Here's the breakdown of olive compared to soybean oil. (Soybean oil is one of the top three sources of omega-6 fat in the American diet):

Key Studies Ignored:Evidence of Harm Beyond Inflammation

One of the most disturbing aspect of AHA's advisory is the complete disregard for studies published within the last five years, which demonstrate potential cardiac harm from eating the current status quo levels of omega-6 fats.

Severity of Atherosclerosis Associated with Dietary Omega-6 Fats. A study published in the New England Journal of Medicine evaluated the arteries of seemingly healthy people with a LOX genotype [Dwyer]. The scientists found an increase in the thickness of the carotid-artery intima–media, (which reflects atherosclerosis). Morever, increased dietary arachidonic acid significantly enhanced the apparent atherogenic effect of this genotype. Both dietary omega-6 fats, linoleic acid and arachidonic acid, were significantly associated with increased severity of atherosclerosis. The researchers concluded, “The observed diet–gene interactions further suggest that dietary n–6 polyunsaturated fatty acids promote, whereas marine n–3 fatty acids inhibit, leukotrienes-mediated inflammation that leads to atherosclerosis in this subpopulation.”

Tufts Scientists Say, "HighDietary PUFA n-6 May Not Result in Atherosclerosis Protection." The 2006 Framingham study by Tufts University scientists [Lai] investigated the effect of dietary omega-6 fats in people with a high risk of heart disease, because they have genetic mutation effecting lipoprotein( APOA5). Their findings showed that omega-6 fats, specifically, promoted the risk of atherosclerosis. The researchers concluded that for people with this genetic profile, "highdietary PUFA n-6 may not result in atherosclerosis protection." Notably, the subjects were eating a typical American diet, high in omega-6 fats.

Dietary Linoleic Acid (Omega-6 Fat) Increases Toxicity of LDL Cholesterol.A study on nearly 400 men in Finland [Louheranta] showed that as the amount of dietary linoleic acid (omega-6) increased, so did the oxidation of LDL which makes it more hazardous for heart health.

Canadian Study: Heart Benefits Are Not Achieved on Diets Rich in Omega-6 Fats “Our results also clearly raise the possibility that any positive effects of ALA [the omega-3 fatty acid found in plants, such as flax] are only realized when the diet is also low in linoleic acid , such as those found in intervention trials incorporating a Mediterranean diet high in monounsaturated fatty acids.” [Ghosh]. This animal study was designed to represent the differing and broad range of omega-6 and omega-3 fats in the human diet; and the impact on the heart. Their findings show that diets low in omega-6 fat, with high plant-based omega-3 fats, decreases the level of the potent omega-6 fat, arachidonic acid in the cell membranes of the heart. “An effect that is evident only when the diet also contains low levels of the omega-6 linoleic acid”. Furthermore, diets high in omega-6 fat influenced the enzymes in the heart responsible for increasing both inflammation and the availability of arachidonic acid.

The compelling results from these four studies, alone, raise the question of harm from eating excessive omega-6 fat on the heart. (And this by no means is an exhaustive review of the literature.)

Science Silo Mentality

You really can't be an expert of every field, especially in matters relating to diet and health. While I would not expect a heart scientist to be an expert on breast cancer, I would certainly hope that if heart experts are claiming that there is no harm from eating the current high levels of omega-6 fat, that they would use an inter-disciplinary approach to confirm their thinking. Sadly, that's not what happened.

Instead, we have a science silo mentality (a phrase coined by Bill Lands, PhD). In this situation, scientists work in their area of expertise, reaping their data, but without any of the necessary cross-talk with scientists in other fields.

Large studies from the USA, France and Sweden indicate a compelling link between high intakes of omega-6 fat and the development of breast cancer [Tribole.] For example, in a case-control study on nearly 1700 women, researchers demonstrated that women with a genotype inﬂuencing the LOX enzyme, had a two-fold increase in breast cancer risk if they ate high levels of the omega-6 fat, linoleic acid, and amount of 17.4g/day [Wang]. Yet, this genotype had no inﬂuence on breast cancer risk, if these women ate a lower linoleic acid diet. (For more details see,

Another New Breast Cancer Study: Omega-6 Fat Increases Risk Two-fold in Large U.S. Study).

The Omega-3 Fat Deficiency Gap

Another key factor, not taken into consideration is the gaping omega-3 fatty acid deficency in the American diet. The typical American eats only 85 of the 650 milligrams of the recommended omega-3 fatty acids (DHA + EPA). This is significant, because in the body, the omega-3 and omega-6 fats compete for the same enzymes to make their potent compounds. It's like a biological game of the "musical chairs", where there will always be a shortage--and in the case of fatty acids, the dominant fats "win" the enzyme.

No One is Suggesting the Elimination of Omega-6 Fat

In 1999, there was enough scientific evidence to prompt scientists to recommend an upper limit for omega-6 fats, to no more than 6.7 grams per day [Simopoulos]. This ceiling is based on eating a maximum of 3% fat calories from omega-6 fat on a 2000 calorie diet. (Note, this is a similar level to the the Lyon Diet Heart study.) Now, ten years later, the American Heart Association is urging people to continue to eat more than double that amount.

No scientist is urging for the elimination of omega-6 fats. Linoleic acid is the chief omega-6 fatty acid consumed by Americans and westernized countries, and it is essential but in small quantities. This is similar to the nutrient sodium, it's essential in small amounts, but in excess it's not good for your health.

When the dietary omega-3 and omega-6 fats are in balance, it's truly a beautiful synergy in the body. But in excess, the omega-6 fatty acids are like overzealous fire-fighters, chopping down your door because of a chronic false fire alarm. Yes, we need fire departments and fire fighters, but if they destroy the very buildings they are trying to protect, it's a problem--akin to chronic inflammation in the body, which lies at the root of many diseases.

To advocate for the status quo, when there is evidence of harm is unconscionable--especially when lowering omega-6 fats to a more balanced level is clearly NOT harmful to health.

Links to Sources

American Heart Asssociation News Release. Omega-6 fatty acids: Make them a part of heart-healthy eating DALLAS, Jan. 27, 2009.

de Lorgeril M et al. Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction : Final Report of the Lyon Diet Heart Study Circulation1999;99:779-785 (Free full text)

Dwyer, James H., Allayee, Hooman, Dwyer, Kathleen M., Fan, Jing, Wu, Huiyun, Mar, Rebecca, Lusis, Aldons J., Mehrabian, Margarete.Arachidonate 5-Lipoxygenase Promoter Genotype, Dietary Arachidonic Acid, and Atherosclerosis. N Engl J Med 2004 350: 29-37.

Ghosh S, Novak EM, and Innis, SM. Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 -linolenic acid ratios in normal, fat-fed pigs. Am J Physiol Heart Circ Physiol (2007)293: H2919-H2927, Free Full Text.

Harris WS et al. 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. Circulation published January 26, 2009,. Free Full Text. doi:10.1161/CIRCULATIONAHA.108.191627.

Hibbeln, Joseph R, Nieminen, Levi RG, Blasbalg, Tanya L, Riggs, Jessica A, Lands, William EM. Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity.Am J Clin Nutr 2006 83: S1483-1493. Free Full Text.

Lai CQ et al.Dietary Intake of n-6 Fatty Acids Modulates Effect of Apolipoprotein A5 Gene on Plasma Fasting Triglycerides,Remnant Lipoprotein Concentrations, and Lipoprotein Particle Size: The Framingham Heart Study.Circulation (2006)113: 2062-2070. Free Full Text.

Lands WE.Dietary fat and health: the evidence and the politics of prevention: careful use 
of dietary fats can improve life and prevent disease. Ann N Y Acad Sci. 2005 Dec;1055:179-92.

Leaf A.Dietary Prevention of Coronary Heart Disease:The Lyon Diet Heart Study.Circulation 1999;99:733-735. Free Full Text.Circulation 1999;99:733-735. Free Full Text.Circulation 1999;99:733-735. Free Full Text.

Louheranta, AM, Porkkala-Sarataho, EK, Nyyssonen, MK, Salonen, RM, Salonen, JT. Linoleic acid intake and susceptibility of very-low-density and low
density lipoproteins to oxidation in men. Am J Clin Nutr 1996 63: 698-703.

Okuyama. H. Prevention of Coronary Heart Disease From the Cholesterol Hypothesis to omega-6/omega- 3 Balance. World Review of Nutrition and Dietetics (2007)Vol. 96:1-158.

Ramsden CE, Hibbeln JR, Lands WE. Letter to the Editor re: Linoleic acid and coronary heart disease.Prostaglandins Leukot Essent Fatty Acids. 2009 Jan 13.PMID: 19147338

Simopoulos AP.The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease 
and other chronic diseases.Exp Biol Med (Maywood). 2008 Jun;233(6):674-88.Free Full Text.

Simopoulos, AP, Leaf A, and Salem N. Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids.
J Am Coll Nutr 1999 18: 487-489. (free full text)

Tribole, E..What happened to do no harm? The issue of dietary omega-6 fatty acids.Prostaglandins Leukot Essent Fatty Acids. 2009 Jan 13. [Epub ahead of print] . PMID: 19147337

Wang J et al. 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein Gene Polymorphisms, Dietary Linoleic Acid, and Risk for Breast Cancer.

Cancer Epidemiol Biomarkers Prev October 1, 2008(17): 2748-2754

How Much Arachidonic Acid in Meats and Poultry? The Free Omega-6 Fat Tracker Widget

2009-01-19T20:30:00Z

The Omega-6 Fat Tracker--(Arachidonic Acid in Meats & Poultry) lists the amount of arachidonic acid (the most potent omega-6 fatty acid) in beef, veal, sausage, lamb, wild meats, chicken, eggs, and turkey.

I created this widget and I'm giving it away. Yes, free, no strings attached (a credit line would be nice, but not required).

Why? I want to increase awareness of the health issues created from excess dietary omega-6 fats, the most commonly eaten polyunsaturated fat in westernized countries.

Get It: At the very bottom of the chart, click "" and it's yours. (If you want to place it on your blog or website)

Use It: You can sort the columns, just as you would in an Excel spreadsheet. (Also, check out the Omega-6 Fat Tracker for oils, located on right, sidebar toward the bottom.)

Improve It: I plan to create more Omega-6 Fat Trackers for other food categories. Drop me an email/comment as to which foods or categories that you'dlike see an Omega-6 Fat Tracker created. (I've appreciated your helpful comments on the vegetable oil widget).

Omega-6 Fat: The Polyunsaturated Fat Paradox in Heart Disease and Inflammation

2009-01-15T07:10:00Z

A Mediterranean diet is more than drizzling olive oil on your salad---it’s low in omega-6 fat, a key point neglected in Jane Brody’s New York Times column this week. Brody correctly pointed out that Inflammation is the pivotal cause underlying heart disease (in fact, inflammation was declared as one of the 10 Medical Breakthroughs for 2008 by Time magazine.)

Inflammation is the "new cholesterol" in matters of eating to protect the heart (and other chronic diseases for that matter). Notably many inflammation medications work by blocking the effects of excess omega-6 fat, including statins, aspirin, and asthma inhalers. (See Medications that Block Effects of Omega-6 Fat)

Brody explains in her column, how the landmark Lyon Diet Heart study diet trumped the American Heart Association diet for reducing death rates from all-causes, including cardiac death and cancer.

Here's the glitch. A hallmark feature of the Lyon Diet is its low omega-6 fat content, because it was patterned after the diet eaten by the inhabitants from the Greek island of Crete (they have one of the lowest rates of heart disease). Therefore the researchers limited the omega-6 fat content to 4% of calories, which is about 7 grams/day (that’s about the amount in one tablespoon of soybean oil).

Just last month, the lead scientists of the Lyon Diet Heart study chastised researchers for ignoring the omega-6 factor, "...the epidemiologists does not capture one major lipid characteristic of the Mediterranean diet, which is actually low in omega-6”. (See The Mediterranean Diet is Low in Omega-6 Fat, Say Lyon Diet Heart Study Scientists)

Ironically, omega-6 fats are the same polyunsaturated fats, touted indiscriminately, for years by the American Heart Association, for heart health. (While polyunsaturated fats technically consist of both omega-6 fats and omega-3 fats, our diets are in very short supply of omega-3 fats.) Therefore it was no accident that the folks relegated to eating the American Heart Association diet, did not fare well compared to those eating the Lyon Diet.

In 1999, there was enough scientific evidence to prompt scientists to recommend an upper limit for omega-6 fats, to no more than 6.7 grams per day. This ceiling is based on eating a maximum of 3% fat calories from omega-6 fat on a 2000 calorie diet. (Note, this is similar to the the Lyon Diet Heart study.) Here we are ten years later, and many people have not heard of omega-6 fat, or they assume any “omega fat” is associated with health benefits. Not so.

What’s the Harm? The Polyunsaturated Fat Paradox

Cultures that suddenly increase their polyunsaturated fat intake (which is synonymous with omega-6 fat) experience markedly health problems. When the inhabitants of Okinawa tripled their omega-6 fat intake, they experienced a rise in cancer and cardiovascular disease, which Japanese researchers called “excess linoleic acid syndrome”. (Linoleic acid is the common chemical name for the plant-based omega-6 fat.)

Israel embraced eating a high polyunsaturated fat diet (at the expense of saturated fats), and achieved one of the highest omega-6 fat intakes in the world. Consequently, they also experienced an unexpected high incidence of chronic western diseases, which researchers term the “Israeli paradox”.

Greenland Inuit Eskimos are famous for their high omega-3 fat diet, but just as importantly, their diet was also low in omega-6 fat.

Omega-6 fats are the most commonly eaten polyunsaturated fat in westernized countries. Prior to industrialization, no population has been exposed to the current high levels of omega-6 polyunsaturated fats. We evolved on a diet with a balanced proportion of omega-6 to omega-3 fats of about 1:1. Today, that ratio in westernized countries is out of whack, near 20:1 of omega-6 to omega-3 fats.

Different farming practices, new food processing and the urging by health authorities to use vegetable oils in place of animal fats--triggered an onslaught of omega-6 fats into the food we eat. Consider that today:

We eat oils that did not exist 100 years ago, like cottonseed oil, which is one of the top three sources of omega-6 fat in the American diet (along with soybean oil and corn oil).

Most cattle no longer graze in pastures, they eat feedlot-cuisine of corn, which is high in omega-6 fat. The longer a cow grazes in the pasture, the lower the omega-6 fat content of its meat and milk.

How to Lower Omega-6 Fat
Fortunately, eating a lower omega-6 fat diet is very doable—if you know what to look for. You won’t find “omega-6 fat” on the Nutrition Facts list, because it’s not required on the food label.

You’ll need to turn to the ingredient list and check for one of these top sources of omega-6 fat: soybean oil, corn oil, cottonseed oil, safflower oil or sunflower oil. Especially, check the ingredients in your margarine, mayonnaise and salad dressing---and you’ll likely find one of those oils (or “vegetable oil”, which is typically a soybean oil blend).

You can also use the Omega-6 Fat Tracker widget to help you identify sources of omega-6 fat in oils. If you are vegetarian or a health-conscious eater, you are not off the hook, as these foods tend to be especially high in omega-6 fat.

Yes, it's time to say goodbye to the dogma of polyunsaturated-fats-are-heart-healthy.

Sources:
Cordain, L et al. Origins and evolution of the Western diet: health implications for the 21st century.
American Journal of Clinical Nutrition (2005).81:341-354. FREE FULL TEXT

de Lorgeril M et al.
Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction : Final Report of the Lyon Diet Heart Study.
Circulation1999;99:779-785 (Free full text)

Dubnov G. and Berry EM.
Omega-6/omega-3 fatty acid ratio: The Israeli Paradox.
World Review of Nutrition and Dietetics. (2003):92:81-91.

Hibbeln, Joseph R, Nieminen, Levi RG, Blasbalg, Tanya L, Riggs, Jessica A, Lands, William EM
Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity
Am J Clin Nutr 2006 83: S1483-1493. (Free Full Text)Am J Clin Nutr 2006 83: S1483-1493. (Free Full Text)

Lands WEM.
Dietary fat and health: the evidence and the politics of prevention.
Annal New York Academy of Sciences (2005). 1055:179-192.

Leaf A.
Dietary Prevention of Coronary Heart Disease:Final Report of the Lyon Diet Heart Study.
Circulation 1999;99:733-735 (Free full text)

Okuyama, H et al.
Dietary fatty acids—the n-6/n-3 balance and chronic elderly diseases: excess linoleic acic and relative n-3 deficiency syndrome seen in Japan.
Prog. Lipid. Res (1996); 35(4):409-457.

Okuyama H, Ichikawa Y, Sun Y, Hamazaki T, Lands W.
Omega-3 Fatty Acids Effectively Prevent Coronary Heart Disease and Other Late-Onset Diseases – The Excessive Linoleic Acid Syndrome.
World Rev Nutr Diet. Basel, Karger, 2007, vol 96, pp 83-103 (DOI: 10.1159/000097809)

Simopoulos, Artemis P.
The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases

Experimental Biology and Medicine 2008 233: 674-688 Free Full Text.

Simopoulos, Artemis P., Leaf, Alexander, Salem, Norman, Jr
Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids.
J Am Coll Nutr 1999 18: 487-489. (free full text)

.

How Much Omega-6 in Vegetable Oils? The Omega-6 Fat Tracker Widget

2009-01-12T02:09:00Z

Bottomline: Omega-6 Fat Tracker is a free widget that lists the omega-6 fatty acid content in vegetable oils.

The Omega-6 Fat Tracker-Oils lists the amount of omega-6 fat in oils, per tablespoon. I created this widget and I'm giving it away. Yes, free, no strings attached (a credit line would be nice, but not required).

Why? I want to increase awareness of the health issues created from excess dietary omega-6 fats, the most commonly eaten polyunsaturated fat in westernized countries.

Get It: At the very bottom of the chart, click "" and it's yours. (If you want to place it on your blog or website)

Use It: You can sort the columns, just as you would in an Excel spreadsheet.

Improve It: I plan to create other Omega-6 Fat Trackers for other food categories. Drop me an email/comment as to which foods or categories that you'd like see an Omega-6 Fat Tracker created.

Note for Omega-6 Fat Tracker-Oils: Since these are plants-based oils, the omega-6 fatty acid is linoleic acid, which is listed in milligrams. Keep in mind that experts recommend no more than 6700 milligrams of omega-6 fat per day for adults, see: How Much Omega-6 Fat is Too Much?

Acne: Omega-6 Fat Worsens Skin Inflammation

2009-01-08T19:21:00Z

Bottomline: Acne is an inflammation disorder involving omega-6 fats.

Background: Acne is more than an awkward right of passage for teens and the hormonally-challenged (think menopause), it is an inflammation disorder of the skin, which involves the same inflammatory compounds triggered by asthma, clogged arteries and possibly breast cancer.

It was not that long ago that scientists started to explore the role of omega-6 fats and their inflammatory compounds in acne. It was only in 2005 that researchers (Iwata), examined the sebaceous gland—the cornerstone of acne folly, in hamsters (hard to imagine) and identified the presence omega-6 fat compounds.

First Human Study
One year later, in 2006, a researcher team (Alestas) compared the skin cells of healthy people with those afflicted with acne. The acne group,had two different areas of skin cells evaluated--one section from the outbreak area and the other cells were from an uninvolved area of their skin.

The findings were profound—as it was the first acne study to identify several omega-6 fat compounds that worsen inflammation in humans. They also found key enzymes, which turn omega-6 fat into potent incendiary compounds in the skin.

Look at the picture below, which compares the skin cells of healthy people with skin cells of people afflicted with acne. You don’t need to be a scientist to see the startlingly difference--the red color shows inflammation with the 5-LOX enzyme present.

The redness reflects the amount of a key enzyme, 5-LOX, which turns the omega-6 fat, arachidonic acid, into potent leukotrienes, a group of inflammatory compounds associated with breast cancer, heart disease and asthma. (See these links for more detail):

Asthma Triggering Compounds from Omega-6 Fat Create Clogged Arteries,

Arachidonic Acid Gone Awry—Increases Risk of Heart Attack

Another New Breast Cancer Study: Omega-6 Fat Increases Risk Two-fold in Large U.S. Study

The Asthma-Acne Link
Interestingly, in 2005 doctors reported a case study in which a 40-year old woman with acne was treated successfully with the asthma medication, Zileuton, which is a leukotrienes-inhibitor. But when she stopped using the medication her skin problem resumed.

Many of the active ingredients in topical acne and blemish creams and medications work by blocking the inflammatory effects of omega-6 fats (Mackowiak). For example, salicylic acid, a form of aspirin, works by blocking the COX enzymes, which prevents omega-6 fats from churning out inflammatory compounds (these enzymes are also elevated in people with acne).

Hunter-Gatherers--No Such Thing as Acne

“Not a single papule, pustule, or open comedone was observed in the entire population examined.”

Acne and chronic inflammatory diseases, like stroke and heart attacks, were nonexistent in hunter-gather tribes (Cordain). Yet the incidence of acne in westernized countries reaches over 95% over a person's lifetime. It is our diets that have dramatically changed over the last century—we eat foods that increase inflammation in our bodies.

Omega-6 Fat Diet Connection
The more omega-6 fats in your diet, the more inflammatory arsenal lines your cells, whether it’s the cells of your skin or lungs. Dietary omega-6 and omega-3 fats compete for limited seating in the cells. Whichever fat is in most abundant supply in your diet, gets the coveted cellular seat, like competition for open seating at a sold-out concert.

In the case of the American diet, omega-6 fat “wins” a great majority of the cell's selective seating, as part of a phospholipid, which means more fuel for inflammation. No culture has ever been exposed to the current high levels of omega-6 fat in the diet, in part because it wasn’t possible 100 years ago, before technology.

Our ancestors ate a diet of equal proportions of omega-6 and omega-3 fats. Today, that balance is out of whack--omega-6 fats outnumber omega-3 fats by 10 to 20-fold. Omega-6 fats are the most common polyunsaturated fat eaten.

The top sources of omega-6s are soybean oil, corn oil, vegetable oil and cottonseed oil, which are chief ingredients in margarine, salad dressings, mayonnaise, processed foods and many so-called "heart-healthy" foods. For more information see

Foods High in Omega-6 Fat and Inflammation 911 Podcast: The Role of Omega-6 Fats.

Links to Sources:
Alestas T, Ganceviciene R, Fimmel S, Müller-Decker K, Zouboulis CC.
Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands.
J Mol Med. 2006 Jan;84(1):75-87. Epub 2005 Dec 31.

Cordain, L. et al.
Acne Vulgaris: A Disease of Western Civilization.
Archives of Dermatology, 2002;138:1584-1590. FREE FULL TEXT

Iwata C, Noriko Akimoto1, Takashi Sato, Yuki Morokuma and Akira Ito
Augmentation of Lipogenesis by 15-Deoxy-[Delta]12,14-Prostaglandin J2 in Hamster Sebaceous Glands: Identification of Cytochrome P-450-mediated 15-Deoxy-[Delta]12,14-Prostaglandin J2 Production.
J Investig Dermatol (25 Oct 2005)125 (5):865-72 FREE FULL TEXT.

Logan A.C.
Linoleic and linolenic acids and acne vulgaris
British Journal of Dermatology (2008)Volume 158, Issue 1:201–202. FREE FULL TEXT.
http://www3.interscience.wiley.com/cgi-bin/fulltext/119388273/HTMLSTART

Mackowiak PA
A brief history of antipyretic therapy.

Clinical Infectious Diseases 2000 31:s5, S154-S156. FREE FULL TEXT.

Zhang Q et al.
Involvement of PPAR[gamma] in Oxidative Stress-Mediated Prostaglandin E2 Production in SZ95 Human Sebaceous Gland Cells,
J Invest Dermatol (2006)126 (1), 42-44.

Zouboulis C
Sebaceous Glands and the Prostaglandin Pathway--Key Stones of an Exciting Mosaic

J Investig Dermatol (Nov 2005)125 (5), FREE FULL TEXT.
http://www.nature.com/jid/journal/v125/n5/abs/5603596a.html

Zouboulis CC, Jens Malte Baron, Markus Böhm , Stefan Kippenberger, Hjalmar Kurzen, Jörg Reichrath and Anja Thielitz.
Frontiers in sebaceous gland biology and pathology
Experimental Dermatology (2008)Volume 17( 6):542–551 FREE FULL TEXT

Zouboulis ChC, Saborowski A, Boschnakow A.
Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.
Dermatology. 2005;210(1):36-8.

Seed Newsvine

Omega-6 Fat Increases Asthma Risk in Kids

2009-01-02T00:09:00Z

Bottomline: A study on over 25,000 school-aged kids shows eating higher amounts of the omega-6 fatty acid, linoleic acid, increased risk of asthma. Clin Exp Allergy. 2008 Oct;38(10):1644-50.

Background: There is a worldwide rapid rise in the prevalence of asthma which is not explained by genetics. Different studies on children in Italy, Spain, Greece and Australia have implicated the increase of dietary omega-6 fats as a possible reason for increased asthma or wheezing. When the omega-6 fat, arachidonic acid combines with the LOX enzyme, it creates one of the most potent compounds that wreak inflammation havoc on the lungs, the leukotriene B4.

Summary: Dietary habits of over 25, 000 children from Okinawa, Japan were evaluated over a period of one month using a food frequency assessment. Symptoms of wheeze and asthma were evaluated according to diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Intake of linoleic acid was independently associated with an increased prevalence of wheeze after allowance for confounding factors.

The results of this study are consistent with findings from other researcher. For example, Eating margarine (a food high in omega-6 fat) was significantly related to the prevalence of wheeze among Italian children. A nested case-control study among Australian children showed a significant association between the prevalence of omega-6 fat in the diet and the risk of asthma.

Comment: Notably, this population of kids in Japan, eat a high fish diet, rich in omega-3 fats. A recent study (Castro-Rodguez), showed that a Mediterranean diet, which is typically low in omega-6 fat, was protective against wheezing, independent of physical activity and obesity.

Links to Studies:
Castro-Rodriguez JA et al.
Mediterranean Diet as a Protective Factor for Wheezing in Preschool Children.

J Pediatr 2008;152:823-828.

Miyake Y, Sasaki S, Arakawa M, Tanaka K, Murakami K, Ohya Y.
Fatty acid intake and asthma symptoms in Japanese children: the Ryukyus Child Health Study.
Clin Exp Allergy. 2008 Oct;38(10):1644-50.

Oddy WH, de Klerk NH, Kendall GE, Mihrshahi S, Peat JK.
Ratio of omega-6 to omega-3 fatty acids and childhood asthma. J Asthma. 2004;41(3):319-26.

Seed Newsvine

Polyunsaturated Fats Dull Cognitive Performance with Age

2008-12-23T05:35:00Z

Bottomline: Consuming seed oils, high in omega-6 polyunsaturated fatty acids, is associated with cognitive impairment in older people according to results of Greek epidemiological study.

Public Health Nutr. 2008 Oct;11(10):1054-62

Background: The prevalence of cognitive impairment is increasing, with dementia being its most severe form. Since Alzheimer’s disease is the most frequent cause of dementia and is associated with many chronic diseases and lifestyle factors, the researchers evaluated diet and lifestyle factors that play a possible role in both conditions.

Summary: Researchers evaluated diet and cognitive capacity of 732 Greek men and women, aged 60 years or older. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function and is considered good indicator of a person’s mental capacity for everyday activities. Diet was evaluated using a food frequency questionnaire including approximately 150 foods and beverages commonly consumed in Greece.

The researchers found that polyunsaturated fatty acid intake was associated with poorer cognitive performance scores. A similar inverse association was observed with consuming seed oils, which contain a high amount of the omega-6 fatty acid, linoleic acid. This is consistent with results from the Zutphen Elderly Study, which showed that high linoleic acid intake was associated with cognitive impairment.

Study Quote: "At this stage, it would be fair to conclude that long-chain omega-3 fatty acids are possibly beneficial, whereas omega-6 fatty acids may have an adverse effect on cognitive performance."

Comment: While this study does not specify which seed oils were associated with cognitive decline, researcher, Andreas Kyroziswas, responded to my email query, and indicated that "corn oil, sunflower oil and soybean oil are the seed oils mostly consumed in Greece." Notably, this is similar to the USA--soybean oil and corn oil are among the top contributors of omega-6 fat in the American diet. Also, recent studies have shown that the omega-6 fatty acid, arachidonic acid, is elevated in Alzheimer's disease (See Brain Image Study Shows Increased Arachidonic Acid in Alzheimer's Patients)

Link to Study:
Psaltopoulou T, Kyrozis A, Stathopoulos P, Trichopoulos D, Vassilopoulos D, Trichopoulou A. Diet, physical activity and cognitive impairment among elders: the EPIC-Greececohort (European Prospective Investigation into Cancer and Nutrition)..Public Health Nutr. 2008 Oct;11(10):1054-62. Epub 2008 Jan 21.

Seed Newsvine

Inflammation—Omega-6 Link Between Depression and Heart Disease

2008-12-15T18:01:00Z

Bottomline: Depressed patients had significantly elevated arachidonic acid and inflammation biomarkers. Notably, depressed patients who were unresponsive to medication, had a markedly low EPA to arachidonic acid ratio in their blood. J Psychiatric Res (2008), doi:10.1016/j.jpsychires.2008.06.003.

Background: While there are several anti-depressant medications used to treat major depressive disorder, a significant amount of patients will not respond to medication (non-responders). Previous studies show that inflammation may be a contributing factor to medication failure.

Summary: Researchers evaluated plasma levels of fatty acids and inflammation biomarkers in three groups of people: 20 depressed patients who did not respond to medication; 14 depressed patients who responded to medication; and 24 healthy controls. All of the patients met the diagnostic criteria for major depressive disorder. The antidepressant medications used were selective serotonin reuptake inhibitors (SSRIs).

Both groups of depressed patients had significantly higher levels of arachidonic acid and pro-inflammatory cytokine interleukin-6, compared to healthy controls. Furthermore, patients who did not respond to medication had a lower EPA to arachidonic acid ratio, which suggests a skewing of the balance between omega-3 to omega-6 fatty acids. The data are indicative of a pro-inflammatory state in major depression with activation of the arachidonic acid cascade. Notably, the inflammation state persists even when mood is returned to normal from treatment with anti-depressant medication.

Study Quote: “...major depression is associated with a high omega-6 to omega-3 ratio and elevation in the cytokine interleukin-6. Depression significantly increases the risk of cardiovascular disease and the present data may be relevant in explaining the link.”

Comment: A random-double-blind control study on 60 patients (Jazayeri et al) showed that EPA alone was comparable to using the antidepressant, fluoxetine (prozac) for treating depression. (Fluoxetine is a selective serotonin reuptake inhibitor, SSRI.)

Furthermore, there was a superior impact when both EPA and fluoxetine were used together, reflected by improvement in symptoms using the Hamilton Depression Rating Scale. While the researchers did not measure blood levels, they theorized that the synergistic effect was from EPA’s ability to lower pro-inflammatory cytokines. Notably, cytokines can also lower serotonin production.

The American Psychiatric Association recommends that patients with mood disorders take at least one gram of omega-3 fatty acids in the form of DHA + EPA, the type found in fish (Freeman et al).

Links to Sources:
Dinan T, Siggins L, Scully P, O'Brien S, Ross P, Stanton C.
Investigating the inflammatory phenotype of major depression: Focus on cytokines and polyunsaturated fatty acids. Journal of Psychiatric Research (2008), doi:10.1016/j.jpsychires.2008.06.003.

Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL.
Omega-3 fatty acids: evidence basis for treatment and future research in
psychiatry. J Clin Psychiatry. 2006 Dec;67(12):1954-67.

Jazayeri, S, Tehrani-Doost M, Keshavarz SA., Hosseini M, Abolghassem, Amini, Homayoun, Jalali, Mahmoud & Peet, Malcolm (2008). Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Australian and New Zealand Journal of Psychiatry, 2008 42 (3), 192-198. Retrieved December 15, 2008, from www.informaworld.com/10.1080/00048670701827275. style="background: gray none repeat scroll 0% 0%; overflow: auto ! important; position: absolute; left: 0px; top: 278px; width: 5px; height: 100%; z-index: 10000000; -moz-background-clip: -moz-initial; -moz-background-origin: -moz-initial; -moz-background-inline-policy: -moz-initial; opacity: 0; font-weight: bold ! important; font-size: medium ! important; font-style: normal ! important;" id="hwContLayer">

Linoleic Acid Ups Glucose Production--Possible Link of Omega-6 Fat to Type 2 Diabetes

2008-12-09T18:26:00Z

Bottomline: Linoleic acid Increases glucose production in a dose-dependent manner, which may be a key mechanism in the progression of Type II diabetes in obese people. Am J Physiol Cell Physiol 295: C1518-C1527, 2008Am J Physiol Cell Physiol 295: C1518-C1527, 2008.

Background: Free fatty acid levels are often increased in obese individuals and have been implicated in the progression of obesity to type II diabetes. The liver plays a major role in regulating glucose levels by making, storing and releasing glucose in the blood. Fatty acids have been proposed to directly influence gluconeogenesis in the liver, independent of hormones. But the components of the signaling cascade have not been systemically investigated and until this study, remained largely unknown. Linoleic acid is the most abundant polyunsaturated fatty acid in the diet.

Study: Scientists evaluated the effect of fatty acids on specific enzymes and transcription factors effecting glucose metabolism in liver cells. Linoleic acid increased glucose production in a dose dependent manner, through its effect on several pathways. There was an increase of the enzymes COX-2, cytosolic phospholipase A2 (cPLA2) and an increase in transcription factors. The researchers proposed the following mechanism, illustrated below, whereby linoleic acid triggers a calcium influx and cPLA₂, which stimulates arachidonic release, COX-2 activation, and PGE₂ production. Linoleic acid also activates transcription factors, which subsequently increase gluconeogenic enzymes, ultimately increasing glucose production:

Study Quote: “Linoleic acid also acts through membrane lipids, as ligands for receptors and transcription factors that regulate gene expression, as precursor for eicosanoids, in cellular communication, and through direct interactions with proteins.”

Comment: This study adds another layer of concern about eating excessive omega-6 fats; because linoleic acid was shown to directly trigger many biological responses. One of the key concerns of eating excessive linoleic acid has been that it competes with the enzymes needed to make the potent omega-3 fatty acids, (EPA and DHA), which is akin to a biological game of musical chairs. Except rather than grabbing for limited chairs, the omega-6 and omega-3 fatty acids vie for limited enzymes. When linoleic acid “wins” it uses the enzymes to make arachidonic acid, which is a key player in many inflammatory responses leading to chronic diseases from cancer to heart disease.

Link to Study:
Han Na Suh, Huang Thi Huong, Chang Hun Song, Jang Hern Lee, and Ho Jae Han.
Linoleic acid stimulates gluconeogenesis via Ca²⁺/PLC, cPLA₂, and PPAR pathways through GPR40 in primary cultured chicken hepatocytes .Am J Physiol Cell Physiol 295: C1518-C1527, 2008Am J Physiol Cell Physiol 295: C1518-C1527, 2008. First published doi:10.1152/ajpcell.00368.2008

Mothers Eating Diets High in Omega 6 Fats May Increase Risk of Breast Cancer

2008-11-22T00:22:00Z

Bottomline: A diet high in omega-6 fat eaten during pregnancy may increase the baby’s risk for developing breast cancer, according to results of a study presented at the American Association for Cancer Research's Seventh Annual International Conference on November 18, 2008.

Background: In the 1950s and 1960s, doctors started to recommend increasing polyunsaturated fats to reduce the risk of heart disease. Notably, omega-6 fats are the most common and dominant polyunsaturated fat in the USA. “Soon after those recommendations is when hormonally-influenced cancers - prostate, breast, colon - started going up," according to Dr. Elaine Hardman, Ph.D., associate professor of biochemistry and microbiology at Marshall University School of Medicine and lead author of the study.

Summary: Hardman’s research team fed one group of pregnant mice a diet containing corn oil. Corn oil was used to evaluate the risk of developing breast cancer, because of it’s high omega-6 fat content and it reflects the omega-6 fat content of the American diet. The other group was fed a canola oil based diet. Canola oil was used because of its lower omega-6 fat content and its availability. After weaning, all offspring were fed a diet containing corn oil. Next the incidence of breast cancer and changes to breast cancer regulating genes in the offspring were evaluated.

While both groups of offspring were about the same weight, the total tumor weight, number of glands with tumors and fraction of mice with tumors were higher in those whose mothers who were fed corn oil. The researchers found changes in gene expression up to five months after the animals were exposed to a diet containing omega 6 fatty acids during gestation and lactation.

Hardman theorizes that during gestation and lactation, the mother's diet must be imprinting the genes of the baby. The canola oil group displayed up-regulated genes and transcription factors that influence tumor suppression.

Scientist Quote: "This is a slam-dunk easy change for people to make," said Hardman. "Canola oil is readily available on the grocery shelf, doesn't cost any more than corn oil, and we can use it for all the things we use corn oil. It will help correct some of the omega 3 and omega 6 imbalance. And by changing the mother's diet, we might be able to reduce cancer in the next generation."

Comments: These results demonstrate new mechanisms by which omega-6 fats may promote breast cancer--a nutrient gene interaction. These findings are also consistent with two human studies. See:

Omega-6 Fat May Promote Breast Cancer Development

Another New Breast Cancer Study: Omega-6 Fat Increases Risk Two-fold in Large U.S. Study).

While canola oil is much lower in omega-6 fat than corn oil (See Foods High in Omega-6 Fat)

, you can lower omega-6 fat even further by switching to olive oil, for use in cooking, marinades and salad dressing. Olive oil has half the amount of omega-6 fat compared to canola oil--1320 versus 2840 milligrams, per tablespoon, respectively.

Sources:
American Association for Cancer Research's Seventh Annual International Conference.

Arachidonic Acid Gone Awry—Increases Risk of Heart Attack

2008-11-19T05:13:00Z

Bottomline: People with a genetic disposition have a greater risk of having a heart attack if they eat a diet high in arachidonic acid, which is found in animal foods such as meats and eggs.
Am J Clin Nutr 2008 88: 934-940

Background: The leukotrienes, are a group of eicosanoids that include one of the most potent inflammatory compounds made from arachidonic acid. Leukotrienes are well known for their inflammation effect on asthma and have recently been linked to atherosclerosis. A previous study from this group showed that people possessing a genetic polymorphism, which created more leukotrienes, also had an increased risk of clogged arteries when eating a high omega-6 diet (the classic American diet). To build on that research, the scientists evaluated if this genetic disposition, combined with a high omega-6 fat diet, would lead to more heart attacks.

Summary: In this case-control study, researchers identified nearly 2000 Costa Ricans, that possessed a gene that increases leukotriene formation from arachidonic acid. (Specifically, this gene increases the activity of the LOX enzyme, which is necessary for this step to occur).

Next, they evaluated incidence of heart attacks in people with the LOX polymorphism. Indeed, there was an increased risk of having a heart attack in this group of people, if they ate a high arachidonic acid diet (of at least 250 milligrams of arachidonic acid per day).

Interestingly, if the diet was lower in arachidonic acid, there was a protective effect-- a phenomenon that was observed in a previous study. The researchers believe that people with this polymorphism are sensitive to substrate availability. Therefore this type of gene could possibly be down or up-regulated, on the basis of cellular arachidonic acid concentrations. This gene-nutrient interaction replicates previous results with a more clinically relevant endpoint, heart attack events.

Study Quote: “These results are consistent with the notion that certain persons could benefit more from certain dietary modifications, such as a reduction in the intake of beef and eggs (major sources of arachidonic acid)…”

Comment:
These findings are similar to a recent study, in which women with another kind of LOX polymorphism had an increase incidence of breast cancer if they ate a high omega-6 fat diet. Yet the risk disappeared if they ate a lower omega-6 fat diet.(See Another New Breast Cancer Study: Omega-6 Fat Increases Risk Two-fold in Large U.S. Study).

To put into context what 250 milligrams of arachidonic acid looks like, consider these amounts of arachidonic acid found in food:

3-ounces chicken thigh (skinless, cooked) has 120 milligrams
3-ounces dark turkey meat (skinless, cooked) has 240 milligrams
3-ounces ham has 70 milligrams
3-ounces veal (cooked) has 90 milligrams
1-large egg has 70 milligrams
6-piece Chicken McNuggets has 50 milligrams
1-classic double cheeseburger (Wendy's) has 90 milligrams

Link to Source:
Allayee, H et al.
Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction Am J Clin Nutr 2008 88: 934-940

Not So Fast--- Statins vs Mediterranean Diet

2008-11-13T02:36:00Z

Bottomline: What you eat can be an effective way to lower heart disease and improve health---without the risks from taking statin medications.

Commentary

There’s been a lot of buzz about the JUPITER study, (1), which showed that statins lower the inflammatory marker, high-sensitivity C-reactive protein (CRP) in healthy patients, and prevented heart attacks, strokes and deaths. Yet, there are compelling studies, which show that diet reduces CRP, prevents heart disease and death (but there’s not much hoopla, even though the data exist!) We need to consider the powerful impact of diet as a means of primary disease prevention in healthy people, before popping statin pills as the first line of defense.

Portfolio Diet Just as Effective as a Statin
The Portfolio Diet (a diet high in soluble fiber) went head-to-head with a statin and was shown to be just as effective as a statin in lowering cholesterol and CRP in men and women with high cholesterol. (Jenkins)

Healthy Diet Reduce CRP’s by 41%
Healthy women who scored high on the Alternate Eating Index had a 41% reduction in CRP’s. This index reflects core components reflecting a healthy diet, associated with disease prevention (Fargnoli).

Lyon Diet Reduced All-Cause Mortality
Let’s not forget the stunning results from the Lyon Diet Heart Trial (de Lorgeril), which compared the effects of eating a Mediterranean-style diet to the standard prudent heart diet recommended by the American Heart Association. The results were so striking, that the study was halted mid-way by an ethics committee (It was supposed to be a 5-year study). Remarkably, there was a complete prevention of cardiac sudden death. Yet the control group, which followed the classic heart-health-diet had no such benefit.

The results of the 4-year follow-up of the Lyon Diet Heart Study were even more remarkable--an unprecedented lower death rate from all causes, especially cancer. This was an unexpected finding. The impact of this diet was also reflected in the blood phospholipids, with a lower ratio of omega-6 to omega-3 fats. The classic cardiac diet does not distinguish between the types of polyunsaturated fat, which is mostly omega-6 fat, and failed to improve the overall prognosis. But the Lyon Diet limits the amount of dietary omega-6 fats to no more than 7 grams per day, because it reflects one of the features of the classic Mediterranean diet. To put this into perspective, the typical American consumes twice this amount of omega-6 fat.

Statins Reduce Omega-6 Fats
While statins are well known for lowering cholesterol, they also by blunt the effects of excessive omega-6 fats, which are at the root of inflammation. For example, statins prevents the:

• Release of arachidonic acid from the LDL-cholesterol (Kim). Arachidonic acid is the potent omega-6 fat, which increases blood clots, arrhythmias and stiffens arteries.

• Formation of isoprenoids, another particularly potent group of inflammatory compounds, which are derived from Arachidonic acid (Lands).

While this might sound like I’m making the case for statins, to the contrary—it’s another reason to eat a Mediterranean diet, which is low in omega-6 fat and high in omega-3 fats.

When you lower omega-6 fats, you lower the fuel for inflammation. The higher dietary DHA and EPA (from fish) displaces arachidonic acid from the cell membranes, reducing inflammation further. Let’s also not forget the recent trial where fish oil out-performed statins in patients with chronic heart failure.

We also need to be mindful of possible side-effects of long-term use of statins, including muscle weakness, fatigue and deterioration. There is also a possible increase in breast cancer (Okuyama), although larger studies are needed validate this risk. The first line of defense against chronic diseases begins with a fork and a knife at the kitchen table, not reaching for pills from the medicine cabinet.

Links to Sources:

de Lorgeril M et al.
Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction : Final Report of the Lyon Diet Heart Study. Circulation 1999;99:779-785 (Free full text)

Fargnoli,JL et al. Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study. Am J Clin Nutr 2008 88: 1213-1224

Jenkins David J. A. et al.
Effects of a Dietary Portfolio of Cholesterol-Lowering Foods vs Lovastatin on Serum Lipids and C-Reactive Protein. JAMA. 2003;290(4):502-510 (Free Full Text).

JUPITER Study Group. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein N Engl J Med 2008 0: NEJMoa0807646. (Free Full Text).

Kim JY et al.
Lipoprotein-associated phospholipase A2 activity is associated with coronary artery disease and markers of oxidative stress: a case-control study. Am J Clin Nutr 2008 88: 630-637.

Lands, B
A critique of paradoxes in current advice on dietary lipids.
Progress in Lipid Research Volume 47, Issue 2, March 2008, Pages 77-106.

Okuyama H et al.
Pleiotropic effects of statins in the prevention of coronary heart disease-potential side effects.
World Rev Nutr Diet. 2007;96:55-66.

Another Bipolar Omega-6 Fat Connection

2008-11-08T19:25:00Z

Bottomline: An antidepressant medication known to trigger mania in bipolar patients is found to increase arachidonic acid metabolism in the brain, which has been linked to mania. Mol Psychiatry. 2008 Nov 4. [Epub ahead of print]

Background: Many antidepressants, particularly tricyclic antidepressants and serotonin selective reuptake inhibitors (SSRI’s), are known to induce episodes of mania or increase cycle frequency or symptom intensity in bipolar patients. Since mania mood stabilizers have been shown to decrease the arachidonic acid cascade, the NIH research team theorized that mania-triggering antidepressants might induce the mood switch via up regulating omega-6 metabolism in the brain.

Summary: Researchers compared the impact of administering imipramine versus bupropion on biomarkers of arachidonic acid metabolism in the brain, because imipramine but not bupropion, increases mania switching in bipolar patients. As predicted, imipramine caused an increase of arachidonic metabolism and biomarkers, including an increase of the enzyme (phospholipase-A2 or phospho-cPLA2), which is a key enzyme that releases arachidonic acid from the cell membrane, as shown in the figure below:

Study Quote: "The results of this study taken with published data on fluoxetine treatment, suggest that antidepressant
agents that increase switching of bipolar depressed patients to a manic state do so by increasing arachidonic acid metabolism in the brain."

Comment: This study adds to a growing body of evidence implicating excess arachidonic acid in the brain as part of the pathology in neuropsychiatric disorders, including Alzheimer's disease. For example, many of the mania medications (lithium, valproate and carbamazepine) work by lowering arachidonic acid in the brain (Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):239-46); and valproate was shown to heal brain cells and improve memory in an animal model of Alzheimer's disease (See Bipolar Drug Improves Alzheimer's Disease Symptoms).

Recently, arachidonic acid gone awry, was demonstrated in the first human brain imaging study in patients with Alzheimer's disease (See Brain Image Study Shows Increased Arachidonic Acid in Alzheimer's Patients ). And
higher levels of this omega-6 fat are associated with increased severity of symptoms in bipolar patients (See Arachidonic Acid-The Omega-6 Fat Connection to Bipolar Mood Disorder ).

Link to Study:

Lee HJ, Rao JS, Chang L, Rapoport SI, Kim HW.
Chronic imipramine but not bupropion increases arachidonic acid signaling in rat
brain: is this related to 'switching' in bipolar disorder? Mol Psychiatry. 2008 Nov 4. [Epub ahead of print]

The Mediterranean Diet is Low in Omega-6 Fat, Say Lyon Diet Heart Study Scientists

2008-11-04T19:03:00Z

Bottomline:A must-read paper, by the scientists that made "Mediterranean Diet" a household name, because of striking health benefits from their Lyon Diet Heart Study; describes the key components and common mis-characterizations of the Mediterranean diet paradigm. Curr Atheroscler Rep. 2008 Dec;10(6):518-22.

Summary: The Mediterranean diet paradigm is more than using olive oil. In contradiction with many experts, the Mediterranean diet traditionally consists of:

Dairy products, usually in the form of fermented products.

Low in omega-6 fats

Meats are raised on feeds/grasses containing the plant omega-3 fatty acid, alpha-linolenic acid (ALA)

Other characteristics include: seasonal fruits and vegetables, various nuts, whole grains, fatty fish and wine drinking during meals.

There is a thought-provoking discussion on the merits of moderate alcohol consumption versus intense cholesterol lowering on mortality. Ultimately, the scientists urge physicians to consider the feeling of “joie de vivre” when prescribing lifestyle changes for their patients.

Quote: "...the epidemiologists does not capture one major lipid characteristic of the Mediterranean diet, which is actually low in omega-6 and rich in omega-3 fatty acids. The omega-6/omega-3 ratio has been proposed as a major component of a healthy diet."

Link to Paper:
de Lorgeril M and Salen P.
The mediterranean diet: rationale and evidence for its benefit.Curr Atheroscler Rep. 2008 Dec;10(6):518-22.

Asthma Triggering Compounds from Omega-6 Fat Create Clogged Arteries

2008-10-31T16:14:00Z

Bottomline: Excellent review paper, which describes how the potent inflammatory compounds, which trigger asthma, also damage arteries, via the leukotrienes generated from the omega-6 fat, arachidonic acid. Cardiovasc Drugs Ther. 2008 Oct 24. [Epub ahead of print]

Summary: This review paper describes the accumulating body of evidence, demonstrating how leukotrienes, the powerful group of eicosanoids, infamous for damaging lungs and triggering asthma, are also involved in heart disease. The key stages of arterial damage are described, beginning with irritation of the blood vessels linings, resulting in plaque accumulation and ultimately the potentially deadly rupture of the plaque (as depicted above).

Fascinating pieces of evidence link the leukotriene-inflammation connection to: sleep apnea, periodontal disease, and chronic obstructive pulmonary disease (COPD); conditions all of which are associated with increased risk for heart disease. Experimental evidence shows that treatment with asthma drugs (leukotriene inhibitors or modifiers) reduces atherosclerosis, summarized in the diagram below:

Comment: A study on patients with a genetic profile causing increased leukotriene formation, had increased atherosclerosis if that ate a high omega-6 fat diet. (For more details see Heart Disease and Clogged Arteries--Increased Risk with Dietary Omega-6 Fat). A similar effect was recently demonstrated in breast cancer patients--those with a genetic disposition of generating leukotrienes and eating a high omega-6 fat diet, resulted in increased disease incidence. (For more details see Another New Breast Cancer Study: Omega-6 Fat Increases Risk Two-fold in Large U.S. Study

Credits and Link to Study:
Figures and diagrams are from the paper cited below (under Creative Commons Attribution Noncommercial License)

Bäck M.
Leukotriene Signaling in Atherosclerosis and Ischemia.
Cardiovasc Drugs Ther. 2008 Oct 24. [Epub ahead of print]

Bipolar Drug Improves Alzheimer's Disease Symptoms

2008-10-29T23:12:00Z

Bottomline: Valproic acid reduced brain lesions, healed brain cells and improved memory in an animal model of Alzheimer's disease. J Exp Med. 2008 Oct 27. [Epub ahead of print].

Background: There has been no effective method for the treatment or prevention of Alzheimer's disease. Previous research suggests that valproic acid, a drug used in the treatment of epilepsy and bipolar disorder, might reduce amyloid beta-protein, the central component of neural plaques and a hallmark of Alzheimer's disease.

Summary: Researchers examined the effects of valproic acid on Alzheimer's pathology in the brain and identified its underlying mechanism. Valproic acid reduced the neuro plaque formation, improved memory deficits and prompted damaged nerves to start repairing themselves in transgenic mice.

Study Quote: "Our data suggest that VPA (valproic acid) is effective for antiamyloid therapy in the prevention and treatment of AD (Alzheimer's Disease)"

Comment: Valproic acid is the medication used for treating mania in bipolar disorder and it works by limiting the arachidonic acid cascade. (See Arachidonic Acid-The Omega-6 Fat Connection to Bipolar Mood Disorder) Interestingly, recent studies have associated increased arachidonic acid with Alzheimer's disease. (See Brain Image Study Shows Increased Arachidonic Acid in Alzheimer's Patients with Arachidonic Acid: The Omega-6 Fat Linked to Alzheimer's Disease)

Link to Study:
Qing H. et al. Valproic acid inhibits A{beta} production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. J Exp Med. 2008 Oct 27. [Epub ahead of print].

Brain Image Study Shows Increased Arachidonic Acid in Alzheimer's Patients

2008-10-22T23:30:00Z

Bottomline: First human study demonstrates increased arachidonic acid levels in the brains of Alzheimer's patients, indicative of inflammation. Journal of Nuclear Medicine (Sept 2008) Vol. 49 No. 9 1414-1421.

Background: Previous studies demonstrating inflammation compounds in the brains of patients with Alzheimer's disease, together with animal imaging studies showing neuroinflammation with elevated arachidonic acid, led researchers to believe that this omega-6 fatty acid is likely elevatedin the brains of humans with this disorder.

Summary: Researchers developed a method to view neuroinflammation in brain in 8 patients with Alzheimer's disease and compared them to age-matched controls. Arachidonic acid was elevated in widespread cortical areas ofthe brain in mildly to moderately (1 severely) demented but otherwise healthypatients with Azheimer's disease, compared with age-matched controls. Notably, arachidonic acid was particularly elevated in brain regions reportedto have high densities of senile (neuritic) plaques as shown:

Theseresults indicate that elevated arachidonic acid is associated with Azheimer's disease, which is consistent with previous studies showing upregulated markers ofbrain arachidonic acid metabolism in a rat model of neuroinflammation andon the presence of neuroinflammation in Alzheimer's disease.

Comment: The increase of the arachidonic acid cascade and ensuing inflammation has been implicated in other disorders (See Arachidonic Acid-The Omega-6 Fat Connection to Bipolar Mood Disorder and Medications that Block Effects of Omega-6 Fat and Arachidonic Acid: The Omega-6 Fat Linked to Alzheimer's Disease )

Link to Study:
Esposito G. et al. Imaging Neuroinflammation in Alzheimer's Disease with Radiolabeled Arachidonic Acid and PET. Journal of Nuclear Medicine (Sept 2008) Vol. 49 No. 9 1414-1421.

Arachidonic Acid: The Omega-6 Fat Linked to Alzheimer's Disease

2008-10-21T02:32:00Z

Bottomline: Excess arachidonic acid wreaked havoc on brain cells in an animal model of Alzheimer's disease, but when omega-6 fat was lowered the neurons returned to normal function. Nature Neuroscience, published advance online 19 Oct 2008

Background: Fatty acids are rapidly taken up by the brain and incorporated into phospholipids, a class of fats that form the membrane or barrier that shields the content of cells from the external environment.

Summary: Scientists used a large scale profiling approach (“lipidomics”) to compare many different fatty acids in the brains of normal mice with those in a mouse model of Alzheimer's disease that develops memory deficits and many pathological alterations seen in the human condition. Arachidonic acid caused a dose-dependent decrease in neuronal viability.

Lead Scientist Quote: “The most striking change we discovered in the Alzheimer mice was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer's disease,” says Rene Sanchez-Mejia, M.D.

Comment: This builds on a growing body of research linking arachidonic acid with Alzheimer's disease. A 1997 study comparing cognition scores over a three-year period in two groups of men , aged 69 to 89 years , found that those who ate a diet high in omega-6 fats experienced more cognitive decline. It's interesting to note that arachidonic acid has been implicated in bipolar disorder, (See Arachidonic Acid-The Omega-6 Fat Connection to Bipolar Mood Disorder).

Link to Free Full Text Studies
Rene Sanchez-Mejia et al.
Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nature Neuroscience, published advance online 19 Oct 2008 info:doi/10.1038/nn.2213

S. Kalmijn et al.
Polyunsaturated Fatty Acids, Antioxidants, and Cognitive Function in Very Old Men. Am. J. Epidemiol. 1997 145: 33-41.

Another New Breast Cancer Study: Omega-6 Fat Increases Risk Two-fold in Large U.S. Study

2008-10-11T06:31:00Z

Bottomline: Eating high levels of omega-6 fat (linoleic acid) increases the risk of developing breast cancer nearly 2-fold in genetically susceptible women. Last month Swedish researchers found a similar risk. Linoleic acid is the most common polyunsaturated fat in the American diet.

Cancer Epidemiol Biomarkers Prev October 1, 2008(17): 2748-2754

Background: Omega-6 fatty acids have a strong promoting effect on breast cancer development in animal studies. The omega-6 fatty acids exert their cancer-promoting effects, when they are turned into inflammatory compounds by enzymes commonly found in the body, COX and LOX.

The LOX enzyme converts the potent omega-6 fat, arachidonic acid, into leukotrienes, which are inflammatory mediators in diseases such as asthma, cardiovascular diseases, and have been implicated in several types of cancers in different tissues and organs (including lung, colon, kidney, bladder and esophagus). Therefore, researchers explored the association of dietary omega-6 fat and the role of genetics related to the LOX enzyme and breast cancer.

Summary: In a case-control study on nearly 1700 women, researchers found that women with a genetic aberration effecting the LOX enzyme, combined with eating a high level of linoleic acid (>17.4 grams/day), had a significant increase in breast cancer risk, nearly 2-fold. Yet, when women with the same genetic profile ate a lower linoleic acid diet, the genotype had no influence on breast cancer risk. Notably, an unrelated study on the LOX gene, found an increased risk of atherosclerosis with eating a high omega-6 fat diet. (See Clogged Arteries--Increased Risk with Dietary Omega-6 Fat). This study demonstrates that a diet-gene interaction increases the risk of developing breast cancer, which may explain why previous human studies have been inconsistent. This is the first study to consider the impact of genetics and dietary omega-6 fat with breast cancer incidence.

Study Quote: “…our results suggest a role of the omega-6 polyunsaturated fatty acid pathway in breast cancer etiology.”

Comment: This study adds to the growing evidence of excessive omega-6 fat increasing the risk of breast cancer. Just last month Swedish researchers found a similar risk (See Omega-6 Fat May Promote Breast Cancer Development). Americans eat an average of 13 grams of linoleic acid a day, which is close to the high intake associated with breast cancer (>17.4 grams/day). Yet when genetically susceptible women ate a lower omega-6 fat diet, there was no increase in cancer risk, which may indicate that the “cancer-gene-machine” did not get switched on. This appears to be a modifiable risk factor. It may also be the reason that previous studies show an association with diets low in omega-6 fat with a reduction of all-cause mortality, which includes cancer (See What Everyone Ought to Know About the Mediterranean Diet. The highest contributors of linoleic acid in the American diet are soybean oil, corn oil and cottonseed oil. (See Foods High in Omega-6 Fat for more diet info).

Link to Study:
Wang J et al. 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein Gene Polymorphisms, Dietary Linoleic Acid, and Risk for Breast Cancer. Cancer Epidemiol Biomarkers Prev October 1, 2008(17): 2748-2754

Seed Newsvine

Inflammation 911 Podcast: The Role of Omega-6 Fats

2008-10-08T05:23:00Z

Listen to this podcast: Inflammation911.com interviews Evelyn Tribole, MS, RD, on the role of omega-6 and omega-3 fats in inflammation.

Source:
Inflammation911.com

Cystic Fibrosis:The Omega-6 Inflammation Connection

2008-10-08T00:17:49Z

Bottomline: Study demonstrates an increased conversion of the omega-6 fat, linoleic acid to arachidonic acid a potent omega-6 fat in cystic fibrosis cells, which may be what drives chronic inflammation. Adding DHA reversed the problem.

Journal of Lipid Research, Vol. 49, 1946-1954, September 2008

Summary: Decreased levels of linoleic acid and DHA are associated with cystic fibrosis patients. Researchers sought to determine the mechanism for this aberration and also looked at the impact of adding DHA to cultured airway cells resembling cystic fibrosis. They found that the airway cells draw on the linoleic acid to make more arachidonic acid, the potent omega-6 fat, which makes several types of inflammatory eicosanoids. Notably, this defect was corrected by adding DHA.

The researchers concluded that DHA is a potential candidate to dampen the chronic inflammatory response in cystic fibrosis patients as it down-regulates the production of arachidonic acid-derived inflammatory eicosanoids.

Quote: “Aggressive supplementation with linoleic acid may…lead to an increased inflammatory response as a result of its extensive metabolism to arachidonate and inflammatory eicosanoids.”

Comment: It would be interesting to conduct an intervention study similar on cystic fibrosis patients, in which they all would be supplemented with DHA, and then either put on a low-omega-6 fat diet or a classic western diet (which is high in omega-6 fat).

Link to Study:
Al-turkmani MR et al. A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA. Journal of Lipid Research, Vol. 49, 1946-1954, September 2008.

Abbreviations & Notes:

Arachidonic acid/arachidonate is the potent omega-6 fat, found in animal foods

DHA is a potent omega-3 fat, found in fish and fish oil

Linoleic acid is the omega-6 fat found in vegetable oils such as: soybean oil, cottonseed oil and corn oil

What’s the Big Deal with Tilapia? Arachidonic Acid—the Potent Omega-6 Fat

2008-10-04T00:08:00Z

Bottomline: Important study shows that modern farming practices, in this case with farmed fish, especially tilapia worsen it’s omega-6 fat and omega-3 fat profile, by increasing arachidonic acid, the most potent omega-6 fat. J Am Diet. Assoc July 2008 (108):1178-1185.

Summary: Fatty acid composition of 30 samples of fish was evaluated, with particular scrutiny on the four most commonly consumed farmed fish, Atlantic salmon, trout, tilapia, and catfish. Trout and Atlantic salmon contained relatively high amounts of EPA and DHA with low omega-6:omega-3 fat ratios. In contrast, tilapia (the fastest growing and most widely farmed fish) and catfish had much lower concentrations of omega-3 fats, with very high ratios of arachidonic acid to omega-3 fats.

Study Quote:"...farmed tilapia and catfish have low levels n-3 fatty acids along with levels of arachidonic acid so high they can be considered detrimental"

Commentary: Clearly, not all fish are created equal, especially when it comes to aqua-farming. The fat content and fatty acid profile of fish is determined by the diet fed to the fish (just like humans!) A particularly important issue here is the type of omega-6 fat, arachidonic acid, that is increased with farmed tilapia.

Arachidonic acid is the most potent and problematic of the omega-6 fats and is found in animal products, including fish. It is much more potent than the plant omega-6 fat, linoleic acid, found in vegetable oils, such as soybean oil, cottonseed oil, and corn oil. Arachidonic acid is the parent to some of the most potent inflammatory compounds, for which medicines are prescribed and/or taken over the counter. For example:

Aspirin—blocks arachidonic acid from making inflammatory eicosanoids, which cause pain, fever, swelling and cramping. Also, the nonsteroidal anti-inflammatory medicines (NSAIDs), such as naproxen and ibuprofen help block the effects of arachidonic acid. (Cleland et al)

COX-2 inhibitors (such as Vioxx and Celebrex), block the COX-2 enzyme, which turn arachidonic acid into the compounds responsible for pain, inflammation and swelling. (Cleland et al)

Singulair (montelukast) is leukotriene inhibitor that prevents arachidonic acid from making the powerful asthma-triggering compound.

Mood-Mania Stabilizers (lithium, valproate and carbamazepine), work by slowing down the effects of arachidonic acid in the brain. (Lee et al).

Statins--prevent arachidonic acid release from the LDL-cholesterol. Arachidonic acid increases blood clots, arrhythmias and stiffening of the arteries. (Kim et al).

Links to Sources:
Cleland et al.
Fish oil: what the prescriber needs to know.Arthritis Research & Therapy 2006,(free full text) 8:202doi:10.1186/ar1876

Kim JY et al. Lipoprotein-associated phospholipase A2 activity is associated with coronary artery disease and markers of oxidative stress: a case-control study. Am J Clin Nutr 2008 88: 630-637.

Lee et al.Antimanic therapies target brain arachidonic acid signaling: Lessons learned about the regulation of brain fatty acid metabolism.Prostaglandins, Leukotrienes and Essential Fatty Acids (77) Nov-Dec 2007:239-246.

Weaver KL et al. The Content of Favorable and Unfavorable Polyunsaturated Fatty Acids Found in Commonly Eaten Fish.
Journal of the American Dietetic Association July 2008 (Vol. 108, Issue 7, Pages 1178-1185)ournal of the American Dietetic Association July 2008 (Vol. 108, Issue 7, Pages 1178-1185)

Permalink: omega-6-omega-3-balance.omegaoptimize.com/2008/09/23/whats-the-big-deal-with-tilapia--arachidonic-acidthe-potent-omega6-fat.aspx

Science Reviews of Omega-6 and Omega-3 Fats on Health (Free Full Text)

2008-09-30T20:59:00Z

This is a news feed of scientific reviews (free) on the health impact of omega-6 and omega-3 fats for various conditions. Compiled by Evelyn Tribole, MS, RD using the U.S. National Library of Medicine. Updated regularly.

Arteries Damaged by Omega-6 Fat, Linoleic Acid

2008-09-29T14:44:00Z

Bottomline: Linoleic acid, the polyunsaturated fat found commonly in vegetable oils, may injure the arteries by turning on a destructive gene that triggers clogged arteries.Diabetes .2005.May;54(5):1506-13.

Summary: Earlier research (Blankenhorn, Toborek) has shown thatlinoleic acid can selectively trigger a pro-inflammatory environment in blood vessels and is associated with theappearance of new atherosclerotic lesions in coronary arteries. This study shows a new mechanism by which linoleic acid may damage arteries--by turning on the gene that increases the uptake of a potent oxidated-LDL, which is more destructive to blood vessels than regular LDL.

Study Quote: "Of all thefatty acids, linoleic acid appears to be the one with the most profoundand deleterious effects on endothelial barrier function"

Comment:This study adds to a growing evidence that links the omega-6 fatty acid, linoleic acid, to heart disease (see Linoleic Acid Hurts Heart--Cardiac Inflammation, Eating Omega-6 Fat Hurts the Heart—Framingham Heart Study, Clogged Arteries--Increased Risk with Dietary Omega-6 Fat). Ironically, linoleic acid is a polyunsaturated fat that has been widely promoted as "heart healthy" and is commonly found in margarine, mayonnaise, salad dressings, fast foods and processed foods.

Links to Studies:
Blankenhorn D et al.
The influence of diet on the appearance of new lesions in human coronary arteries JAMA 1990 263: 1646-1652. (Abstract)

Fritz Maingrette and Geneviève Renier.
Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells Diabetes. 2005 (May) 54:1506-1513 (Free Full Text).

Toborek M et al.
Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells Am J Clin Nutr 2002 75: 119-125(Full Text)Am J Clin Nutr 2002 75: 119-125(Full Text)

What Everyone Ought to Know About the Mediterranean Diet

2008-09-29T01:49:00Z

Bottomline: The classic Mediterranean diet is low in omega-6 fats.

Summary Researchers analyzed existing Mediterraneandiet studies, which involved more than 1.5 million healthy people. While there was not a standard definition of what constitutes a Mediterraneandiet--this overall pattern of eating was significantly associated with a reduced risk of death from all causes and a reduced risk of death from heart disease and cancer. The incidence of cancer, Parkinson’s disease and Alzheimer’sdisease was also significantly reduced.

BMJ 2008;337:a1344.

Study Quote: "Adiet rich in fruits, vegetables, legumes, and cereals, witholive oil as the only source of fat, moderate consumption ofred wine especially during meals, and low consumption of redmeat has been shown to be beneficial..."

Commentary:One hallmark of the Mediterranean diet is that it is low in omega-6 fat, a fact that is often overlooked, (dare I say neglected) in spite of the studies indicating its health significance! Among vegetable oils, olive oil is one of the lowest in omega-6 fat, providing 1.3 grams of linoleic acid (the plant source of omega-6 fat). Olive oil is predominantly oleic acid, an omega-9 fatty acid).

Examples:

The Lyon Diet Heart Study-which popularized the health benefits of eating a Mediterranean diet was designed and implemented as a low dietary omega-6 fat of 7 grams/day; because the researchers determined that it was one of the key features of following a Mediterranean diet ( de Lorgeril et al.) That study was published with an accompanying editorial by A. Leaf, who highlighted the importance of the low dietary omega-6 factor for heart health.

The Greek Mediterranean diet, as exemplified by the diet of Crete, is associated with the longest life expectancy and lowest rate of cardiovascular disease. It is a low omega-6 fat. And this is the Mediterranean diet, which the Lyon Diet Heart was patterned.(Simopoulos AP )

The Chianti Study–Researchers evaluated the population of two small towns in Tuscany, Italy for the effect of dietary fat and inflammation. Notably, the people in this Mediterranean region eat a low omega-6 fat diet, with an average intake of 7 grams of polyunsaturated fats (PUFA) per day.(Ferrucci L et al.) This diet was associated with lowerlevels of proinflammatory biomarkers (IL-6, IL-1ra, TNF, C-reactiveprotein) and higher levels of anti-inflammatory biomarkers (solubleIL-6r, IL-10, TGFß).

Considering that many westernized countries eat very high levels of omega-6 fats, (including eating fats that didn't exist 100 years ago, like cottonseed oil and margarine); it might be helpful to define what is not a Mediterranean diet (it is not high in omega-6 fats). And yet, these are the very fats (polyunsaturated fats) that have been touted for years by the American Heart Association, because they are considered heart healthy. Currently, the average American eats twice the maximum international recommendations of no more than 6.7 grams of omega-6 fat/day.

Link to Studies:
de Lorgeril M et al.
Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction : Final Report of the Lyon Diet Heart Study Circulation1999;99:779-785 (Free full text)

Ferrucci L et al. Relationship of Plasma Polyunsaturated Fatty Acids to Circulating Inflammatory Markers J. Clin. Endocrinol. Metab. 2006 91: 439-446; 2005-1303 (Free full text)

Leaf A.
Dietary Prevention of Coronary Heart Disease : The Lyon Diet Heart Study Circulation 1999;99:733-735 (Free full text)

Simopoulos AP.
What Is So Special about the Diet of Greece? The Scientific Evidence World Rev Nutr Diet. Basel, Karger, 2005, 95:80-92 .(Abstract w/free preview)

Sofi F et al.
Adherence to Mediterranean diet and health status: meta-analysis BMJ 2008 337: a1344-a1344 (Free full text)

Foods High in Omega-6 Fat

2008-09-28T21:13:00Z

Omega-6 fatty acids are the most common polyunsaturated fat consumed in the US diet. The top three sources of omega-6 fat in the American diet are soybean oil, cottonseed oil and corn oil. You'll find them as key ingredients in margarine, mayonnaise, salad dressings, snack foods, processed foods and fast foods. They are also high in so-called health foods such as granola and veggie burgers.

There are two key dietary omega-6 fatty acids, one found in plants, called linoleic acid and the other is found in animal foods, arachidonic acid.

The omega-6 fat listed in the table below is from linoleic acid. Notice how some of the perceived healthy foods are high in omega-6 fat, exceeding the ceiling recommendation of 6.7 grams maximum/day (see International Guidelines link for more details).

Foods High in Omega-6 Fat*	Omega-6 fat (grams)	% Maximum (6.7 grams/day)
Oils (per 1 Tablespoon)
Safflower oil	10.1	151%
Grapeseed oil	9.5	142%
Vegetable oil	7.9	118%
Wheat germ oil	7.5	112%
Corn oil	7.3	109%
Walnut oil	7.2	107%
Cottonseed oil	7.0	104%
Soybean oil	6.9	103%
Sunflower oil	5.4	81%
Spreads (per 1 Tablespoon)
Mayonnaise, regular soybean oil	5.2	78%
Margarine, tub regular	3.8	57%
Promise Buttery spread, 60% vegetable oil	3.4	51%
Processed Foods (per serving)
Burger King Chicken Whopper (1)	11.5	172%
McDonald's Filet O Fish (1)	6.3	94%
Pizza Hut cheese pizza (2 sl medium pan-style)	4.9	73%
Granola bar (1 bar)	2.9	43%
Frankfurter, vegetarian (1)	2.4	36%
Frankfurter, pork (1)	1.5	22%
Veggie burger (1 patty)	1.4	21%
Smart Balance light Popcorn (1 serving is 4 cups)	1.3	19%
*Adapted from Ultimate Omega-3 Diet

Medications that Block Effects of Omega-6 Fat

2008-09-26T16:40:00Z

Bottomline: Arachidonic acid , the potent omega-6 fat, creates health-harming inflammatory chemicals in the body. Many anti-inflammatory medications such as aspirin, Celebrex and Singulair work by blunting the effects of omega-6 fat.

Many of the health benefits derived from omega-3 fats in fish oil (EPA and DHA) are from their ability to block the harmful effects of arachidonic acid. Arachidonic acid is the most problematic of the omega-6 fats and is found in animal products. The plant omega-6 fat, linoleic acid, commonly found in vegetable oils (especially soybean oil, cottonseed oil, and corn oil), easily gets made into arachidonic acid by the body.

When you eat a diet high in omega-6 fat and low in omega-3 fat, it paves the way to make more arachidonic acid. The arachidonic acid gets holstered into heart cells, brain cells, red blood cells, lung cells and fat cells, increasing inflammation throughout the body. For example, these conditions are triggered by excess arachidonic acid: asthma, arthritis, headaches, cramps, pain, swelling and fever. The medications used to treat these conditions, work by stopping this potent omega-6 fat.

Hare are just a few example:

Aspirin—blocks arachidonic acid from making inflammatory eicosanoids, which cause pain, fever, swelling and cramping. Also, the nonsteroidal anti-inflammatory medicines (NSAIDs), such as naproxen and ibuprofen help block the effects of arachidonic acid. (Cleland et al)

COX-2 inhibitors (such as Vioxx and Celebrex), block the COX-2 enzyme, which turn arachidonic acid into the compounds responsible for pain, inflammation and swelling. (Cleland et al)

LOX-inhibitors (such as zileuton or Zyflo), block the LOX enzyme, which turns arachidonic acid into powerful leukotriene compounds, which are responsible for asthma, allergies and possibly atherosclerosis (clogged arteries). Leukotriene modifiers are available in the United States only by prescription for asthma and allergic rhinitis. Other leukotriene modifiers include zafirlukast (Accolate), Singulair (montelukast) and zileuton (Zyflo). (Scow DT et al.)

Mood-Mania Stabilizers (lithium, valproate and carbamazepine), work by slowing down the effects of arachidonic acid in the brain. (Lee et al).

Statins--prevent arachidonic acid release from the LDL-cholesterol. Arachidonic acid increases blood clots, arrhythmias and stiffening of the arteries. (Kim et al).

Comment: Many scientists believe that excess omega-6 fat in the diet is responsible for many of the chronic diseases in industrialized cultures including heart disease, cancer, mood disorder, allergies, asthma and arthritis. They call this problem "Excessive Linoleic Acid Syndrome" or Omega-6 Fat Syndrome. (Okuyama 2007) Notably, when arthritis sufferers lowered the omega-6 fat in their diet, in conjunction with taking fish oil--they cut their prescription medication use by 50%! Yet, those who only took fish oil without lowerin their dietary omega-6 fat did not have these same benefits. (Cleland et al).

Links to Sources:
Cleland et al.
Fish oil: what the prescriber needs to know.Arthritis Research & Therapy 2006,(free full text) 8:202doi:10.1186/ar1876

Kim JY et al.
Lipoprotein-associated phospholipase A2 activity is associated with coronary artery disease and markers of oxidative stress: a case-control study. Am J Clin Nutr 2008 88: 630-637.

Okuyama, H. Omega-3 Fatty Acids Effectively Prevent Coronary Heart Disease and Other Late-Onset Diseases – The Excessive Linoleic Acid Syndrome. World Rev Nutr Diet. Basel, Karger, 2007, vol 96, pp 83-103.

Scow DT et al.
Leukotriene inhibitors in the treatment of allergy and asthma. Am Fam Physician 2007 Jan(Free full text)75(1):65-70.

Fish Oil Substituted for Soybean Oil Heals Liver Complication

2008-09-23T16:45:00Z

Bottomline: Critically ill children depending on life-sustaining intravenous feeding, improved when fish-oil replaced the conventional soybean oil emulsion. Pediatrics 2008 121 (March): e678-e686.

Background: In the USA, the standard fat emulsion used to feed critically ill patients is soybean oil, which is high in omega-6 fatty acids. Liver disease is a complication that may develop from using life-sustaining nutrition infusion (parenteral nutrition), especially in children, where it can be fatal. Some researchers believe that the standard use of soybean oil may be the cause of this complication because of its proinflammatory omega-6 fats.

Summary: Parenteral nutrition-dependent children, who developed, cholestasis, a liver condition indicated by a serum bilirubin level of >2 mg/dL), hadtheir conventional soy-oil emulsions discontinued and replacedby a fish-oil–based emulsion. The fish-oil group experienced reversal of theircholestasis faster than subjects in the soybean-oil group. By 9 weeks the fish oil group reversed the cholestasis, compared to44 weeks in the comparison cohort group. The amount of time that it takes to heal the liver is significant significant, because once liver disease has developed, the death rate can be as high as 100% in those childrenunable to be weaned off parenteral nutrition within a year of diagnosis. It is not clear if these benefits are because of the absence of soybean oilor because of the presence of fish oil.
Study Quote: "Ourresults suggest that fish-oil–based emulsions may reversePNALD when used in place of standard soybean emulsions."

Comment: This study adds to a growing body of research that the standard use of soybean oil for patients who are unable to eat or are unable to use their GI tract, might hamper patient recovery because it contains a high level of omega-6 fat (Koch & Heller, 2005 and Mayer & Seeger, 2008).

Links:
Gura, K et al.
Safety and Efficacy of a Fish-Oil-Based Fat Emulsion in the Treatment of Parenteral Nutrition-Associated Liver Disease.Pediatrics 2008 121: e678-e686 (free full text).

T . Koch , A . Heller
Benefits of omega-3 fatty acids in parenteral nutrition.
Clinical Nutrition Supplements ,Volume 1 ,Issue 3 ,Pages 17 - 24

Mayer K, Seeger W.
Fish oil in critical illness.
Curr Opin Clin Nutr Metab Care. 2008 Mar;11(2):121-7.

Linoleic Acid Hurts Heart--Cardiac Inflammation

2008-09-15T02:59:00Z

Bottomline: An important study showing that high linoleic acid (omega-6 fat) stresses the heart.
Am J Physiol Heart Circ Physiol 293: H2919-H2927, 2007.

Summary. This animal study provides new evidence that 1 month of feeding a diet differing in the linoleic acid-to-alpha-linolenic acid (omega-6 to omega-3 fat ratio) has a dramatic effect on the heart cells. When linoleic acid is high it caused an increase in:
     -LOX and COX enzymes, central to activating the inflammation cascade in the heart
     -Arachidonic acid, the potent omega-6 fat, in heart cells
     -Enzymes that release fatty acids tethered to the phospholipids from heart cells
Notably, the different omega-6 diets tested reflect levels eaten by humans. The study demonstrated that the potential heart health benefits of high dietary ALA and incorporation of EPA, and DHA is not achieved when the diet is rich in linoleic acid.   However, lowering the dietary omega-6 to omega-3 ratio closer to 1:1 decreases inflammatory enzymes activation and reduces lipid peroxidaton and nitrotyrosine production in the heart.

Study Quote: "Our results also clearly raise the possibility that any positive effects of ALA are only realized when the diet is also low in LA."

Comment: This is the first study to demonstrate a new way that excess dietary linoleic acid can hurt the heart---by inceasing nitrosative stress, which can damage heart tissue and DNA. There have been two other studies on humans showing that high omega-6 fat diets can cause damage to the cardiovascular system (Eating Omega-6 Fat Hurts the Heart—Framingham Heart Study and Heart Disease and Clogged Arteries--Increased Risk with Dietary Omega-6 Fat_)

Link to Abstract:
Sanjoy Ghosh, Elizabeth M. Novak, and Sheila M. Innis.
Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 {alpha}-linolenic acid ratios in normal, fat-fed pigs. Am J Physiol Heart Circ Physiol 293: H2919-H2927, 2007.

How Much Omega-6 Fat is Too Much?

2008-09-14T20:28:00Z

How much omega-6 fat is unhealthy and how much should you eat?

A. A committee of scientists from around the world gathered in Washington D.C to answer that question. They recommended a range of 4.44 to 6.67 grams of omega-6 fat (specifically, linoleic acid) per day. They stated that enough scientific evidence exists to cap the limit to a maximum of 6.67 g/day, which is the amount of omega-6 in one tablespoon of corn oil or soybean oil. Currently, the typical American eats nearly double that amount, averaging 13 grams of omega-6 fat each day.

Notably, the Lyon Diet Heart study, which popularized the health benefits of eating a Mediterranean diet, also capped the dietary omega-6 fat intake to a similar level of 7 grams per day. This study made headline news because of it's remarkable (and unprecedented) lower death rate from all causes, especially cancer. The stunning results were published in the American Heart Association's scientific journal, Circulation (de Lorgeril); accompanied by an editorial (Leaf) , which stressed that only the diet with the lower omega-6 fat and higher omega-3 fat was beneficial. Interestingly, another group of people in the Lyon Diet Heart study, were put on a classic cardiac diet, which was high in omega-6 fat and they had no such improvement. (Keep in mind the emphasis of eating a heart healthy diet is to replace saturated fats with polyunsaturated fats, which is synonymous with increasing omega-6 fat).

To lower dietary omega-6 fat, means cooking primarily with olive oil, and choosing foods that are made from olive oil, flax seed oil, canola oil or high-oleic oils. The top three contributors of omega-6 fat in the diet are soybean oil, cottonseed oil and corn oil; and foods made with these oils, especially margarines, salad dressings and mayonnaise.

Link to Full Text Sources:
Simopoulos, Artemis P., Leaf, Alexander, Salem, Norman, Jr Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids.J Am Coll Nutr 1999 18: 487-489. (free full text)

Michel de Lorgeril, Patricia Salen, Jean-Louis Martin, Isabelle Monjaud, Jacques Delaye, and Nicole Mamelle Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction : Final Report of the Lyon Diet Heart Study Circulation 99: 779-785. (free full text)
Circulation 99: 779-785. (free full text)

Alexander Leaf. Dietary Prevention of Coronary Heart Disease : The Lyon Diet Heart Study.Circulation 99: 733-735 (free full text)

Arachidonic Acid-The Omega-6 Fat Connection to Bipolar Mood Disorder

2008-09-09T02:16:00Z

Bottomline:This study adds to the growing body of evidence that arachidonic acid plays a role in bipolar disorder (BPD), and higher levels of this omega-6 fat are associated with increased severity of symptoms. Bipolar Disord. 2007 Nov;9(7):759-65.

Summary: Researchers analyzed blood levels of 10 bipolar patients, recently hospitalized for an acute manic episode. They evaluated omega-3 fats (DHA and EPA), omega-6 fat (arachidonic acid), and related metabolites, and compared these levels to those of 10 healthy volunteers. An increase in the severity of manic symptom was associated with a high ratio of arachidonic acid to EPA, which according to the researchers, could indicate that a brain imbalance of fatty acids, of omega-6 fats greater than omega-6 fats, may be a non-specific contributor to illness in either mood direction.

Study Quote: "These preliminary findings imply that optimizing the ratio of n-6 to n-3 PUFAs in the plasma, through dietary or drug interventions, may prove to be a favorable adjunct treatment for preventing or diminishing the manic phase in BPD."

Comment: Many of the mania medications (lithium, valproate and carbamazepine) work by lowering arachidonic acid in the brain. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):239-46.

Link to Free Full Text:
Sublette ME, Bosetti F, DeMar JC, Ma K, Bell JM, Fagin-Jones S, Russ MJ, Rapoport SI. Plasma free polyunsaturated fatty acid levels are associated with symptom
severity in acute mania. Bipolar Disord. 2007 Nov;9(7):759-65.

Dry Eye Syndrome (DES)- Omega-6 Fat to Omega-3 Fat Ratio Influences Risk

2008-09-08T06:41:00Z

Bottomline: This is the first study to show that a high dietary omega-6 fat to omega-3 fat ratio is associated with a higher risk of developing Dry Eye Syndrome (DES), one of the most prevalent eye problems that leads to vision difficulties while reading, using a computer and driving at night.
Am J Clin Nutr. 2005 Oct;82(4):887-93.

Summary: Researchers evaluated the diets of nearly 30,000 women, and found that a diet high in omega-3 fats decreased the risk of developing DES, which affects more than10 million Americans. Notably, eating about three-ounce of tuna, once per week was found to be particularly protective. Conversely, a high dietary omega-6 fat to omega-3 fat ratio greater than 15:1 was associated with a more than twofold greaterprevalence of DES than was seen with a low ratio.

A body of research has shown that dietary intakeof omega–3 fats and the ratio of their consumptionto that of omega–6 fats affects the overall inflammation status in the body. Notably, patientswith DES have an increased concentration of inflammation compounds in the tear fluid (including cytokines,such as interleukin 1, interleukin 6, and tumor necrosis factor.)
Researcher's Conclusion:"Giventhe biology and importance of these FAs and their opposing biologicaleffects, it seems quite likely that such an imbalance wouldbe related to a pathologic condition"
Comment: This group of women had a lower omega-6 fat ratio than the typical western diet (90% had a ratio belowcurrent USA recommendations). Therefore the researchers speculate that it's possible that imbalances of the dietary omega-6 fat to omega-3 fat ratio might have an even more profound impact on DES patients.

Link to FREE Full Text
Miljanović B et al. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women.Am J Clin Nutr. 2005 Oct;82(4):887-93.