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.

The Lyon Diet-Heart Study: Background

To appreciate the full significance of the Lyon diet-heart study, we have to go back in time a bit. We're off to 1982, the year the U.S. National Heart, Lung and Blood Institute published the results of their massive study, the Multiple Risk Factor Intervention Trail (MRFIT).

By 1982, the idea of the "prudent diet" was well ingrained in American medicine, despite a lack of direct evidence to support it, and even a certain amount of evidence at odds with it (such as the ill-fated Anti-Coronary Club trial). The prudent diet was designed to reduce the risk of heart attack, and suggests reducing total fat, saturated fat and cholesterol intake, while increasing consumption of vegetables, whole grains, fruit and fiber. Some versions of the diet replace saturated fat with polyunsaturated vegetable oils.

MRFIT involved 12,866 men at high risk of heart attack, making it one of the largest controlled trials of all time. Half of the group were told to keep doing what they were doing, under medical supervision, and the other half were given intense diet and lifestyle counseling. The intervention group was counseled to quit smoking and reduce their consumption of saturated fat and cholesterol, and increase polyunsaturated vegetable oil consumption.

After 6 years, 46% of the intervention group had quit smoking, compared to 29% in the control group. The intervention group reduced their cholesterol intake by 40% and their saturated fat intake by more than one-fourth, and increased their consumption of polyunsaturated fat (omega-6) by one third relative to the control group (source).

The results? After seven years, total mortality was 41.2 per 1,000 in the intervention group and 40.4 in the control group, a difference that was not even close to statistically significant. There were also no significant differences in heart attack rate or heart attack death rate. The authors and their apologists tried to wiggle out of the obvious conclusion through an avalanche of slippery math and editorials.

The results were mirrored by a later intervention trial published in 2006, the Women's Health Initiative dietary modification trial. This one was even larger, involving 48,835 postmenopausal women! This was another test of the prudent diet, in which participants were intensively counseled to

reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d.

After 6 years, the intervention group was eating 22% less fat, 23% less saturated fat, 20% less cholesterol, 15% more carbohydrate, 22% more fruits and vegetables, and slightly more fiber and whole grains than the control group. LDL dropped a bit in the intervention group.

I think you know what's coming...

Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women...

Oh and you forgot to mention, 4.9% of women died in the intervention group as opposed to 5.0% in the control group. A "minor detail" that I couldn't find in the paper so I had to look up elsewhere. The study also showed that the diet modifications didn't reduce the incidence of breast or colorectal cancer, two of the most common cancers. RIP, prudent diet. Although it still seems to be struggling along, despite the beating. Another set of editorials appeared claiming that the diet didn't work because it wasn't extreme enough. How far do we have to move the goalposts before we give up?

There was one interesting finding that came out of MRFIT, which foreshadowed the result of the Lyon trial. MRFIT participants eating the most omega-3 from fish were at a 40% lower risk of coronary heart disease and a 22% lower risk of dying of any cause. This was not part of the intervention, so it doesn't necessarily reflect cause and effect. For that, we'll have to look at the Lyon trial.