Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Wednesday, February 4, 2009

American Heart Association OKs Linoleic Acid and Arachidonic Acid

Can the AHA be correct in promoting omega-6 PUFAs? Doesn't this conflict with the broad therapeutic action of omega-3 PUFAs, EPA/DHA, against inflammatory diseases?

The dietary shift from saturated animal fats to polyunsaturated fatty acids (PUFAs) from vegetable oils paralleled the shift from infectious diseases to inflammatory/degenerative diseases as predominant killers in the Western world. Treatments for degenerative diseases associated with aging have improved, but these diseases have become more prevalent and the age of onset has decreased. And medical costs have skyrocketed. Omega-6 vegetable oils seem to be the problem, but the American Heart Association (AHA) has recently given these PUFAs a clean bill of health.

Why the AHA Conclusions Seem Just Wrong

The rise of inflammatory/degenerative diseases follows the shift to processed foods rich in omega-6 PUFAs (corn, soy, cottonseed, safflower oils) and simple carbohydrates (grain starch, sugar, high fructose corn syrup), but the AHA presents scientific data to exonerate omega-6 PUFAs. The central problem is that the AHA’s conclusions are not based on a conceptual framework to explain cardiovascular disease. Instead, conclusions are derived from experiments in which various diets are fed to people and consequences are analyzed. With some diseases, in which there is a simpler cause and effect relationship, this approach might lead to useful answers, unfortunately, the inflammatory component central to cardiovascular disease can have multiple, alternative origins and simple experiments yield misleading conclusions.

Experimental Basis for AHA Support for Omega-6 PUFAs

  • Conversion of short PUFAs found in the diet, e.g. LA, to the long PUFAs that serve as the precursors of cellular hormones. But conversion is thought to be inefficient, so that less than 1% conversion occurs and short PUFAs have little impact on cellular long PUFA concentrations. Moreover, the brain does not perform the conversion and the high brain content of DHA is supplied on demand from DHA circulating in the blood.
  • There don’t appear to be any direct, inflammatory derivatives of LA (C-18), but after it is converted to AA (C-20), the arachidonic acid is the starting point for the conversion to most of the inflammatory and anti-inflammatory cellular hormones, e.g. prostaglandins, leukotrienes and lipoxins. Thus inflammation is initiated by AA-derived products, but resolution and return to normal physiology is also based on other AA-derived products.
  • Increases in blood plasma AA are associated with anti-inflammation, not inflammation.
  • Increases in dietary AA and/or LA result in a decrease in cardiovascular disease. Replacing dietary saturated fat with PUFA leads to a reduction of disease by 25-50%. Higher serum LA translates into less disease.
  • Increases in dietary LA result in lower serum cholesterol and LDL, but paradoxically they also lead to a narrowing of arteries.
  • The relative amounts of dietary PUFAs (USA) are LA 15grams/day, AA 0.15g/d, ALA (omega-3, C-18, linolenic acid) 1g/d, EPA/DHA <>

Statins Lower Cardiovascular Disease by Lowering Inflammation (LDL Not Important)

The JUPITER study showed that the statin Crestor was effective in lowering heart disease, because it lowered inflammation. Individuals with chronic inflammation responded to Crestor by lowering inflammation. Lowering of LDL levels, however, was not related to decreasing disease. Elevated LDL levels may reflect inflammation.

Relating the JUPITER results to the AHA conclusions suggests that LA and AA may reduce inflammation and as a consequence also reduce serum LDL.

Inflammation Is the Cellular and Tissue Response to Many Stresses

The list of pathogens that trigger inflammation is long and includes specific signals from viruses, bacteria, fungi and protozoa. Pathogen-caused damage, as well as physical trauma, cause inflammation. Disruption of cellular metabolism and energy flow by vitamin, mineral, amino acid, or fatty acid deficiencies or excesses all produce inflammation. One of the difficulties of diagnosis is the overlapping of symptoms originating from numerous sources of underlying inflammation. Herniation of vertebral disks, for example, can be triggered by physical trauma, but it also may be initiated by the intestinal inflammation of gluten-based celiac. Acne and depression are common symptoms of chronic inflammation that may result from dietary deficiencies, gum disease, gluten sensitivity, etc. All of these examples respond to anti-inflammatory diets.

It is difficult to identify the sources of inflammation in experimental studies. In cardiovascular disease, the sources of inflammation are commonly not known in individual cases and the cardiac symptoms are treated. In reality, these are actually many different diseases, all with different sources of inflammation, pigeon-holed under the same symptom, a cardiac event. The most effective long term treatment for the dispart group is general suppression of inflammation. Any specific treatment of a root cause only works on a small subset of the group and would be considered ineffective. Thus, statins are considered effective against heart disease, because they reduce inflammation that is common to the whole group. Reduction of LDL is inadvertently used as a measure of control of inflammation and has become inappropriately designated as a risk factor. Directly lowering LDL has no impact on heart disease, but it is easy to measure. Inflammation is hard to measure and finding the source of inflammation is harder still.

Omega-6 Vs. Omega-3 Is Another False Dichotomy

Just as there is no opposite to inflammation, omega-6 and omega-3 fatty acids are not in opposition. The action of aspirin is the big clue. Aspirin changes the structures of the enzymes involved in converting AA into inflammatory prostaglandins and leukotrienes, with the result that anti-inflammatory lipoxins are produced instead. Aspirin is a biochemical switch that mimics the natural transition of the cellular machinery from producing enzymes that accentuate inflammation, to enzymes and signals that are the next step in the cycle, repair and restoration of normalcy.

Omega-6 PUFAs are needed for both inflammation and restoration of normal cellular functions. Some of the enzymes produced during inflammation are needed for the reset to normalcy. The difficulty comes when inflammation is sustained, components are depleted and the cycle cannot be completed. The result then is chronic inflammation, the symptoms of metabolic syndrome and degenerative diseases.

Why Did Demonizing LA and AA Seem Right?

It seems wise not to trust medicine, dietitians and the food industry, because they have made so many lamentable mistakes making dietary suggestions that have shortened so many lives. Professional societies like the AHA also frequently give silly advice, because the advice doesn’t reflect the best information from the biomedical literature. So it makes sense to be skeptical.

In this case the AHA appears to be right, only because established views were supported by straightforward experiments. What determines if an excess of dietary LA and AA is going to be a problem with inflammation is the absolute amount of AA and EPA available on the surface of immune cells. PUFAs are attached as part of the phospholipids of the lipid rafts on the membrane surface of immune cells that have received a inflammatory signal, e.g. bacterial lipopolysaccharide. There is usually adequate AA to be converted by enzymes on the cell surface to produce further inflammatory signals. The problem comes if there is so much AA that the EPA never made it to the lipid rafts. The result would be inadequate EPA conversion to anti-inflammatory prostaglandins and failure to return to normalcy. This would be a particular weakness in the presence of a large depletion of the EPA pools during sustained inflammation and chronic inflammation would result.

Thus, the AHA promotion of omega-6 PUFAs is half right. They should have said that omega-6 fatty acids are not a problem, if there is adequate EPA/DHA and no sustained inflammation. Unfortunately, the Western diet provides inadequate EPA/DHA and deficiencies that constantly produce inflammation. Of course, those enjoying an anti-inflammatory diet and lifestyle have biochemical tolerance for the AHA’s suggestions. Others eat vegetable oils at their peril.


Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F. 2009. 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. 2009 Jan 26. [Epub ahead of print]


Nigel Kinbrum said...

Once again, you've hit the nail on the head. There's nothing wrong with omega-6 fats per se, as they are essential fats. It's the balance (with omega-3 fats) that people get wrong.

The various Associations seem rather blinkered in their outlook. The American Heart Association only looks at what's good for the heart (lots of omega-6 fat & statins) and ignores the rest of the body. The American Dermatological Association only looks at what's good for the skin (no sun) and ignores the rest of the body.

Nigel Kinbrum said...

RE Statins: If lowering LDL-c alone reduces the risk factor for CHD, how come potent cholesterol-lowerers like Squalestatins haven't made it through clinical trials? See Lapaquistat.

On paper, Lapaquistat looks ideal as it only inhibits squalene synthase, which has no effect on isoprenes which are required for the synthesis of Co-Q10 & dolichol.

I'm guessing that the adverse effects of just lowering cholesterol outweighed the benefits. HMG CoA reductase inhibitors don't just lower cholesterol, as you've pointed out.

Dr. Art Ayers said...

I agree with all of your points and extend your criticism of statins. Statins were identified by testing fungal extracts for the ability to inhibit HMG-CoA reductase. They found potent inhibitors, but ignored interactions with dozens of other enzymes/receptors. It is the other interactions (statins acting on NFkB) that are important for CHD and they act by controlling inflammation. LDL has nothing to do with it. Lowering LDL by itself does not impact CHD. Inflammation does raise LDL, so lowering inflammation lowers CHD risk and LDL.

Evelyn Tribole, MS, RD said...

I agree! Here are some more factors to consider:

What is AHA's Agenda?
The AHA made sweeping statements that are not supported by the research, while ignoring landmark studies, which don't support their views.

Here's one example. Conspicuously absent from AHA's report were the findings of the famous study, which made the Mediterranean diet a household name---the Lyon Diet Heart study.

This large intervention trial involved two groups of heart patients from France, who 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 group eating the Mediterranean diet had a striking 70% reduction in all causes of death, including cancer, compared to the group eating the "heart healthy diet".

If you interviewed, Michel de Lorgeril, the lead investigator of that famous study, he would likely disagree with AHA's advisory. Why? Because his study was specifically designed to be low in omega-6 fat, to mirror the indigenous mediterranean diet of Crete Islanders, who have a low rate of heart disease. Just last month, de Legoril 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". (Notably, the authors of AHA's advisory were mainly epidemiologists.)

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.

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.

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.

Lastly, there is a curious association with Unilever, a large global margarine manufacturer. Three of the 12 scientists declared that they received either advisory or consulting fees from this food conglomerate. Keep in mind that margarines, salad dresings and spreads are among the highest sources of omega-6 fat in westernized countries.

These are just a few examples of the problems with AHA's advisory (there are many more). I hope that for the sake of a balanced perspective and journalistic integrity, medical news media including Medscape, will investigate this issue---rather than blindly accept what the AHA proclaims--as there is alot more to this story.

Evelyn Tribole, MS, RD

ps-here is the link to the citations, with full text access:

Stephan Guyenet said...

Hi Dr. Ayers,

I don't believe the clinical trials have shown that replacing saturated fat with vegetable oil reduces CHD deaths and risk of death overall. If you look at the controlled trials, there were 12 of them that looked at total mortality and isolated the saturated fat variable. 8 showed no significant difference in total mortality, 2 showed a significant increase, 2 showed a decrease. Of the two that showed a decrease, one was the Finnish mental hospital trial, which is uninterpretable due to a poor study design. The other had significantly more heavy smokers in the control group. Of the studies that reported CHD mortality, the large majority showed no significant effect.

I think it's interesting to note that the earlier trials had a greater tendency to show that replacing saturated fat with vegetable oil is harmful. The Coronary Club trial and the Rose et al study, for example, showed a massive increase in coronary deaths when saturated fat was replaced with vegetable oil. The baseline linoleic acid intake was considerably lower back then, so those are the studies that would be expected to show the greatest effect of upping vegetable oil.

There are mechanisms for linoleic acid toxicity that I don't believe depend on arachidonic acid and its downstream products. For example, high-LA diets increase lipid peroxidation dramatically in the heart. They also deplete vitamin E. Those are probably simply due to LA's chemical instability. That's a property of LA that will remain even if you balance it with omega-3. So I think it's best to keep LA low and balanced with omega-3, rather than high and balanced.

I just found your blog, I've been enjoying it. You might enjoy mine as well.

Anonymous said...

I’m big reader of your exciting articles, but in this one there’s a big goal of confusion.
Barry Sears divulgated to the people in the early decade the eicosanoids’story:
Omega6 LA (18:2n)
Enzyme Delta-6-Desaturase
Omega6 GLA (18:3n)
Omega6 DGLA (20:3n) – Anti Inflammatory Eicosanoids
Enzyme Delta-5-Desaturase
Omega 6 AA (20:4n) – Pro Inflammatory Eicosanoids
The key is the Enzyme D5Desaturase, enhanced by Insulin.
This is why High Load LA and High Chronic Insulin Level are together damaging.
Omega 3 EPA is crucial in competing whit AA in the Essential Fatty Acids releasing phase in the Cell Membranes, but it does not produce anti-inflammatory eicosanoids.
This is the Sears Story.
Is this story right or not?
If not, it would be crucial for all of us that you explain the trouble.

Thanks for sharing you science!