Those who have a friend who can eat sugary foods every day and not gain an ounce or a relative who suffers from heart disease despite avoiding saturated fat know that one-size-fits-all dietary recommendations do not reflect how differently we respond to food. But now one of the diet’s most inclusive and ambitious new studies could change that, producing insights that will allow experts to finally tailor their recommendations for different people.
Starting this spring, 13 sites across the United States will begin enrolling 10,000 people of various ages and weights to better determine the important factors involved in so-called precision nutrition. Special efforts will be made to include those who are often neglected in nutrition science: seniors over 65, people of color, rural residents, people with disabilities and sexual minorities.
During the first phase of the research, which will last for two weeks, everyone will be instructed to eat normally. In the second phase, 1,500 people will be given one of several diets with food delivered directly to their homes. And in the final phase, 500 people selected from the larger group will eat while staying at the research center for two weeks. The latter is a large number for controlled nutrition studies, which typically involve only a few dozen participants, said Holly Nicastro, who will coordinate the National Institutes of Health’s $170 million research program called Nutrition for Precision Health. Participants will be selected from NIH’s All of Us health research program, which anyone can join.
This large and diverse effort will “bring us one step closer to being able to provide more detailed dietary recommendations for individual groups,” said Sai Krupa Das, a metabolic scientist at Tufts University, one of six research centers coordinating the registry site.
How the study will work
During the study, researchers will conduct regular urine and blood tests and complete a census of each person’s gut microbiome—the trillions of organisms that live permanently in the digestive tract. Participants will wear glucose monitors to record rising and falling blood sugar levels—a marker of how well the body is processing carbohydrates and an important indicator of health. Daily behaviors such as sleep, stress and when people eat, among other factors, will also be tracked.
The new study will change our understanding of human diet because it is radically different from the way most nutrition studies are conducted, said Diana Thomas, professor of mathematics at the US Military Academy at West Point, who was involved in the research. Nutritional scientists generally examine a single food item in a homogeneous population, asking, say, whether blueberries reduce the risk of cardiovascular disease in Americans (the answer to that is still unclear). In this study, we don’t start with a hypothesis, he says, but “we ask, what factors are involved?”
The goal is to tease out the many variables that impact dietary responses and develop algorithms that predict them, allowing nutritionists to offer nutritional advice to others with similar characteristics.
Offering more targeted recommendations is critical to improving public health, Das said. The current approach has led many people to reject expert nutritional advice, either because the advice seems to change frequently (classic: eggs are bad; eggs are good) or because they try the recommended diet and find it doesn’t work for them. “Precision nutrition will allow us to do better than one-size-fits-all, go-to-eat-in-the-Mediterranean diet advice. Instead, we would say, ‘If you have a certain ethnicity, characteristics, physical response to food, this diet may be more appropriate.’ That is the step we are getting closer to,” he said.
Das cautions that new advice derived from research will not reach the individual level, which is why experts prefer the term precision nutrition to another widely used term, personal nutrition.
The study will focus on nutrition for optimal health rather than weight loss, but the two go hand in hand, Das said. “We’re not providing a calorie-restricted diet, but I think the response in terms of trying to optimize metabolism will be helpful for weight management as well.”
Genes vs microbiome
Decades of research have already yielded clues about the elements that make up overall health.
One of them is genetics. The field was previously called nutrigenomics, but it fell out of favor when it became clear that genes play a less prominent role in how the body responds to food than originally thought, says José Ordovás, director of nutrition and genomics at Tufts University.
In a small number of cases, scientists have tied specific genes to direct health effects. The CYP1A2 gene, for example, is almost single-handedly responsible for determining how quickly the enzyme metabolizes caffeine in the liver. Genetic variation determines whether an afternoon cup of joe keeps someone up all night or still allows them to get a good night’s sleep. It also affects whether coffee will help someone exercise at a higher intensity, such as riding a bike faster.
“Genetics is involved, but it will not give us a predictive equation to individualize the proposal, because so many other factors are involved,” says Ordovás. Since many of those factors, especially behavior, are easier to change than our genes, understanding them should lead to more effective approaches to improving health, he said.
Hundreds of studies have shown that the microbiome—the bacteria, fungi, parasites, and viruses that live in the gut—is a critical factor in how the body processes food. Consuming artificial sweeteners, for example, alters the composition and function of the microbiome in ways that increase glucose intolerance in healthy people. And certain gut microbes persist in obese mice after dieting, which predisposes them—and perhaps us—to weight regain.
Much remains to be learned about the microbiome, including its optimal composition, how microbes work synergistically and how lifestyle affects this community, says Eran Elinav, head of systems immunology at Israel’s Weizmann Institute of Science and a prolific microbiome researcher.
How lifestyle affects the way we process food
One of the trickiest things about figuring out the perfect diet for everyone is the complex interplay between our genome, microbiome, and lifestyle factors—the latter of which scientists call the exposome.
One of the lifestyle factors is when we eat dinner, says Elinav. His lab determined that the gut microbiome obeys a circadian rhythm, with the composition of the microbiota predictably changing in number and function over a 24-hour period. They do this by responding to cues from sleeping and eating behavior.
“When we disrupt our sleep-wake patterns with shift work or jet lag,” says Elinav, “one of the first things that happens is that this disrupts the daily activity of microbes.” The increased rates of obesity, type 2 diabetes, and cancer associated with people whose sleep and eating schedules are chronically disrupted stem from these changes in the microbiome, a study in mice suggests.
Poor sleep, along with intense stress, also disrupts metabolism and has other negative health effects even in people who eat a healthy diet, says Tufts’ Das.
NIH’s precision nutrition research will be the most comprehensive effort to use genes, microbiota, and expososomes to understand and predict nutritional responses to food, but it won’t be the first. Some previous studies have paved the way.
An effort, led by the Elinav laboratory and published in the journal cell in 2015, involved feeding the same food to 800 people and constantly monitoring their blood glucose levels. The week-long study revealed that glucose responses among participants differed significantly after each meal. Researchers note that the composition of their microbiome plays an important role in determining that response, but other factors are inevitably involved.
A few years later a large study in the United Kingdom sought to expand knowledge about the variables at play. Called the Personalized Response to Diet Composition Trial, or PREDICT, the research involved a thousand adults—including several genetically identical twins—whose gut microbiota, blood fats, postprandial glucose levels, inflammation and other factors were monitored for two weeks. Tracking blood glucose throughout the day is again an important element, says Tufts’ Ordovás, one of the co-authors. Such continuous monitoring allows researchers to measure the effects of specific foods.
Here, too, wide variations emerged indicating that participants’ bodies processed the same nutrients differently. Genetic factors have been shown to have a modest effect, but the findings show how complex the digestive system is. Certain gut microbes—incl Prevotella copri and Blastocystis—more important than genes for processing some foods—but both still account for only a fraction of the overall difference.
The goal of upcoming NIH research is to improve understanding of the factors that contribute to those differences. The hope is that this will allow people to adjust their lifestyle and diet and perhaps their gut microbes to improve their body’s response to various nutrients. (Whether manipulating the microbiota, such as through dietary changes, has lasting effects remains unclear.)
For now, Das says the best nutritional advice he and others offer sticks to the basics: fill your plate with fiber-rich vegetables and fruits and avoid highly processed foods in favor of whole foods.
“In the next five to 10 years there will be a big change in the way we look at diet,” Thomas West Point predicts. “When the results from the NIH study start coming in, we’ll know a lot more.”
