Source: The Guardian
Date: May 15, 2003

Eat right for your genotype

intelligent eating?

First it was smart drugs. Now it's smart diets.
Bruce Grierson on what your genes want you to eat

A trip to the diet doc, circa 2013. You prick your finger, draw a little blood and send it, with $100, to a consumer genomics lab in California. There, it's passed through a mass spectrometer for protein analysis and cross-referenced to your DNA profile. A few days later, you get an email message with your recommended diet for the next four weeks. It doesn't look too bad: lots of salmon, spinach, selenium supplements, bread with olive oil.

Your diet is uniquely tailored. It is determined by the specific demands of your genetic signature and perfectly balances your micro- and macro-nutrient needs. Sick days are a foggy memory. (Foggy memory itself is now treated with extracts of ginkgo biloba and a cocktail of omega-3 fatty acids.)

The appeal of this kind of laser-targeted diet intervention is hard to miss. If you turn out to be among the population whose cholesterol count doesn't react much to diet, you'll be able to go ahead and eat those bacon sandwiches. You'll no longer be spending money on vitamin supplements that do nothing for you; you'll take only the vitamins you need, in precisely the right doses. There's a real chance of extending your life - by postponing the onset of diseases to which you're naturally susceptible - without having to buy even a single book by Deepak Chopra. This is the promise - and the hype - of nutritional genomics, the second wave of personalised medicine to come rolling out of the Human Genome Project (after pharmacogenomics, or designer drugs). The premise is simple: diet is a big factor in chronic disease, responsible, some say, for a third of most types of cancer. Dietary chemicals change the expression of one's genes and even the genome itself. And - here's the key - the influence of diet on health depends on an individual's genetic makeup.

How does that work? Consider what happens, biologically, when we eat a meal. Until quite recently, most scientists thought food had basically one job: it was metabolised to provide energy for the cell. Indeed, that is what happens to most dietary chemicals - but not all. Some don't get metabolised at all; instead, the moment they're ingested, they peel off and become ligands - molecules that bind to proteins involved in "turning on" certain genes to one degree or another. A diet that's particularly out of balance, nutritional-genomics scientists say, will cause gene expressions that nudge us toward chronic illness unless a precisely-tailored "intelligent diet" is employed to restore the equilibrium.

Take genestein, a chemical in soy which attaches to oestrogen receptors and regulates genes. Individuals may have oestrogen receptors that react to genestein differently, helping to explain why two people eating the same diet can respond very differently - one maintaining weight, for example, and the other ballooning.

There is a buzz around nutritional genomics at the moment, which is partly a matter of timing. A sea change is underway in the approach scientists are taking to disease - they're looking less to nature or nurture alone for answers, and more to the interactive symphony of "systems biology" that nutrigenomics epitomises.

Chatter around this new science has been amplified by a controversy. The assumption of genetic markers that distinguish one ethnic group from another is at the philosophical heart of nutrigenomics. The idea of the biological relevance of race - even its very existence - is hotly debated.

Here's the most familiar example: If you're of northern European ancestry, you can probably digest milk, and if you're south-east Asian, you probably can't. In most mammals the gene for lactose tolerance switches off once an animal is weaned. Humans shared that fate until a mutation in the DNA of an isolated population of northern Europeans around 10,000 years ago introduced an adaptive tolerance for nutrient-rich milk. The likelihood that you tolerate milk depends on the degree to which you have northern European blood. "That, essentially, is the model - a very dramatic one," says Jim Kaput, founder of NutraGenomics, a biotechnology company.

"As humans evolved, and as our bodies interacted with foods on each of the continents, we sort of self-selected for these naturally occurring variants. And certain populations have variants that, when presented with western-type food, which is usually fatty and overprocessed and high in calories, pushes them toward disease rather than health."

Plenty of examples bear out this ill fit between certain cultures and certain diets - suggesting, if not quite proving, some interplay of genes and nutrition: Japanese who relocated to the United States after the second world war soon saw their cholesterol levels soar. The Alaskan Inuit, whose metabolism was suited to moving around all day, looking for high-fat food, were saddled with an evolutionary disadvantage when they began living in heated homes and travelling on snowmobiles. They now show high levels of obesity, diabetes and cardiovascular disease. The Masai of East Africa have developed new health problems since abandoning their traditional meat, blood and milk diet for corn and beans.

T he cradle of nutrigenomics is the cradle of humankind itself: the original migration out of Africa created widely separated subpopulations with distinct collections of gene variants. Members of each subpopulation tend to respond similarly to diet and environmental conditions. But the genetics of race is an inexact science. Since many people have ancestors from different continents data is rarely clean-cut. In other words, ethnicity is relevant to nutritional genomics but only as a starting point. Which is why the idea of sorting ourselves by race and pursuing a diet consistent with the original continental diet isn't going to be very helpful. And why, in fact, the customised diets of most people's perfect genomic future will probably not be all that different from one another.

Kaput estimates that the middle 60% of the bell curve are probably not going to need to deviate too much from the basic fruit and vegetable heavy diet recommended by the US department of agriculture.

The people who will benefit from customised nutritional packets will be the 20% at either end: those at the top who don't have to worry much about what they eat and at the bottom, who respond disastrously to conventional diets and will discover that they need to follow special diets or eat specific supplements. The problem for everyone will be figuring out where they fall on the curve of each disease profile.

How far in the future are we projecting? The staggering complexity of interactions among genes, and between genes and the environment, will be a real challenge to solve. "Eat right for your genotype" may be a decade or two - or more - down the road.

"Right now, no one in their right mind would offer genetic testing," says Dr Muin Khoury, director of the office of genomics and disease prevention at the US Centres for Disease Control.

But a handful of companies is already offering genomics profiles and nutritional supplements to early adopters. One company in America already offers a genetics testing service. Clients pay up to $1,500 (£933) for a preventive health profile.


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