Sunday, June 7, 2009

The Lyon Diet-Heart Study

Now that we have the proper context, it's time to dig into the Lyon Diet-Heart trial, one of the most important and misunderstood diet trials of all time.

The trial enrolled 605 middle-aged French men and women who had previously suffered a heart attack. This is called a "secondary prevention" trial because it's designed to prevent a second heart attack. The advantage of secondary prevention trials is that they can be smaller, because men who have already had a heart attack are at a much higher risk of having another. This increases your statistical power. The disadvantage is that the participants aren't necessarily representative of the population at large.

Participants were divided into a control group and an intervention group. The control group "received no dietary advice from the investigators but nonetheless were advised to follow a
prudent diet by their attending physicians". Ah, the prudent diet rears its ugly head once again. In a later paper, they describe the prudent diet they used in a bit more detail:
[The control subjects] were expected to follow the dietary advice given by their attending physicians, similar to that of step I of the prudent diet of the American Heart Association.
And what exactly is this prudent diet? It was created by the National Cholesterol Education Panel, that very conflicted organization I've written about before. Step I is now defunct, having given way to the next generation of NCEP guidelines in 2000. Here's a summary of the old Step I from the American Heart Association's website:
The Step I diet restricted total fat to no more than 30 percent of total calories, saturated fat to no more than 10 percent of total calories, and cholesterol to less than 300 mg/day. It was intended as the starting point for patients who had high cholesterol levels.
This is an important point: the Lyon Diet-Heart trial wasn't an ordinary trial comparing the average person's diet to a different diet. It was a bare-knuckle showdown between the prudent diet and a modified version of the Mediterranean diet! I believe that's part of the reason it was rejected by the prestigious New England Journal of Medicine, although there's another reason I'll get to later. The intervention group received different advice:
Patients in the experimental group were advised by the research cardiologist and dietician, during a one-hour-long session, to adopt a Mediterranean-type diet: more bread, more root vegetables and green vegetables, more fish, less meat (beef, lamb, and pork to be replaced with poultry), no day without fruit, and butter and cream to be replaced with margarine supplied by the study.

Because the patients would not accept olive oil- traditional to the Mediterranean diet- as the only fat [because French people use more butter than olive oil- SG], a rapeseed (canola) oil-based margarine (Astra-Calve, Paris, France) was supplied free for the whole family to experimental subjects. This margarine had a composition comparable to olive oil [mon oeil- SG] with 15% saturated fatty acids, 48% oleic acid but 5.4% 18:1 trans. However, it was slightly higher in linoleic [omega-6- SG] (16.4 vs 8.6%) and more so in alpha-linolenic acid [omega-3- SG] (4.8 vs 0.6%), a fatty acid markedly higher (3 fold) in the plasma of the Cretan cohort in the Seven Country study compared to that of Zutphen (Netherlands).

The oils recommended for salads and food preparation were rapeseed and olive oils exclusively. Moderate alcohol consumption in the form of wine was allowed at meals. At each subsequent visit of the experimental patients, a dietary survey and further counseling were done by the research dietician.
After five long years of these brutal diets, participants in the intervention ("Mediterranean") group were eating slightly less total fat, 29% less saturated fat, 32% less cholesterol, a bit more bread, legumes, fruit, vegetables and fish, compared to the control (prudent diet) group. They were also eating less meat and much less butter and cream, although cheese consumption was the same between groups. French people know better than to give up their cheese!

So far, these changes are not unique. They're similar to the interventions in the ineffective MRFIT and WHI trials in the last post. Here's where it gets interesting. The intervention group ate three times as much omega-3 alpha-linolenic acid as the control group, and 32% less omega-6 linoleic acid. The ratio was 20 : 1 linoleic acid : alpha-linoleic acid in the control group, and 4.4 : 1 in the intervention group. This was due to the combination of a low-fat diet and the canola oil goop they were provided free of charge.

But it gets even better. The intervention group reduced their omega-6 linoleic acid intake to 3.6% of calories, below the critical threshold of 4%. As I described in my
recent post on eicosanoid signaling, reducing linoleic acid to below 4% of calories inhibits inflammation, while increasing it more after it has already exceeded 4% has very little effect if omega-3 is kept low*. This is a very important point: the intervention group didn't just increase omega-3. They decreased omega-6 to below 4% of calories. That's what sets the Lyon Diet-Heart trial apart from all the other failed diet trials.

After five years on their respective diets, 3.4% of the control (prudent diet) group and 1.3% of the intervention ("Mediterranean") group had died, a 70% reduction in deaths. Cardiovascular deaths were reduced by 76%. Stroke, angina, pulmonary embolism and heart failure were also much lower in the intervention group. A stunning victory for this Mediterranean-inspired diet, and a crushing defeat for the prudent diet!

There's a little gem buried in this study that I believe is the other reason it didn't get accepted to the New England Journal of Medicine: there was no difference in total cholesterol or LDL values between the control and experimental groups. The American scientific consensus was so cholesterol-centric that it couldn't accept the possibility that an intervention had reduced heart attack mortality without reducing LDL. The paper was accepted to the British journal The Lancet, another well-respected medical journal.

In the next post, I'll describe how we can benefit from the findings of the Lyon trial, and even surpass it, without having to resort to canola oil margarine.

*I admit 4% is somewhat arbitrary, but I think it's a good reference point based on the shape of the HUFA curve in this post.

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