Personalized nutrition apps could provide valuable data to people trying to eat healthier, though more research must be done to show effectiveness.
As a type 2 diabetic, Michael Snyder has long been interested in how blood sugar levels vary from one person to another in response to the same food, and whether a more personalized approach to nutrition could help tackle the rapidly cascading levels of diabetes and obesity in much of the western world.
Eight years ago, Snyder, who directs the Center for Genomics and Personalized Medicine at Stanford University, decided to put his theories to the test. In the 2000s continuous glucose monitoring, or CGM, had begun to revolutionize the lives of diabetics, both type 1 and type 2. Using spherical sensors which sit on the upper arm or abdomen – with tiny wires that pierce the skin – the technology allowed patients to gain real-time updates on their blood sugar levels, transmitted directly to their phone.
It gave Snyder an idea for his research at Stanford. Applying the same technology to a group of apparently healthy people, and looking for ‘spikes’ or sudden surges in blood sugar known as hyperglycemia, could provide a means of observing how their bodies reacted to an array of foods.
“We discovered that different foods spike people differently,” he says. “Some people spike to pasta, others to bread, others to bananas, and so on. It’s very personalized and our feeling was that building programs around these devices could be extremely powerful for better managing people’s glucose.”
Unbeknown to Snyder at the time, thousands of miles away, a group of Israeli scientists at the Weizmann Institute of Science were doing exactly the same experiments. In 2015, they published a landmark paper which used CGM to track the blood sugar levels of 800 people over several days, showing that the biological response to identical foods can vary wildly. Like Snyder, they theorized that giving people a greater understanding of their own glucose responses, so they spend more time in the normal range, may reduce the prevalence of type 2 diabetes.
The commercial potential of such apps is clear, but the underlying science continues to generate intriguing findings.
“At the moment 33 percent of the U.S. population is pre-diabetic, and 70 percent of those pre-diabetics will become diabetic,” says Snyder. “Those numbers are going up, so it’s pretty clear we need to do something about it.”
Fast forward to 2022,and both teams have converted their ideas into subscription-based dietary apps which use artificial intelligence to offer data-informed nutritional and lifestyle recommendations. Snyder’s spinoff, January AI, combines CGM information with heart rate, sleep, and activity data to advise on foods to avoid and the best times to exercise. DayTwo–a start-up which utilizes the findings of Weizmann Institute of Science–obtains microbiome information by sequencing stool samples, and combines this with blood glucose data to rate ‘good’ and ‘bad’ foods for a particular person.
“CGMs can be used to devise personalized diets,” says Eran Elinav, an immunology professor and microbiota researcher at the Weizmann Institute of Science in addition to serving as a scientific consultant for DayTwo. “However, this process can be cumbersome. Therefore, in our lab we created an algorithm, based on data acquired from a big cohort of people, which can accurately predict post-meal glucose responses on a personal basis.”
The commercial potential of such apps is clear. DayTwo, who market their product to corporate employers and health insurers rather than individual consumers, recently raised $37 million in funding. But the underlying science continues to generate intriguing findings.
Last year, Elinav and colleagues published a study on 225 individuals with pre-diabetes which found that they achieved better blood sugar control when they followed a personalized diet based on DayTwo’s recommendations, compared to a Mediterranean diet. The journal Cell just released a new paper from Snyder’s group which shows that different types of fibre benefit people in different ways.
“The idea is you hear different fibres are good for you,” says Snyder. “But if you look at fibres they’re all over the map—it’s like saying all animals are the same. The responses are very individual. For a lot of people [a type of fibre called] arabinoxylan clearly reduced cholesterol while the fibre inulin had no effect. But in some people, it was the complete opposite.”
Eight years ago, Stanford's Michael Snyder began studying how continuous glucose monitors could be used by patients to gain real-time updates on their blood sugar levels, transmitted directly to their phone.
The Snyder Lab, Stanford Medicine
Because of studies like these, interest in precision nutrition approaches has exploded in recent years. In January, the National Institutes of Health announced that they are spending $170 million on a five year, multi-center initiative which aims to develop algorithms based on a whole range of data sources from blood sugar to sleep, exercise, stress, microbiome and even genomic information which can help predict which diets are most suitable for a particular individual.
“There's so many different factors which influence what you put into your mouth but also what happens to different types of nutrients and how that ultimately affects your health, which means you can’t have a one-size-fits-all set of nutritional guidelines for everyone,” says Bruce Y. Lee, professor of health policy and management at the City University of New York Graduate School of Public Health.
With the falling costs of genomic sequencing, other precision nutrition clinical trials are choosing to look at whether our genomes alone can yield key information about what our diets should look like, an emerging field of research known as nutrigenomics.
The ASPIRE-DNA clinical trial at Imperial College London is aiming to see whether particular genetic variants can be used to classify individuals into two groups, those who are more glucose sensitive to fat and those who are more sensitive to carbohydrates. By following a tailored diet based on these sensitivities, the trial aims to see whether it can prevent people with pre-diabetes from developing the disease.
But while much hope is riding on these trials, even precision nutrition advocates caution that the field remains in the very earliest of stages. Lars-Oliver Klotz, professor of nutrigenomics at Friedrich-Schiller-University in Jena, Germany, says that while the overall goal is to identify means of avoiding nutrition-related diseases, genomic data alone is unlikely to be sufficient to prevent obesity and type 2 diabetes.
“Genome data is rather simple to acquire these days as sequencing techniques have dramatically advanced in recent years,” he says. “However, the predictive value of just genome sequencing is too low in the case of obesity and prediabetes.”
Others say that while genomic data can yield useful information in terms of how different people metabolize different types of fat and specific nutrients such as B vitamins, there is a need for more research before it can be utilized in an algorithm for making dietary recommendations.
“I think it’s a little early,” says Eileen Gibney, a professor at University College Dublin. “We’ve identified a limited number of gene-nutrient interactions so far, but we need more randomized control trials of people with different genetic profiles on the same diet, to see whether they respond differently, and if that can be explained by their genetic differences.”
Some start-ups have already come unstuck for promising too much, or pushing recommendations which are not based on scientifically rigorous trials. The world of precision nutrition apps was dubbed a ‘Wild West’ by some commentators after the founders of uBiome – a start-up which offered nutritional recommendations based on information obtained from sequencing stool samples –were charged with fraud last year. The weight-loss app Noom, which was valued at $3.7 billion in May 2021, has been criticized on Twitter by a number of users who claimed that its recommendations have led to them developed eating disorders.
With precision nutrition apps marketing their technology at healthy individuals, question marks have also been raised about the value which can be gained through non-diabetics monitoring their blood sugar through CGM. While some small studies have found that wearing a CGM can make overweight or obese individuals more motivated to exercise, there is still a lack of conclusive evidence showing that this translates to improved health.
However, independent researchers remain intrigued by the technology, and say that the wealth of data generated through such apps could be used to help further stratify the different types of people who become at risk of developing type 2 diabetes.
“CGM not only enables a longer sampling time for capturing glucose levels, but will also capture lifestyle factors,” says Robert Wagner, a diabetes researcher at University Hospital Düsseldorf. “It is probable that it can be used to identify many clusters of prediabetic metabolism and predict the risk of diabetes and its complications, but maybe also specific cardiometabolic risk constellations. However, we still don’t know which forms of diabetes can be prevented by such approaches and how feasible and long-lasting such self-feedback dietary modifications are.”
Snyder himself has now been wearing a CGM for eight years, and he credits the insights it provides with helping him to manage his own diabetes. “My CGM still gives me novel insights into what foods and behaviors affect my glucose levels,” he says.
He is now looking to run clinical trials with his group at Stanford to see whether following a precision nutrition approach based on CGM and microbiome data, combined with other health information, can be used to reverse signs of pre-diabetes. If it proves successful, January AI may look to incorporate microbiome data in future.
“Ultimately, what I want to do is be able take people’s poop samples, maybe a blood draw, and say, ‘Alright, based on these parameters, this is what I think is going to spike you,’ and then have a CGM to test that out,” he says. “Getting very predictive about this, so right from the get go, you can have people better manage their health and then use the glucose monitor to help follow that.”
The Svalbard Global Seed Vault preserves more than one million of the world's seeds deep inside Platäfjellet Mountain.
"Before, we trusted the permafrost. We do not trust the permafrost anymore."
Art installations on the building's rooftop and front façade glimmer like diamonds in the polar night, but it is what lies buried deep inside the frozen rock, 475 feet from the building's entrance, that is most precious. Here, in the Svalbard Global Seed Vault, are backup copies of more than a million of the world's agricultural seeds.
Inside the vault, seed boxes from many gene banks and many countries. "The seeds don't know national boundaries," says Kent Nnadozie, the UN's Secretary of the International Treaty on Plant Genetic Resources for Food and Agriculture.
(Photo credit: Svalbard Global Seed Vault/Riccardo Gangale)
The Svalbard vault -- which has been called the Doomsday Vault, or a Noah's Ark for seeds -- preserves the genetic materials of more than 6000 crop species and their wild relatives, including many of the varieties within those species. Svalbard's collection represents all the traits that will enable the plants that feed the world to adapt – with the help of farmers and plant breeders – to rapidly changing climactic conditions, including rising temperatures, more intense drought, and increasing soil salinity. "We save these seeds because we want to ensure food security for future generations," says Grethe Helene Evjen, Senior Advisor at the Norwegian Ministry of Agriculture and Food .
A recent study in the journal Nature predicted that global warming could cause catastrophic losses of biodiversity in regions across the globe throughout this century. Yet global warming also threatens the permafrost that surrounds the seed vault, the very thing that was once considered a failsafe means of keeping these seeds frozen and safeguarding the diversity of our crops. In fact, record temperatures in Svalbard a few years ago – and a significant breach of water into the access tunnel to the vault -- prompted the Norwegian government to invest $20 million euros on improvements at the facility to further secure the genetic resources locked inside. The hope: that technology can work in concert with nature's freezer to keep the world's seeds viable.
"Before, we trusted the permafrost," says Hege Njaa Aschim, a spokesperson for Statsbygg, the government agency that recently completed the upgrades at the seed vault. "We do not trust the permafrost anymore."
The Apex of the Global Conservation System
More than 1700 genebanks around the globe preserve the diverse seed varieties from their regions. They range from small community seed banks in developing countries, where small farmers save and trade their seeds with growers in nearby villages, to specialized university collections, to national and international genetic resource repositories. But many of these facilities are vulnerable to war, natural disasters, or even lack of funding.
"If anything should happen to the resources in a regular genebank, Svalbard is the backup – it's essentially the apex of the global conservation system," says Kent Nnadozie, Secretary of the International Treaty on Plant Genetic Resources for Food and Agriculture at the United Nations, who likens the Global Vault to the Central Reserve Bank. "You have regular banks that do active trading, but the Central Bank is the final reserve where the banks store their gold deposits."
Similarly, farmers deposit their seeds in regional genebanks, and also look to these banks for new varieties to help their crops adapt to, say, increasing temperatures, or resist intrusive pests. Regional banks, in turn, store duplicates from their collections at Svalbard. These seeds remain the sovereign property of the country or institution depositing them; only they can "make a withdrawal."
The Global Vault has already proven invaluable: The International Centre for Agricultural Research in the Dry Areas (ICARDA), formerly located outside of Aleppo, Syria, held more than 140,000 seed samples, including plants that were extinct in their natural habitats, before the Syrian Crisis in 2012. Fortunately, they had managed to back up most of their seed samples at Svalbard before they were forced to relocate to Lebanon and Morocco. In 2017, ICARDA became the first – and only – organization to withdraw their stored seeds. They have now regenerated almost all of the samples at their new locations and recently redeposited new seeds for safekeeping at Svalbard.
Rapid Global Warming Threatens Permafrost
The Global Vault, a joint venture between the Norwegian government, the Crop Trust and the Nordic Genetic Resource Centre (NordGen) that started operating in 2008, was sited in Svalbard in part because of its remote yet accessible location: Svalbard is the northernmost inhabited spot on Earth with an airport. But experts also thought it a failsafe choice for long-term seed storage because its permafrost would offer natural freezing – even if cooling systems were to fail. No one imagined that the permafrost could fail.
"We've had record temperatures in the region recently, and there are a lot of signs that global warming is happening faster at the extreme latitudes," says Geoff Hawtin, a world-renowned authority in plant conservation, who is the founding director of -- and now advisor to -- the Crop Trust. "Svalbard is still arguably one of the safest places for the seeds from a temperature point of view, but it's actually not going to be as cold as we thought 20 years ago."
A recent report by the Norwegian Centre for Climate Services predicted that Svalbard could become 50 degrees Fahrenheit warmer by the year 2100. And data from the Norwegian government's environmental monitoring system in Svalbard shows that the permafrost is already thawing: The "active layer," that is, the layer of surface soil that seasonally thaws, has become 25-30 cm thicker since 1998.
Among the 35 depositors were several bringing their seeds to Svalbard for the first time, including the Cherokee Nation, which deposited nine heirloom seed varieties that predate European colonization.
Though the permafrost surrounding the seed vault chambers, which are situated well below the active layer, is still intact, the permafrost around the access tunnel never re-established as expected after construction of the Global Vault twelve years ago. As a result, when Svalbard saw record high temperatures and unprecedented rainfall in 2016, about 164 feet of rainwater and snowmelt leaked into the tunnel, turning it into a skating rink and spurring authorities to take what they called a "better safe than sorry approach." They invested in major upgrades to the facility. "The seeds in the vault were never threatened," says Aschim, "but technology has become more important at Svalbard."
Technology Gives Nature a Boost
For now, the permafrost deep inside the mountain still keeps the temperature in the vault down to about -25°F. The cooling systems then give nature a mechanical boost to keep the seed vault chilled even further, to about -64°F, the optimal temperature for conserving seeds. In addition to upgrading to a more effective and sustainable cooling system that runs on CO2, the Norwegian government added backup generators, removed heat-generating electrical equipment from inside the facility to an outside building, installed a thick, watertight door to the vault, and replaced the corrugated steel access tunnel with a cement tunnel that uses the same waterproofing technology as the North Sea oil platforms.
To re-establish the permafrost around the tunnel, they layered cooling pipes with frozen soil around the concrete tunnel, covered the frozen soil with a cooling mat, and topped the cooling mat with the original permafrost soil. They also added drainage ditches on the mountainside to divert meltwater away from the tunnel as the climate gets warmer and wetter.
New Deposits to the Global Vault
The day before COVID-19 arrived in Norway, on February 25th, Prime Minister Erna Solberg hosted the biggest seed-depositing event in the vault's history in honor of the new and improved vault. As snow fell on Svalbard, depositors from almost every continent traveled the windy road from Longyearbyen up Platåfjellet Mountain and braved frigid -8°F weather to celebrate the massive technical upgrades to the facility – and to hand over their seeds.
Among the 35 depositors were several bringing their seeds to Svalbard for the first time, including the Cherokee Nation, which deposited nine heirloom seed varieties that predate European colonization, and Israel's University of Haifa, whose deposit included multiple genotypes of wild emmer wheat, an ancient relative of the modern domesticated crop. The storage boxes carried ceremoniously over the threshold that day contained more than 65,000 new seed samples, bringing the total to more than a million, and almost filling the first of three seed chambers in the vault. (The Global Vault can store up to 4.5 million seed samples.)
"Svalbard's samples contain all the possibilities, all the options for the future of our agricultural crops – it's how crops are going to adapt," says Cary Fowler, former executive director of the Crop Trust, who was instrumental in establishing the Global Vault. "If our crops don't adapt to climate change, then neither will we." Dr. Fowler says he is confident that with the recent improvements in the vault, the seeds are going to remain viable for a very long time.
"It's sometimes tempting to get distracted by the romanticism of a seed vault inside a mountain near the North Pole – it's a little bit James Bondish," muses Dr. Fowler. "But the reality is we've essentially put an end to the extinction of more than a million samples of biodiversity forever."
