Applied Nutrigenomics
Where Genes and Food Come Together - Part 1
by Dr. John M. Berardi, PhD, CSCS
First published at www.t-nation.com

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.

John Berardi: 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?

Dr. Ahmed El-Sohemy: 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.

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.
Berardi: 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?

Dr. El-Sohemy: 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.

Berardi: 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?

Dr. El-Sohemy: 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.

Berardi: 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?

Dr. El-Sohemy: 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.

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

Dr. El-Sohemy: 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).

Berardi: How do people make sense of this dichotomy?

Dr. El-Sohemy: 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.

Berardi: 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?

Dr. El-Sohemy: 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.

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.

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

Dr. El-Sohemy: 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.

SOURCE: http://www.precisionnutrition.com/members/showthread.php?t=10829