Good Diet, Bad Study
By Dr. Barry Sears
As the creator of the Zone Diet, I am a strong believer in the Mediterranean diet
as a lifetime dietary program for good health. In fact, the Zone Diet can be
considered to be the evolution of the Mediterranean diet as it provides even
greater anti-inflammatory benefits. That being said, this week’s New England
Journal of Medicine contained an article on using the Mediterranean diet with
high-risk cardiovascular patients that got great press based on some really poor
science (1). Let’s get to the bad science first.
The researchers compared two “Mediterranean” diets (one with extra nuts and
the other with extra olive oil) to a low-fat diet. Unfortunately, they were unable
to get the subjects to follow a low-fat diet. If you are a follower of Dean Ornish,
then a low-fat diet means less than 10% of your calories coming from fat. Using
that definition of a low-fat diet, you have to throw out one-third of the subjects
because they couldn’t reduce their fat intake below 37% of total calories. In fact,
at the end of this five-year study, the percentages of protein, carbohydrate, and
fat in the diets of all three groups were approximately the same. As a result, you
are left with a study with two groups of subjects being compared to another
group of subjects who really didn’t change their diet that much.
Even Dean Ornish pointed this out in his rebuttal blog in the Huffington Post to
this study (2). He wrote that if people had followed his low-fat diet, then the
results would have been much different. Well, actually when high-risk
cardiovascular patients did follow his diet in a study done 15 years ago, those on
his low-fat diet had twice the deaths compared to those in the control group (3).
So maybe it’s a good thing that the low-fat group couldn’t follow the prescribed
low-fat diet.
The reason for adverse effects of a low-fat, low-protein, very high-carbohydrate
diet for cardiovascular patients is quite clear. Those subjects following his highcarbohydrate, low-fat, and low-protein diet developed insulin resistance as
evidenced by a significant increase in their triglyceride-to-HDL ratio (3). If you
already have had a heart attack, then an increase in insulin resistance and the
accompanying increase in inflammation are almost certain to push you over the
edge.
If you really dig deeper into the supplemental material (Table S7 to be exact) of
this article (as most journalists neglected to do), you are remarkably unimpressed
by the changes in the diet over a five-year period except that the people who got
free olive oil and free nuts were consuming more free olive oil and free nuts than
those who were not getting free food.
Now, back to the clinical results -- a strange brew of stroke, heart attack, and
death. Usually when you include a lot of different clinical end points as your
primary goal, it means you are not very confident about seeing any real striking
clinical benefit. Stroke is primarily associated with high blood pressure, whereas
heart attack is associated with the rupture of small vulnerable plaques leading to
blockage of the coronary arteries. I personally like death as a clinical end point
since you can’t cheat on its definition, thus making it harder to manipulate your
statistics to prove your point.
So let’s look at the individual clinical endpoints. There was a reduction in
strokes that was statistically significant. Unfortunately, there was no statistically
significant reduction in either heart attacks or death. For such a large study,
these clinical results are not too impressive. Maybe if the researchers had
actually gotten the low-fat group to reduce their fat intake to less than 10% of
calories (instead of going from 39% to 37% of calories), there might have been
more deaths in that group, which would have made the other two Mediterranean
diet groups look better.
Virtually every cardiovascular researcher knows that fatty acid composition of
the plasma is an important factor in the prediction of future cardiovascular
events. Unfortunately, the authors of the New England Journal of Medicine article
apparently didn’t think so. Obviously, they measured one fatty acid (alpha
linolenic acid) in Figure 5S (again buried deep in the supplemental material), but
somehow forgot to report the other 34 fatty acids also found in the plasma. Two
of the most important of these unreported fatty acids would have included
arachidonic acid (AA) and eicosapentaenoic (EPA). The AA/EPA ratio in the
blood is the best marker of cellular inflammation that drives heart disease (4).
You would think inclusion of information on this ratio (or at least providing the
fatty acid levels) would be important since a far larger JELIS study demonstrated
that the lowering of the AA/EPA ratio resulted in a significant reduction of
cardiovascular events (5).
In contrast to this poorly executed study, there exists a far more powerful study
conducted nearly 20 years ago on the benefits of a stricter Mediterranean diet.
This is was the Lyon Diet Heart Study (6). The primary clinical difference
between this new study and older Lyon Diet Heart Study is that the Lyon Diet
Heart Study generated a 65% reduction in overall cardiovascular mortality, a
complete reduction in cardiac sudden death, and 44% reduction in all-cause
mortality (6,7). Those are clinical end points to get excited about. On the other
hand, this New England Journal of Medicine article showed no impact on mortality.
The only striking difference between the two groups in the Lyon Diet Heart
Study was the restriction of omega-6 fatty acids in the experimental group. You
find omega-6 fatty acids in vegetable oils like corn, safflower, and sunflower oils.
They accomplished this dietary change by giving the subjects in the experimental
groups margarines rich in omega-3 fats and trans fats. Although there was a
dramatic decrease in death between the two groups in the Lyon Diet Heart Study,
there were no differences in weight, BMI, blood pressure, cholesterol (good and
bad), and blood lipids between the two groups. In other words, all the usual
suspects in heart disease were eliminated. The only differences between the two
groups were in the fatty acids, both linoleic acid and the AA/EPA ratio. If you
again go back to bowels of the recent New England Journal article (in
supplemental Table S7), you find out that the levels of linoleic acid (an omega-6
fatty acid) as analyzed from dietary records of the subjects was between 5 and
6% in both of the Mediterranean diets. In the Lyon Diet Heart Study, the
investigators were able to reduce to the linoleic levels to 3.6%, which is similar to
levels found in the Japanese (actually Okinawans), who have the lowest
cardiovascular mortality in the developed world (8). The subjects in the control
group of the Lyon Diet Heart Study had a nearly 50% higher level of linoleic acid
in their blood compared to the experimental group (8). However, those subjects
following the “Mediterranean” diets in the new study had even higher levels of
linoleic acid than those in the control group of the Lyon Diet Heart Study. That
is the most likely reason there wasn’t any change in cardiovascular mortality or
overall mortality in the New England Journal of Medicine study. Unlike this more
“modern” study, the Lyon researchers further demonstrated that the AA/EPA
ratio was reduced by some 30% (from 9 to 6.2) in the active group compared to
the control group, and this resulted in a 65% reduction of cardiovascular death.
Bottom line, unless you dramatically reduce omega-6 intake by reducing your
consumption of vegetable oils (such as corn, soy and safflower oils), you will not
get clear-cut clinical results (like reduction in death) no matter how much hype
the media give to the research.
As I said earlier, the Zone Diet can be considered to be the evolution of the
Mediterranean diet because it represents a superior dietary program to control
inflammation, the true underlying cause of heart disease. This is because the
Zone Diet dramatically reduces white carbohydrates (pasta, bread, rice, and
potatoes) and replaces them with increased amounts of colorful carbohydrates
(vegetables and fruits). Unlike the New England Journal of Medicine article where
the subjects were consuming about 5 servings a day of vegetables and fruits, the
Zone Diet recommends 10 servings per day. Rather than keeping the linoleic
acid content at 6% of the calories (the American Heart Association recommends
10-15%) or even at the 3.6% level as in the Lyon Diet Heart Study, the Zone Diet
recommends fewer than 2% of total calories should consist of linoleic acid. Like
the JELIS study, the Zone Diet recommends extra supplemental of omega-3 fatty
acids to reduce the AA/EPA ratio to 1.5 or less.
Although the jury may still be out on the Mediterranean diet (especially after this
poorly executed study) for the primary prevention of heart disease, the data from
secondary prevention studies (5-7) strongly suggest that the Zone Diet may be
the dietary approach you want to follow if reducing mortality is your personal
clinical end point.
References
1. Estuch R et al. “Primary prevention of cardiovascular disease with a
Mediterranean diet.” N Engl J Med 368: doi10.1056/NEJMoa1200303 (2013)
2. Ornish D. “Does a Mediterranean diet really beat a low-fat for health?”
HuffPost Healthy Living Feb 25 (2013)
3. Ornish D et al. “Intensive lifestyle changes for reversal of coronary heart
disease.” JAMA 280: 2001-2007 (1998)
4. Sears B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005)
5. Yokoyama M et al. “Effects of eicosapentaenoic acid on major coronary events
in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded
endpoint analysis.” Lancet 369: 1090-1098 (2007)
6. de Lorgeril et al. “Mediterranean alpha-linolenic-rich diet in secondary
prevention of coronary heart disease.” Lancet 343: 1454-1459 (1994)
7. de Lorgeril et al. “Mediterranean diet, traditional risk factors, and the rate of
cardiovascular complications after myocardial infarction.” Circulation 99: 779785 (1999)
8. Kagawa Y et al. “Eicosapolyenoic acids of serum lipids of Japanese islanders
with low incidence of cardiovascular disease.” J Nutr Sci Vitaminol 28: 441-453
(1982)