summarize: These are more rigorous than epidemiology, and they offer some ability to
infer causality thanks to the process of randomization, but they too are often
flawed. There’s a trade-off between sample size, study duration, and control.
To do a long study in a large group of subjects, you essentially have to trust
that they are following the prescribed diet, whether the Big Mac diet in our
hypothetical example from above, or a simple low-fat diet. If you want to
ensure that your subjects are actually eating the diet, you need to feed each
subject, observe them eating, and keep them locked in the metabolic ward of
a hospital (to be sure they are not eating anything else). All of this is doable,
but only for a handful of subjects for a few weeks at a time, which is not
nearly a large enough sample or long enough duration to infer anything
beyond mechanistic insights about nutrients and health.
These studies make pharmaceutical studies seem simple. Determining
whether pill X lowers blood pressure enough to prevent heart attacks requires
only that study subjects remember to take their pill every day for however
many months or years, and even that simple compliance poses a challenge.
Now imagine trying to ensure that study subjects lower their dietary fat
content to no more than 20 percent of total calories and consume at least five
servings of fruits and vegetables daily for a year. In fact, I’m convinced that
compliance is the key issue in nutrition research, and with diets in general:
Can you stick to it? The answer is different for almost everyone. This is why
it’s so difficult for experiments to answer the central questions about the
relationship between diet and disease, no matter how big and ambitious they
are.
One classic example of a well-intended nutrition study that created more
confusion than clarity is the Women’s Health Initiative (WHI), an enormous
randomized controlled trial that was meant to test a low-fat, high-fiber diet in
nearly fifty thousand women. Begun in 1993, it lasted eight years and cost
nearly $750 million (and if it sounds familiar, that is because of the study’s
highly publicized other arm, discussed earlier, which looked at the effects of
hormone replacement therapy on older women). In the end, despite all this
effort, the WHI found no statistically significant difference between the lowfat and control diet groups in terms of incidence of breast cancer, colorectal
cancer, cardiovascular disease, or overall mortality.
[*6]
Many people, myself included, argued that the results of this study
demonstrated the lack of efficacy of low-fat diets. But in reality, it probably
told us nothing about a low-fat diet because the “low-fat” intervention group
consumed around 28 percent of their calories from fat, while the control
group got about 37 percent of their calories from fat. (And that’s even
assuming the investigators were able to be remotely accurate in their
assessment of what the subjects actually ate over the years, a big assumption.)
So this study compared two diets that were pretty similar, and found that they
had pretty similar outcomes. Big surprise. Nevertheless, flawed as it was, the
WHI study has been fought over for years by partisans of different ways of
eating.
Just as an aside, the WHI study does provide a clear example of why it is
so important to evaluate any intervention, nutritional or otherwise, through
the lens of efficacy versus effectiveness. Efficacy tests how well the
intervention works under perfect conditions and adherence (i.e., if one does
everything exactly as prescribed). Effectiveness tests how well the
intervention works under real-world conditions, in real people. Most people
confuse these and therefore fail to appreciate this nuance of clinical trials.
The WHI was not a test of the efficacy of a low-fat diet for the simple reasons
that (a) it failed to test an actual low-fat diet, and (b) study subjects did not
adhere to the diet perfectly. So it can’t be argued from the WHI that low-fat
diets do not improve health, only that the prescription of a low-fat diet, in this
population of patients, did not improve health. See the difference?
—
That said, some clinical trials have provided some useful bits of knowledge.
One of the best, or least bad, clinical trials ever executed seemed to show a
clear advantage for the Mediterranean diet—or at least, for nuts and olive oil.
This study also focused on the role of dietary fats.
The large Spanish study known as PREDIMED (PREvención con DIeta
MEDiterránea) was elegant in its design: rather than telling the nearly 7,500
subjects exactly what they were supposed to eat, the researchers simply gave
one group a weekly “gift” of a liter of olive oil, which was meant to nudge
them toward other desired dietary changes (i.e., to eat the sorts of things that
one typically prepares with olive oil). A second group was given a quantity of
nuts each week and told to eat an ounce per day, while the control group was
simply instructed to eat a lower-fat diet, with no nuts, no excess fat on the
meat they did eat, no sofrito (a garlicky Spanish tomato sauce with onions and
peppers that sounds delicious), and weirdly, no fish.
The study was meant to last six years, but in 2013 the investigators
announced that they had halted it prematurely, after just four and a half years,
because the results were so dramatic. The group receiving the olive oil had
about a one-third lower incidence (31 percent) of stroke, heart attack, and
death than the low-fat group, and the mixed-nuts group showed a similar
reduced risk (28 percent). It was therefore deemed unethical to continue the
low-fat arm of the trial. By the numbers, the nuts-or-olive-oil
“Mediterranean” diet appeared to be as powerful as statins, in terms of
number needed to treat (NNT), for primary prevention of heart disease—
meaning in a population that had not yet experienced an “event” or a clinical
diagnosis.
[*7]
It looked like a slam dunk; it’s rare when investigators can report hard
outcomes like death or heart attack, as opposed to simple weight loss, in a
mere dietary study. It did help that the subjects already had at least three
serious risk factors, such as type 2 diabetes, smoking, hypertension, elevated
LDL-C, low HDL-C, overweight or obesity, or a family history of premature
coronary heart disease. Yet despite their elevated risk, the olive oil (or nuts)
diet had clearly helped them delay disease and death. A post hoc analysis of
PREDIMED data also found cognitive improvement in those allocated the
Mediterranean-style diet(s), versus cognitive decline in those allocated the
low-fat diet.
But does that mean a Mediterranean diet is right for everyone, or that
extra-virgin olive oil is the healthiest type of fat? Possibly—but not
necessarily.
To me, perhaps the most vexing issue with diet and nutrition studies is the
degree of variation between individuals that is found but often obscured. This
is especially true in studies looking mostly or entirely at weight loss as an end
point. The published studies report average results that are almost always
underwhelming, subjects losing a few pounds on average. In reality, some
individuals may have lost quite a bit of weight on the diet, while others lost
none or even gained weight.
There are two issues at play here. The first is compliance: how well can
you stick to the diet? That differs for everyone; we all have different behaviors
and thought patterns around food. The second issue is how a given diet affects
you, with your individual metabolism and other risk factors. Yet these are too
often ignored, and we end up with generalizations about how diets “don’t
work.” What that really means is that diet X or diet Y doesn’t work for
everyone.
Our goal in the next chapter is to help you figure out the best eating plan
for you, as an individual. To do that, we must move beyond labels and dive
into nutritional biochemistry.