A decade 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 difficult to tease out; various studies put the figure at anywhere from 35 per cent to 85 per cent. 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 this month 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."
Based on the twins, he concluded that genes contributed 70 per cent of an individual's risk for obesity, on average
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 per cent of an individual’s risk for obesity, on average.
Diversity of gut microbes
Intrigued, he began a series of studies to tease out which factors influenced the remaining 30 per cent. In 2014, he began the British Gut project, a crowd-sourced 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 per cent 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 more important factors in how our bodies metabolise food, it seems, are environmental
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 per cent 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 per cent 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.
The full data set will take Spector and his extended team of colleagues – some 40 scientists around the world – years to analyse, even with the help of machine learning. And they have already begun follow-up studies to tease out the complex relationships among factors.
But it was already possible to glean individual insights, he said. After eating potato chips, one subject repeatedly experienced a triglyceride peak six times higher than that of an identical twin. That degree of awareness could help steer the chip-sensitive twin toward a lower-fat snack, Spector said.
“We are omnivores and we do need a diverse diet,” he said. “But if you can just swap some foods around so that you have exactly the same calories and enjoyment, but a lower peak either in glucose or in lipids, then you’re going to put on less weight and be healthier long term.”
I think the one-size-fits-all nutrition guideline is antiquated
Jennie Brand-Miller, a professor of human nutrition at the University of Sydney in Australia, who was not involved with Predict, said that individualised nutrition advice, rather than standard dietary guidelines based on population-wide averages, could significantly improve public health. "I think the one-size-fits-all nutrition guideline is antiquated," Brand-Miller said. She noted that one in three people have a poor metabolic response to sugar; identifying those individuals, and then teaching them how to avoid spikes in blood glucose, could reduce their odds of later developing diabetes by as much as 40 per cent.
The standard nutrition guidelines are built on data from questionnaires that ask people how frequently they ate certain foods in the past year. That approach provides useful data about overall trends, but it also is flawed: respondents are notoriously bad at recalling their food choices, and the averaged data cannot offer personalised guidance.
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 rigor 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.”
Participating in the study can be gruelling. Subjects are first put through an extensive battery of tests, including hourly blood draws and scans of their body fat and bone mass, in a hospital setting. Then, for two weeks, they must consume a series of set “meals” – a selection of muffins containing different combinations of fat, carbohydrate and protein, along with fibre bars, glucose drinks and protein shakes. Any other food or beverage consumed must be weighed and logged. Each participant wears a continuous glucose monitor and an accelerometer to measure activity levels and sleep, and provides samples of saliva, urine, faeces and blood – everything but tears.
That is only the start of Spector’s ambitions. He has already started Predict Plus, with some of the “super-loggers” from the first study, and is recruiting participants for an expanded version of the original study, called Predict Two. The research is supported by the Wellcome Trust and the United Kingdom’s National Institute for Health Research.
With entrepreneurs, Spector also has started a for-profit company, Zoe, with the hope of creating an app that would offer users individualised nutrition advice about how to eat and, ultimately, how their bodies might respond to foods they have not yet tried.
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. – New York Times