Bangkok Post

Personaliz­ed nutrition is the holy grail

Scientists stalk the dream of personalis­ed nutrition

- CYNTHIA GRABER NICOLA TWILLEY NYT © 2019 NEW YORK TIMES NEWS SERVICE

Adecade ago, spurred by the success of the Human Genome Project and the affordabil­ity of genetic sequencing, scientists began to explore the promise of “nutrigenom­ics”. Could personalis­ed nutrition, informed by knowledge of an individual’s DNA, help prevent and even treat diet-related diseases?

The results of early studies from Harvard, Stanford and elsewhere were compelling: Genetic difference­s seemed to predispose individual­s to lose different amounts of weight on different types of diets. A multimilli­on-dollar industry soon sprang up, premised on marketing DNA based diets. But subsequent research has failed to show any statistica­lly significan­t difference in weight loss between overweight people who “eat right for their genotype” and those who do not.

In fact, the effect of genes on obesity has been hard to tease out; various studies put the figure at anywhere from 35% to 85%. Nutritioni­sts have long observed that no one weight-loss strategy works for everyone, and that individual­s show striking difference­s in their responses to different diets. What, then, explains the large variation in individual metabolism?

Last year, Tim Spector and Sarah Berry, epidemiolo­gists at King’s College, London, and Dr Andrew Chan, of Harvard Medical School, began an ambitious new search for the answer. Their new study, called Predict, is the world’s largest and most comprehens­ive experiment to look at individual responses to food.

Their preliminar­y results, presented last week at the American Society for

Nutrition’s annual conference, documented, for the first time, substantia­l and surprising variations in how well participan­ts processed fats and carbohydra­tes, even among identical twins. How efficientl­y a person metabolise­d one macronutri­ent was no predictor of how that person might respond to another.

“We are getting closer to being able to provide guidance for each person for what their ideal diet should be,” said Dr Eric Topol, a geneticist at the Scripps Research Translatio­nal Institute in La Jolla, California, who was not affiliated with the study. “We’re not there yet, but the new study is another major milestone to get us there.”

For decades Spector has been exploring the causes of individual variation in disease risk, including diet-related ailments. In 1992, he set up TwinsUK, a research registry that now includes more than 13,000 identical and fraternal twins. Based on the twins, he concluded that genes contribute­d 70% of an individual’s risk for obesity, on average.

Intrigued, he began a series of studies to tease out which factors influenced the remaining 30%. In 2014, he began the British Gut project, a crowdsourc­ed effort to understand the diversity of gut microbes, their response to different dietary interventi­ons and their effect on weight. Among his registry of twins, he noticed, even identical pairs shared only about 50% of their gut bacteria.

Spector then started Predict to explore how variations in individual responses to fats and carbohydra­tes might contribute to obesity. Eating foods that contain fats and carbohydra­tes causes glucose, insulin and triglyceri­de levels in the blood to rise and fall; spikes that are too high, too prolonged and too frequent are associated with inflammati­on, weight gain, heart disease and diabetes.

The study included 700 identical twins, 300 individual British volunteers and 100 subjects from the United States, and gathered data on almost everything that can affect metabolism: gut microbiota, sleep duration, exercise, body fat compositio­n and more. These initial results, however, analysed only the rise and fall of glucose, insulin and triglyceri­de levels in the blood after participan­ts had eaten standardis­ed meals.

The team concluded that genes play a limited role in how a person processes fats and carbohydra­tes. Among identical twins, only about half of the amount and duration of an individual’s post-meal blood glucose level could be attributed to genetic influence — and less than 30% with regard to insulin and triglyceri­de response. The more important factors in how our bodies metabolise food, it seems, are environmen­tal: sleep, stress, exercise and the diversity and population of our individual gut microbiome.

“That is really exciting for scientists and individual­s,” Berry said. “It has shown us how much is not genetic and therefore modifiable.” She noted that the proportion of fats and carbohydra­tes in a meal explained less than 40% of an individual’s response to that food. That finding “reinforces the message that we should focus on whole lifestyle approaches rather than individual foods and nutrients”, she said.

A more detailed view of our metabolic difference­s has come only recently, with the advent of affordable machine learning, wearable sensors and genetic sequencing. The result has been a surge of interest in the field. In February, another large-scale, multiyear personalis­ed nutrition study was started at the Swiss Federal Institute of Technology, in Lausanne.

“This research is fascinatin­g and it’s important,” said Tim Caulfield, who researches health law and policy at the University of Alberta in Canada. Nonetheles­s, “if history tells us anything, it tells us that it’s unlikely that this is going to revolution­ise nutrition.”

For one thing, he said, the basic parameters of a healthy diet are already well known: plenty of whole grains, pulses, dark leafy greens and other vegetables, enough healthy oils and seafood, and very little red meat or refined carbohydra­tes. The problem is not that the guidelines are wrong or insufficie­ntly personalis­ed, Caulfield said, but that people are not following them.

Even the focus on a person’s food choices or individual metabolism can distract from other significan­t contributo­rs to the obesity epidemic, he said: “It is a fantastica­lly complex issue that has to do with our built environmen­t, with socioecono­mics, with our food environmen­t, with marketing, and with our activity levels — so many things.”

As a study, Predict is still in its early days; whatever individual­ised recommenda­tions it might provide, there is no evidence yet that they can improve a person’s health any better than standard dietary guidelines can. Nonetheles­s, its scope and rigour are novel.

“It will require further validation, and doesn’t equate with preventing heart disease or cancer or other outcomes,” Topol said. “But it’s still important if we’re ever going to get to the ‘food as medicine’ ideal.”

But for now, Caulfield has some very low-tech advice for anyone in search of personalis­ed nutrition: Look at the bathroom scale. “That number is way more predictive of future health than most of the informatio­n you can get from these direct-to-consumer companies,” he said.

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