Applied Nutrigenomics

Nutrigenomics: The study of how genes and nutrients
interact.

Until recently, I knew this field of science was an exciting
area that would someday change the future of nutrition, medicine,
and more.

However, in my mind all this crazy gene-nutrient stuff was still
wrapped up in mystery. It was the stuff futurists hypothesized
about rather than the stuff physicians, nutritionists, and health
experts could use every day.

Six months ago I was fortunate to sit in on a small-group
lecture led by one of the world's top nutrigenomics researchers,
Dr. Ahmed El-Sohemy. When I heard Dr. El-Sohemy speak, I realized
that I was wrong. With the completion of the human genome project
and the latest nutritional science, it's clear that nutrigenomics
is no longer the future of medicine. It's here today. And
it's being applied by cutting-edge health experts everyday.

As I sat in the audience, my neurons were firing like a fourth
of July light show. There was so much info flying around that my
pen couldn't move fast enough to keep up. I knew I had to sit down
to pick Dr El-Sohemy's brain. Here's what came out of our latest
conversation.

T Nation: Dr. El-Sohemy, thanks for agreeing to do this
interview. It's much appreciated and I know everyone reading will
be fascinated by your work.

A few months back, you presented some very interesting data
looking at how genomic information can impact our understanding of
nutrition and nutrient science. In other words, you talked about
how our genes can determine our responses to the food we eat, the
supplements we take, and more.

For those readers unfamiliar with this area of research, can you
briefly describe the field of nutrigenomics?

Nutrigenomics, sometimes called
nutritional genomics, investigates how the foods we eat interact
with our genes to affect our health. The questions we typically ask
are, "How much of each nutrient should a particular person
consume?" and, "What are the biological effects of a specific
supplement?"

There are basically two approaches that we use to investigate
such questions.

First, we look at how common variations found throughout the
human genome explain individual differences in response to dietary
intake. For example, this area of research explains why some people
can eat a high fat diet and have no problem with their cholesterol
levels while others experience the exact opposite
response.

Breakfast of champions for some, heart attack special for
others.

This line of research, sometimes referred to as nutrigenetics, enables us to understand why some individuals
respond differently than others to the exact same
nutrients.

The second approach that nutrigenomics researchers use is to
investigate how nutrients and bioactive components in food turn on
or off certain genes – these genes impacting important metabolic
and physiologic processes in the body.

For example, researchers have identified compounds found in
broccoli that switch on a specific gene that helps the body
detoxify some of the harmful chemicals we're sometimes exposed
to.

Of course, this line of research helps us understand the
mechanisms behind how food, and specific compounds within food, can
impact our health.

T Nation: This is really cool stuff, especially since people have
long proclaimed that when it comes to nutrition, "you gotta find
what works for you." Often times this means lots of trial and
error.

In essence, the field of nutrigenomics is helping to explain why you gotta find what works for you, as well as helping to
determine whatwill work for your genetic type.

Before getting deeper into your research, I'm curious. How does
someone like you get involved in the field of nutrigenomics? What's
your background?

I first became interested in this field about 10
years ago, which is before the term "nutrigenomics" was actually
coined. At the time, I was working on my PhD in nutritional
sciences and was researching the effects of cholesterol on cancer
using rodent models.

One of my experiments gave totally unexpected results. In fact,
they were completely the opposite of those published by other
researchers. It turned out, however, that the strain of rat that I
used metabolizes cholesterol quite differently than other strains
that were used in previous experiments.

The study design was virtually identical to previous ones, but
the only real difference was the genetic background of the animals.
I realized the importance of considering genetics when studying
nutrition and it occurred to me that genetic differences between
humans could also explain why some people respond differently than
others.

So I decided to take some genetics courses and complete a major
in molecular biology. After finishing my PhD at the University of
Toronto, I went to Harvard for a fellowship to pursue this type of
research in humans.

T Nation: As such, you're definitely a pioneer in the field. And
it's awesome that we have guys like you with extensive bio and
genetics backgrounds looking into some very important nutritional
questions.

Just how can our genes impact our personal responses to the
foods we eat and the drugs we take?

Well, to start with, we've known for a long time
that individuals respond differently to certain drugs. In fact,
much of the pioneering work in pharmacogenetics was done
decades ago at the University of Toronto.

But the concept of personalized medicine dates as far back as
480 BC when Hippocrates, the father of modern medicine, noted that
"Positive health requires a knowledge of man's primary constitution
and of the powers of various foods, both those natural to them and
those resulting from human skill."

The word "constitution" is a clear reference to our genetic
profile and the "foods resulting from human skill" can be seen as
the dietary supplements and functional foods we now have
available.

Just like with drugs, when it comes to the nutrients we take in
through our diets or the supplements we take, our genes can cause
us to respond differently from our neighbors.

Here's an example: Certain genes can affect the rate of
absorption, distribution, metabolism, or excretion of almost
everything we consume. And these differences can result in extreme
variability in how we respond.

The gene that I mentioned earlier, which can be activated by
compounds found in broccoli, is actually missing in about 20% of
the population. So some people won't benefit from the detoxifying
properties of broccoli, although they probably still benefit from
its antioxidant effects.

Understanding the basis of this variability will certainly help
us do a few things. First, it can help explain some of the
inconsistencies among previous studies that have linked nutrients,
supplements, and other bioactives to a number of health outcomes.
Second, it can help us understand how to eat or which supplements
to use based on our genetic profile.

T Nation: Indeed, I've read that based on genetic differences,
the physiological response to a certain drug or supplement could be
70-times different at the same dose between two individuals. While
this seems shocking, it does stand to reason.

For example, some people respond to creatine supplementation
with large performance improvements and increases in lean mass
while others have no response. From this, it's likely that one or
more of the steps – absorption, distribution, metabolism, or
excretion – are impacted by their different genotypes, leading to a
wide difference in response.

I know you're looking into this very thing with respect to
caffeine intake. What's your lab showing?

Last year, we published a study in the Journal
of the American Medical Association to demonstrate that in some
individuals, caffeinated coffee intake lowered the risk of heart
attacks. But in other individuals the same dose of caffeinated
coffee increased the risk of heart attacks.

T Nation: Let me guess. It had to do with the
genes.

That's right. Individuals who had what we call a
'slow' version of the gene CYP1A2 (a gene that breaks down caffeine
in the liver) have an increased risk of a heart attack when
increasing consumption of caffeinated coffee.

However, those who have the 'fast' version of CYP1A2, have a lower risk of heart attacks with moderate intakes of
caffeinated coffee (1-3 cups per day).

T Nation: How do people make sense of this
dichotomy?

These findings suggest that caffeinated coffee
only increases heart disease in those who have a limited capacity
to break down caffeine.

The reason why those with the 'fast' version of the gene might
benefit is because they can break down caffeine very rapidly,
getting rid of the caffeine while preserving the "healthy"
antioxidants in the coffee. It's these antioxidants, not the
caffeine, which might offer protection for the heart.

So, in the end, caffeine itself probably isn't good for anyone
in terms of heart disease. But, if you can get rid of it quickly
because you're a 'fast' metabolizer of caffeine, then you might
benefit from the other compounds in either coffee or tea, both of
which are pretty good sources of antioxidants.

By the way, being a 'fast' metabolizer for caffeine doesn't
necessarily make you a 'fast' metabolizer of any other dietary
factor. The enzymes coded by each gene are quite specific to the
compounds they metabolize.

T Nation: Unfortunately for me, I don't know my CYP1A2 genotype,
but I do love an occasional cup of espresso! How can I know if I'm
playing Russian roulette with my health every time I brew up a pot
of java?

Some people think they know they're 'slow'
metabolizers of caffeine because if they have a coffee in the
afternoon, it'll keep them up all night. But this just means that
caffeine binds more effectively to a specific receptor in the
nervous system, which is how caffeine acts as a
stimulant.

It doesn't tell you anything about how quickly caffeine is
broken down by the liver, which is the main organ that's
responsible for metabolizing caffeine. The only way to know if
you're a' fast' or 'slow' caffeine metabolizer is by having a DNA
test.

"Mike, you are not a slow caffeine
metabolizer."

My lab routinely runs these genetic tests using cells that are
easily obtained by swabbing the inside of your mouth. Although this
is done primarily for research purposes and for health care
practitioners, we're also trying to develop a test that doesn't
require the use of elaborate equipment needed to process and
analyze DNA.

T Nation: Aren't some progressive health centers doing this type
of genetic testing for patients? If so, any
recommendations?

I've heard about a company that claims to offer
the CYP1A2 test based on our published study, but I can't really
comment on how reliable their test is. They haven't done the
research that we have.

T Nation: In addition to caffeine, are there any other
interventions looking at how different genotypes respond to
different diets or nutritional supplements?

There are many interesting studies doing just
that. Examples include the ability of fish oil to lower blood
lipids, how saturated fat reduction affects plasma cholesterol
levels, or how certain phytochemicals can be more biologically
active in some individuals.

A few studies have shown that those who have a particular
version of the PPARg gene respond much more favorably to the blood
lipid lowering effects of fish oils. Some of these studies are
small and the results only preliminary, but exciting
nonetheless.

These kinds of studies mean we no longer have to play a guessing
game when trying to predict whether fish oils can lower our
blood lipids and reduce our risk of heart disease.

As for lowering your saturated fat intake, it turns out that
this is beneficial for the vast majority, but in some people who
have a particular version of the APOE gene, it actually has the
opposite effect.

Finally, green tea is known to have several beneficial
phytochemicals, but a number of studies are now showing that some
people break down these compounds more slowly and probably don't
need to consume as much to get the same benefits.

Don't need to consume much green tea? Gimme a
break.

T Nation: This is awesome stuff and it really calls into question
every piece of research done to date! After all, with
genetically-mixed subject populations, it's no wonder the nutrition
research can be quite inconsistent.

Now, I've heard you speak about how genes not only impact health
outcomes, but they can impact food preferences. What's being looked
at on that front?

Well, there are about two dozen genes that code
for bitter taste receptors on the surface of the tongue. And
variations in these genes could explain why some people find
certain foods like broccoli or cauliflower very bitter. Yet, others
find them much less bitter.

Genes can also affect the foods we select by affecting the
brain's reward system. In fact, different nutrients and food
bioactives have different effects on neurotransmitters like
dopamine and serotonin, both of which influence our mood and
behavior. And all of this is based on our genotype.

For example, my lab is currently investigating why some
individuals seem to crave sugars or carbohydrates more than others
and why caffeine improves mood in some people, but causes anxiety
in others.

T Nation: Which neurotransmitters are we talking about here with
respect to these carb and caffeine cravings?

Well, we're beginning to look at the gene that
codes for a major receptor for dopamine, which we think might
impact the mood response to a variety of foods. We're conducting
these studies at the moment and should start getting some results
over the next few months.

T Nation: This is really great stuff, and I'm sure we're just at
the tip of the iceberg here. Any predictions for other areas
researchers will be exploring in the near future and what they'll
find?

Well, I think there's still so much that we don't
understand in terms of how nutrients interact with genes to affect
health, fitness, and performance. In fact, we're only beginning to
appreciate the complexity of the human genome.

We used to think that any two individuals were 99.9% the same,
but it looks like we're probably much more different from one
another. As our understanding of the human genome improves, it
changes the types of questions we start asking about nutrition, and
it changes how we design our studies.

As for other areas of nutrition research, I think we're going to
start seeing some very interesting work involving the application
of nanoscience. This will involve changes to the delivery system of
nutrients and food bioactives.

T Nation: What are we talking about here? What's nanoscience and
how can it impact nutrient delivery?

Nanoscience deals with matter on an ultra-small
scale (1 nanometer is one-millionth of a millimeter).

If you take a particle and chop it up into much smaller pieces,
you increase the surface area without changing the actual amount. A
much larger surface area provides more space for chemical and
biological reactions to take place.

Depending on the size of the particles, the overall potency will
be very different. This means we might be able to use much smaller
quantities of supplements because we can use them more
efficiently.

T Nation: And which direction is your research team headed?

We have a number of projects aimed at identifying
the genetic factors that influence caffeine consumption behaviors,
as well as how genetic factors modify the various biological
effects of caffeine. We're also trying to identify the genes that
can explain preferences and aversions for specific foods and
flavors.

Also, my group is looking at identifying genetic variations that
predict responsiveness to vitamins and other essential nutrients.
We already have some exciting preliminary findings that we'll be
presenting at the Experimental Biology conference in San Diego in
April, 2008.

T Nation: Thanks Dr. El-Sohemy. Keep us informed about your
latest research.

My pleasure. Will do!