Applied Nutrigenomics
Where Genes and Food Come Together
by Dr. John M. Berardi, PhD, CSCS

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. El-Sohemy

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.

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.

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.

"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.

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.

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

Dr. El-Sohemy: 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.

Berardi: 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?

Dr. El-Sohemy: 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.

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

Dr. El-Sohemy: 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.

Would that explain why we're now craving a drink?

Berardi: 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?

Dr. El-Sohemy: 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.

Berardi: What are we talking about here? What's nanoscience and how can it impact nutrient delivery?

Rez-V is now made in a new nano-dispersed capsule.

Dr. El-Sohemy: 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.

Berardi: And which direction is your research team headed?

Dr. El-Sohemy: 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.

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

Dr. El-Sohemy: My pleasure. Will do!

About Dr. El-Sohemy

Dr. Ahmed El-Sohemy is an internationally-recognized researcher in the field of nutrigenomics. He is an Associate Professor and Canada Research Chair in Nutrigenomics in the Department of Nutritional Sciences, Faculty of Medicine, at the University of Toronto.

In 2004, he was voted one of the top 10 people to watch by the Toronto Star, Canada's largest daily newspaper. He has consulted for industry and government agencies and serves as an expert scientific reviewer for dozens of scientific and medical journals, national granting agencies, and international advisory panels.

About Dr. Berardi

Dr. John Berardi, CSCS, is a world-renowned author, speaker, and consultant to a number of elite athletic programs. In addition he's an Assistant Adjunct Professor at the University of Texas at Austin. For more information about Dr. Berardi and his nutrition programs for both athletes and recreational exercisers, check out www.precisionnutrition.com.

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