Corrections to the New Review Paper on Dietary Fat and Cardiovascular Risk

The meta-analysis by Chowdhury et al. raised quite a furor from certain segments of researchers and the popular media.  I find this reaction interesting.  I usually write about obesity, which is a topic of great interest to people, but my post about the review paper received more than twice my usual traffic.  People whose findings or opinions are questioned by the paper are aggressively denouncing it in the media, even calling for retraction (1).  This resembles what happens every time a high-profile review paper is published that doesn't support the conventional stance on fatty acids and health (e.g., Siri-Tarino et al. [2], which despite much gnashing of teeth is still standing*).  I'm not sure why this issue in particular arouses such excitement, but I find it amusing and disturbing at the same time.  This kind of reaction would be totally out of place in most other fields of science, where aggressive public media outbursts by researchers are usually frowned upon.

As it turns out, the critics have a point this time.  Significant errors were uncovered in the original version of the meta-analysis, which have been corrected in the current version (3).  These include the following two errors, one of which alters the conclusion somewhat:

• The outcome of one observational study on omega-3 fatty acids was reported as slightly negative, when it was actually strongly positive.  This changes the conclusion of the meta-analysis, making it somewhat more favorable to omega-3 consumption for cardiovascular protection.
• The authors left out two studies on omega-6 fatty acids.  These didn't change the overall conclusions on omega-6.

Overall, the errors had relatively little impact on the analysis, and the only meaningful effect of correcting them was a more favorable result for omega-3 fatty acids.  Some have suggested that the presence of errors in the analysis means that the whole thing is unreliable-- who knows what other errors may be present, and the paper should be retracted with much fanfare (4).  I agree that the errors suggest a less-than-rigorous approach by the authors.  However, the authors corrected the mistakes that were pointed out, and they had a relatively small impact on the overall findings.  Unless more substantial errors are uncovered, I don't see the point of complaining about the possibility that additional errors may exist.

Another limitation of the paper was brought up in the comments on my last post about it.  The paper only considered randomized trials in which people supplemented with omega-3 or omega-6 fatty acids, not those in which one type of fat is replaced by another, which are called "dietary fat modification" trials.  This is a significant limitation and I'm not sure why they decided to omit those studies.

Dietary fat modification usually means reducing the intake of saturated and trans fats, while increasing the intake of polyunsaturated omega-6 and/or omega-3 fats**.  One of the most comprehensive meta-analyses on dietary fat modification was conducted by the Cochrane Collaboration (5).  Cochrane has a well-earned reputation for rigorous meta-analyses.  Its latest meta-analysis concluded the following:

• Dietary fat modification significantly reduced the risk of cardiovascular events by 14 percent.
• Dietary fat modification had no significant impact on cardiovascular mortality or total mortality.
• Low-fat diets had no impact on any cardiovascular outcome.

According to this meta-analysis, the dietary fat modification trials have identified a small but statistically significant effect on cardiovascular risk.  It's important to note the limitations of the Cochrane analysis:

• It included some trials, such as Oslo Diet-Heart, that modified a number of dietary variables besides fat.  This means that the results actually pertain to the modification of dietary fat and other foods.
• In many of these trials, participants decreased intake of saturated and trans fats simultaneously, and increased intake of polyunsaturated omega-6 and/or omega-3 fats (6).  Because there were so many variables changing, it's impossible to attribute effects to any individual type of fat.  
• It did not distinguish between interventions that replaced saturated/trans fats with only omega-6 fats, and those that increased omega-3 in addition.  Two interesting meta-analyses by Dr. Chris Ramsden and colleagues have suggested that this is an important distinction: trials that replaced saturated/trans fat with omega-6 alone didn't reduce risk (and may even have increased risk), while those that replaced it with oils containing omega-3 did reduce risk (6, 7).
• The trials this meta-analysis is based on lasted years, but they don't necessarily represent what would happen if you followed the same dietary pattern for a lifetime, beginning with people who are young and healthy at baseline.  It's likely that any effects would be exaggerated over a longer period of time.

In the end, I think all of these meta-analyses are problematic.  Meta-analyses are supposed to be the highest form of evidence; the final word.  But it turns out that the devil's in the details.  Depending on what you include or exclude, how you group the studies, and how you interpret the results, they can lead to different conclusions.  Furthermore, since they're narrowly focused on specific outcomes, they don't necessarily tell us what we want to know about overall health and well-being.  For example, a food that causes malabsorption might lead to a positive outcome in a weight loss trial, but that doesn't make it healthy in the broader sense.

In my view, the most important question is "what foods should I eat"?  The answer depends on the individual, but here are my general opinions.  Eating synthetic trans fat is probably a bad idea, and it's generally found in low-quality processed food anyway.  Refined seed oils like corn and soybean oil are the nutritional equivalent of white sugar, oxidize during high-heat cooking, and also tend to be found in low-quality processed food, making them a poor choice.  I haven't seen much evidence that makes me concerned about eating the fat naturally contained in meat and dairy, so I view those as acceptable, in moderation.  Nuts and wild seafoods seem to be healthy, whether or not that relates to their fatty acid profile, so it makes sense to eat them regularly.  Extra-virgin olive oil appears to be one of the healthiest fats, so it's logical to gravitate toward it as the default added fat.

I question how much these analyses and re-analyses of dietary fat modification trials have contributed to our understanding of what we should eat.  The bulk of the evidence, including from diet modification trials, suggests that we get the best results by focusing on overall diet quality rather than specific fatty acids.

* The primary critiques were 1) that the data were over-adjusted because some of the data had been pre-adjusted for circulating cholesterol levels, and 2) Dr. Ronald Krauss has received funding from the dairy industry.  Further analysis by Dr. Krauss's team confirmed that the result was the same whether one considered studies that had been adjusted for cholesterol, or those that had not.  Dr. Krauss was actually not receiving funding from the dairy industry at the time he wrote and published the paper, but in any case this argument is weak unless specific instances of bias can be identified in the paper.

** The role of trans fats tends to be overlooked in these meta-analyses.  Typically, results are attributed to replacing saturated fat with polyunsaturated fat, when in fact trans fat was also replaced.  If we believe trans fats are harmful to cardiovascular health, then this could plausibly account for the observed effects.  Dr. Ramsden has a great discussion of this issue in one of his papers (6).