The National Institute for Health (NIH)’s $180 million study to understand how our bodies respond to food and whether a personalised diet can help improve health and prevent chronic disease.
In the large-scale $180 million (€168 million) four-year study, Nutrition for Precision Health (NPH) will analyse the relationship between personalisation in diet and its impact on health and chronic disease prevention. Created by the NIH and powered by the All of Us Research Programme, the NPH began in April 2023 after the precision nutrition study’s design was approved earlier in 2023.
“We are going towards precision medicine, but we must do precision behaviours or precision lifestyles regarding nutrition and physical activity,” says Dr Eric Ravussin, associate executive director for clinical science at Pennington Biomedical in Baton Rouge, US.
Relationship between personalisation in diets and health
“There is no question that nutrition is at the epicentre of human health and disease,” says Ravussin. Nutrition and physical activity are two lifestyle behaviours associated with health. We are now facing a decrease in the population’s lifespan, mainly related to these lifestyle behaviours, Ravussin notes.
Discussions with the National Institute of Health (NIH) over the past ten years have pointed towards adopting a more customised diet rather than a one-size-fits-all one, Ravussin says.
In today’s society, Ravussin continues, “you have the diet of the year, [which] is one-size-fits-all”. Recommendations concerning these diets are largely unfollowed, and when they are, “they are failing a large segment of the population”.
Personalisation is growing as a potential solution to move away from generic dietary guidance and provide individualised nutrition advice.
The precision nutrition study
NIH had a Request for Application (RFA) to launch a large-scale study called NPH. Six clinical sites were chosen, with awards granted in December 2021 and January 2022. After forming a consortium, the first task was to design a study all six sites could agree on and submit this to the Institutional Review Board (IRB) and the Data Safety Monitoring Board (DSMB).
As the NPH study is ancillary to the All of US programme, the researchers will already have access to data on the participants’ health, anthropometrics and genetics because they provide access to their electronic health records (EHRs). The researchers will study individual factors, including genetics, metabolism, physiology, the microbiome, behaviours, and the built and contextual environment in the NPH, which they note are all essential underlying mechanisms of the variability in response to diet.
The NPH study contains three modules:
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Module 1: Knowing dietary habits
Using a discovery science approach and cross-sectional data, the first module has approximately 10,000 enrolled study participants and lasts about two weeks. The researchers investigate the participants’ dietary habits, where they live, social-economical status, degree of education, and significant behaviours.
During these two weeks, there are ten days of Continuous Glucose Monitoring (CGM), where the researchers will measure participants’ glucose profiles before undertaking a liquid meal tolerance test. The researchers will collect fasting blood over four hours to measure relevant metrics, including omics, proteomics and lipidomics.
At the end of the two weeks, researchers will collect stools, saliva and other biosamples, which are analysed for different omics. The goal is to put all the collected data into a database, where machine learning will build an algorithm to see the response to this single meal and its variability.
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Module 2: Making dietary changes
The second module is an intervention as part of a crossover randomised study, analysing 1,500 of the 10,000 people’s diets. These participants then receive three different diets for two weeks. The researchers repeat specific measurements, particularly the response to the liquid meal tolerance test and breakfast.
These 1,500 people are randomised to these three diets for two weeks each, separated by a washout period of two weeks to one month. The 1,500 participants consume the food given to them at home and collect their diet every three days.
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Module 3: Research to confirm diet recommendation
“In free-living conditions, some people will eat a lot of other things and will not eat all of their diets,” says Ravussin. As a result, the study moves to its third module, “creating a very controlled study”. Module three involves 500 patients across the six clinical centres. They are in a hospital-like system, a general clinical research centre, for three periods of two weeks.
Personalisation and disease management
While ongoing investigations into the connection between diet, health and disease prevention are present, these have been primarily epidemiological studies, Ravussin says. The UK’s Biobank and the US’s NHANES are examples of such studies.
While these are extensive studies, Ravussin says they mainly involve questionnaires and have limited biological data. The NPH study, however, is “much more controlled, biologically and environmentally geared”, Ravussin says. As many factors are being measured, the researchers can gather more understanding to determine cause and effect regarding diet based on conditions and markers, genetic background, and geographic location, such as whether the participant lives in urban or rural areas.
“With artificial intelligence and machine learning, we can design algorithms to predict who will benefit from such diet, from such physical activity versus those who do not,” says Ravussin. “This is what it is all about with precision medicine,” adds Ravussin.
Research studies have sought to understand how personalisation in diet and exercise can affect overall health. The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study in the UK explores diet. The Molecular Transducers of Physical Activity Consortium (MORTPAC) in the US examines the role of physical activity on health.
True personalisation?
Some may question whether diets can ever be genuinely personalised or if they undergo more of a customisation lens. “There are always limits,” says Ravussin. However, as these participants are part of the All of Us programme, the researchers have access to genome sequencing results.
Researchers will therefore have information on the participants’ medical history. They will also measure some parts of their metabolism and some physiology and will know about the microbiota because they will collect three stool samples.
“We will know the variability in the response to this meal,” says Ravussin. “We can therefore have algorithms predicting the response in people that we have not studied before,” Ravussin adds.
Ultimately, however, the researchers will categorise people into groups. “It is a little bit of an illusion to say it is going to be personalised, but it is going to be very specific to a group of people,” says Ravussin.
Editorial notes
Source: Interview with Dr Eric Ravussin, associate executive director for clinical science at Pennington Biomedical in Baton Rouge, US.
