Meta-analysis Reveals ï¿½Heart Healthy Omega-6 Fatï¿½ Increases Risk of Heart Disease

Ted_Hutchinson · ï¿½ #1 ï¿½ 12-03-2010, 10:48 AM

Meta-analysis Reveals “Heart Healthy Omega-6 Fat”
Increases Risk of Heart Disease By Evelyn Tribole, MS, RD

Bottom Line: The research upon which the American Heart Association based their "eat-your-omega-6-fat" advisory, is fatally flawed, according to the results of a meta-analysis study, which showed that a steady diet of omega-6 polyunsaturated fatty acids increases the risk of heart disease and death, especially for women [1]. British J Nutr. Dec 2010.

Background: ln 2009 the American Heart Association (AHA) published a health advisory touting the benefits of eating a high omega-6 polyunsaturated fatty acids (PUFA), and warned that eating less than 5% of calories from omega-6 PUFA would be hazardous to heart health. [2-3].

The conclusion of AHA's advisory were seriously questioned in part, because of their failure to:
• Distinguish the types of PUFA used in studies, which also substantially increased omega-3 fats, which are also PUFAs.
• Include relevant trials with unfavorable results.
• Exclude poorly designed studies.
Notably, these studies did not provide or differentiate the specific fatty acid content of the intervention diets. (Yet the AHA recommended to specifically increase omega-6 PUFA).
These flaws prompted a team of National Institutes of Health (NIH) scientists to re-evaluate the data, using techniques resembling a scholarly forensic investigation.
Design: Nine randomized controlled trials (the gold standard of study design), were identified, which met the criteria of having an intervention diet high in PUFA at the expense of other fat and also reported clinical outcome data.

Next came the detective work, worthy of an Agatha Cristy who-done-it. Most of the studies did not provide omega-3 fat data--it was just lumped together in the PUFA category.

In order to track down the missing fatty acid data, (many of these studies were conducted over 40 years ago), they had to dig through newspaper archives, public records, scientific proceedings from national conferences and correspond with the study investigators (or their colleagues, if deceased).

Once the fatty acid data was collected, they were segregated into two categories:
• Mixed Diet (containing both omega-6 and omega-3 polyunsaturated fatty acids.)
• Omega-6 Specific Diet

Then the data was pooled to evaluate the effect of the Omega-6 Specific Diet, compared to the effect of the Mixed Diet, on clinical outcomes. They also evaluated the potential confounding role of trans fatty acids.
Results: Here's what they found when evaluating the composition of the intervention diets.
Only three of the nine so-called PUFA studies were "pure" omega-6 intervention trials, which upped omega-6, without a concurrent rise in dietary omega-3. Combined, these three studies had 9,500 participants.
Four of the studies increased both the omega-3 PUFA (EPA and DHA) and omega-6 PUFA, which totaled over 1,700 participants. Notably, the researchers discovered that the Oslo Diet-Heart Study provided about 5 grams of EPA and DHA per day to the intervention group.
(That's equivalent to about 16 fish oil capsules).
• The control diets had a mean estimated transfatty acid content of 3% (a significant confounding factor, which unquestionably increases risk of heart disease).
Heart Disease and Death Outcomes
When the effects of the Omega-6 Specific Diet were compared to the Mixed Omega 6/omega-3 PUFA; the following health outcomes were discovered:
Omega-6 Specific Diet:
∗ Increased risk of heart disease and death, compared to the Mixed Diet intervention studies.
∗ The relative risk of cardiac death increased by 28%.
∗ Increased the risks of all relevant cardiovascular outcomes.
∗ There was only one study with women, which showed significant harm.
The Mixed Omega-6/Omega-3 Diet:
• There was 8% risk reduction of death from all causes.
• There was 22% risk reduction from heart disease death.
Conclusion: The scientists concluded, that not only is there no indication of health benefit, from increasing dietary omega-6 PUFA, but a possibility of harm. Therefore, they recommended that the public health advice to maintain or increase dietary omega-6 PUFA, should be reconsidered.
Study Quote: “The increased cardiovascular heart disease risks from omega-6 specific PUFA diets in our meta-analysis may be underestimated as omega-6 PUFA also replaced substantial quantities of trans fatty acids."
An accompanying editorial applauded the “extensive detective work” by the NIH by the NIH research team, led by Christopher Ramsden [4]

Commentary: There is more to this story.
In my next post, I'll describe what went on behind the scenes, as three NIH scientists from this study, tried to get letters to the editor published in the AHA's scientific journal, Circulation, in response to their omega-6 advisory. (I was actually a participant and witness).
Links to Sources
[1] Christopher E. Ramsden,Joseph R. Hibbeln,Sharon F. Majchrzak and John M.Davis (2010).Omega-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. British Journal Nutrition. Dec 2010; 104(11): pp 1586-1600.

[2] 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.]

[3] American Heart Asssociation News Release.
Omega-6 fatty acids: Make them part of heart-healthy eating DALLAS, Jan.
27, 2009. [Free full Text]
[4] Philip C. Calder (2010).The American Heart Association advisory on n-6 fatty acids: evidence based or biased evidence? British Journal Nutrition. Dec 2010; 104(11): pp 1575-1576.[Abstact]

Ted_Hutchinson · ï¿½ #2 ï¿½ 12-03-2010, 10:56 AM

Diet-Heart Controlled Trials: a New Literature Review

Quote:

Many controlled studies have measured the cardiovascular effects of replacing animal ("saturated") fats with seed oils (predominantly the omega-6 polyunsaturated fat linoleic acid) in humans. A number of these studies recorded heart attacks and total mortality during the following 1-8 years. Several investigators have done meta-analyses (literature reviews) to try to tease out overall conclusions from these studies.

I'm pleased to point out a new meta-analysis of these controlled trials by Dr. Christopher Ramsden and colleagues (1). This paper finally cleans up the mess that previous meta-analyses have made of the diet-heart literature. One recent paper in particular by Dr. Dariush Mozaffarian and colleagues concluded that overall, the controlled trials show that replacing animal fat with linoleic acid (LA)-rich seed oils reduces heart attack risk (2). I disagreed strongly with their conclusion because I felt their methods were faulty (3).

Dr. Ramsden and colleagues pointed out several fundamental flaws in the review paper by Dr. Mozaffarian and colleagues, as well as in the prevailing interpretation of these studies in the scientific literature in general. These overlap with the concerns that I voiced in my post (4):
Omission of unfavorable studies, including the Rose corn oil trial and the Sydney diet-heart trial.
Inclusion of weak trials with major confounding variables, such as the Finnish mental hospital trial.
Failure to distinguish between omega-6 and omega-3 fatty acids.
Failure to acknowledge that seed oils often replaced large quantities of industrial trans fats in addition to animal fat in these trials.
Dr. Ramsden and colleagues accounted for all of these factors in their analysis, which has never been done before. They chose inclusion criteria* that made sense, and stuck with them. In addition, they did an impressive amount of historical work, digging up old unpublished data from these trials to determine the exact composition of the control and experimental diets. The paper is published in the British Journal of Nutrition, an excellent journal, and overall is written in a scientific and professional manner.

What did they find?
Interventions that replaced animal and trans fat with seed oils that were rich in LA but low in omega-3 caused a non-significant trend toward increased heart attacks (13% increase) and overall mortality.
Interventions that replaced animal and trans fat with a combination of LA and omega-3 fats significantly reduced heart attacks (by 22%). The numbers for total mortality followed a similar trend.
In other words, LA-rich seed oils do not prevent heart attacks (and may actually promote them), but correcting an omega-3 deficiency and reducing industrial trans fat intake may be protective. This is similar to what I've been saying for a while now, based on my own interpretation of the same studies and others. However, Dr. Ramsden and colleagues have taken the idea to a new level by their thorough and sophisticated detective work and analysis. For example, I didn't realize that in virtually all of these controlled trials, the intervention group reduced its trans fat intake substantially in addition to reducing animal fat. From the paper:
...experimental diets replaced common ‘hard’ margarines, industrial shortenings and other sources of [trans fat] in all seven of the [controlled trials] included in the meta-analysis by Mozaffarian et al. The mean estimated [trans fat] content of the seven control diets was 3ï¿½0 [% of calories] (range 1ï¿½5–9ï¿½6 [%]).
...the displacement of [trans fat], rather than the substitution of mixed n-3/n-6 [polyunsaturated fat] for [saturated fat], may account for some or all of the 22% reduction in non-fatal [heart attack] death in our meta-analysis. By contrast, the increased [heart attack] risks from n-6 specific [polyunsaturated fat] diets in our meta-analysis may be underestimated as n-6 [polyunsaturated fat] also replaced substantial quantities of [trans fat] (Table 3). The consistent trends towards increased [heart attack] risk of n-6 specific [polyunsaturated fat] diets may have become significant if the n-6 [polyunsaturated fat] replaced only [saturated fat], instead of a combination of [saturated fat] and [trans fat].
In other words, it looks like trans fat is probably the issue, not animal fat, but these trials replaced both simultaneously so we can't know for sure. I will note here that trans fat does not generally promote atherosclerosis (thickening and hardening of arteries) in animal models, so if it does truly increase heart attack risk as many studies suggest, it's probably through a mechanism that is independent of atherosclerosis.

The article also contains an excellent discussion of the Finnish mental hospital trial (5, 6) and why it was excluded from the meta-analysis, in which Dr. Ramsden and colleagues point out major design flaws, some of which I was not aware of. For example, trans fat intake was on average 13 times higher in the control groups than in the experimental groups. In addition, one of the control groups received more than twice as much of the antipsychotic drug thioridazine, which is known to be highly toxic to the heart, as any other group. Ouch. I'm glad to see this study finally discussed in an open and honest manner. I discussed my own problems with the Finnish trial in an earlier post (7).

I was also glad to see an open discussion of the Oslo Diet-heart study (8), in which diet changes led to a reduction in heart attack risk over five years. Dr. Mozaffarian and colleagues included it in their analysis as if it were a controlled trial in which animal fat was replaced by seed oils only. In reality, the investigators changed many variables at once, which I had also pointed out in my critique of Dr. Mozaffarian's meta-analysis (9). Here's what Dr. Ramsden and colleagues had to say about it:
First, experimental dieters were instructed to substitute fish, shellfish and ‘whale beef’ for meats and eggs, and were actually supplied with ‘considerable quantities of Norwegian sardines canned in cod liver oil, which proved to be popular as a bread spread’(32)... Second, the experimental group consumed massive amounts of soybean oil, which provided large quantities of both LA (15ï¿½6 en %) and ALA (2ï¿½7 en %). ALA consumption was about 4ï¿½5 times average US intake(42), or about twelve typical flax oil pills (1 g pill ï¿½ 560 mg ALA) per d. In addition, the fish and cod liver oil consumption provided Oslo (598N latitude) dieters with 610 IU (15ï¿½25 mg) of daily vitamin D3, recently linked to lower blood pressure, plaque stabilisation, and reduced [heart attack risk] (64). Furthermore, experimental dieters were encouraged to eat more nuts, fruits, and vegetables; to limit animal fats; and to restrict their intake of refined grains and sugar.
trans fat intake was also reduced substantially by excluding margarine in the experimental group. Other review papers have used this trial as a justification to replace animal fat with seed oils. Hmm... The only reason they get away with this is because the trial was published in 1966 and almost no one today has actually read it.

One criticism I have of Dr. Ramsden's paper is that they used the Oslo trial in their analysis, despite the major limitation described above. However, they were extremely open about it and discussed the problem in detail. Furthermore, the overall result would have been essentially the same even if they had excluded the Oslo trial from the analysis.

Overall, the paper is an excellent addition to the literature, and I hope it will bring a new level of sophistication to the dialogue on dietary prevention of cardiovascular disease. In the meantime, brace yourselves for an avalanche of criticism from the seed oil brigade.

* Guidelines that determine which studies to include in the analysis. For example, you want to exclude any study that wasn't randomized, because it will not be interpretable from a statistical standpoint. You also want to exclude trials where major variables differ between groups besides the specific variable you're trying to test. The Finnish mental hospital trial fails by both criteria.

Stephan has also had a go at this.
Please go to his blog for active links and some interesting comments.

Ted_Hutchinson · ï¿½ #3 ï¿½ 12-04-2010, 08:38 AM

Meta-analysis Reveals “Heart Healthy Omega-6 Fat” Increases Risk of Heart Disease Here is a link to Evelyn's article but this is located on her Omega 6 site (it wasn't working earlier) and this will be where her follow up post will appear. I'll be keeping watching with interest and post a link when it appears. But you may like to see that article in the context of her previous research on the topic.

Ted_Hutchinson · ï¿½ #4 ï¿½ 12-05-2010, 06:30 AM

problems with the American Heart Association's "Eat Your Omega-6 Fats" Advisory - Meta-analysis Reveals “Heart Healthy Omega-6 Fat” Ups Risk of Heart Disease Bit of related backstory to the Evelyn Tribole article that may interest.

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