AI and you: Is the promise of personalized nutrition apps worth the hype?
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.”
Stacey Khoury felt more fatigued and out of breath than she was used to from just walking up the steps to her job in retail jewelry sales in Nashville, Tennessee. By the time she got home, she was more exhausted than usual, too.
"I just thought I was working too hard and needed more exercise," recalls the native Nashvillian about those days in December 2010. "All of the usual excuses you make when you're not feeling 100%."
As a professional gemologist, being hospitalized during peak holiday sales season wasn't particularly convenient. There was no way around it though when her primary care physician advised Khoury to see a blood disorder oncologist because of her disturbing blood count numbers. As part of a routine medical exam, a complete blood count screens for a variety of diseases and conditions that affect blood cells, such as anemia, infection, inflammation, bleeding disorders and cancer.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before."
While she was in the hospital, a bone marrow biopsy revealed that Khoury had acute myeloid leukemia, or AML, a high-risk blood cancer. After Khoury completed an intense first round of chemotherapy, her oncologist recommended a bone marrow transplant. The potentially curative treatment for blood-cancer patients requires them to first receive a high dose of chemotherapy. Next, an infusion of stem cells from a healthy donor's bone marrow helps form new blood cells to fight off the cancer long-term.
Each year, approximately 8,000 patients in the U.S. with AML and other blood cancers receive a bone marrow transplant from a donor, according to the Center for International Blood and Marrow Transplant Research. But Khoury wasn't so lucky. She ended up being among the estimated 40% of patients eligible for bone marrow transplants who don't receive one, usually because there's no matched donor available.
Khoury's oncologist told her about another option. She could enter a clinical trial for an investigational cell therapy called omidubicel, which is being developed by Israeli biotech company Gamida Cell. The company's cell therapy, which is still experimental, could up a new avenue of treatment for cancer patients who can't get a bone marrow transplant.
Omidubicel consists of stem cells from cord blood that have been expanded using Gamida's technology to ensure there are enough cells for a therapeutic dose. The company's technology allows the immature cord blood cells to multiply quickly in the lab. Like a bone marrow transplant, the goal of the therapy is to make sure the donor cells make their way to the bone marrow and begin producing healthy new cells — a process called engraftment.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before, so there's something very novel and exciting about that," says Ronit Simantov, Gamida Cell's chief medical officer.
Khoury and her husband Rick packed up their car and headed to the closest trial site, the Duke University School of Medicine, roughly 500 miles away. There they met with Mitchell Horowitz, a stem cell transplant specialist at Duke and principal investigator for Gamida's omidubicel study in the U.S.
He told Khoury she was a perfect candidate for the trial, and she enrolled immediately. "When you have one of two decisions, and it's either do this or you're probably not going to be around, it was a pretty easy decision to make, and I am truly thankful for that," she says.
Khoury's treatment started at the end of March 2011, and she was home by July 4 that year. She say the therapy "worked the way the doctors wanted it to work." Khoury's blood counts were rising quicker than the people who had bone marrow matches, and she was discharged from Duke earlier than other patients were.
By expanding the number of cord blood cells — which are typically too few to treat an adult — omidubicel allows doctors to use cord blood for patients who require a transplant but don't have a donor match for bone marrow.
Patients receiving omidubicel first get a blood test to determine their human leukocyte antigen, or HLA, type. This protein is found on most cells in the body and is an important regulator of the immune system. HLA typing is used to match patients to bone marrow and cord blood donors, but cord blood doesn't require as close of a match.
Like bone marrow transplants, one potential complication of omidubicel is graft-versus-host disease, when the donated bone marrow or stem cells register the recipient's body as foreign and attack the body. Depending on the severity of the response, according to the Mayo Clinic, treatment includes medication to suppress the immune system, such as steroids. In clinical trials, the occurrence of graft-versus-host disease with omidubicel was comparable with traditional bone marrow transplants.
"Transplant doctors are working on improving that," Simantov says. "A number of new therapies that specifically address graft-versus-host disease will be making some headway in the coming months and years."
Gamida released the results of the Phase 3 study in February and continues to follow Khoury and the other study patients for their long-term outcomes. The large randomized trial evaluated the safety and efficacy of omidubicel compared to standard umbilical cord blood transplants in patients with blood cancer who didn't have a suitable bone marrow donor. Around 120 patients aged 12 to 65 across the U.S., Europe and Asia were included in the trial. The study found that omidubicel resulted in faster recovery, fewer bacterial and viral infections and fewer days in the hospital.
The company plans to seek FDA approval this year. Simantov anticipates the therapy will receive FDA approval by 2022.
"Opening up cord blood transplants is very important, especially for people of diverse ethnic backgrounds," says oncologist Gary Schiller, principal investigator at the David Geffen School of Medicine at UCLA for Gamida Cell's mid- and late-stage trials. "This expansion technology makes a big difference because it makes cord blood an available option for those who do not have another donor source."
As for Khoury, who proudly celebrated the anniversary of her first transplant in April—she remains cancer free and continues to work full-time as a gemologist. When she has a little free time, she enjoys gardening, sewing, or maybe traveling to national parks like Yellowstone or the Grand Canyon with her husband Rick.
Paralyzed By Polio, This British Tea Broker Changed the Course Of Medical History Forever
In December 1958, on a vacation with his wife in Kenya, a 28-year-old British tea broker named Robin Cavendish became suddenly ill. Neither he nor his wife Diana knew it at the time, but Robin's illness would change the course of medical history forever.
Robin was rushed to a nearby hospital in Kenya where the medical staff delivered the crushing news: Robin had contracted polio, and the paralysis creeping up his body was almost certainly permanent. The doctors placed Robin on a ventilator through a tracheotomy in his neck, as the paralysis from his polio infection had rendered him unable to breathe on his own – and going off the average life expectancy at the time, they gave him only three months to live. Robin and Diana (who was pregnant at the time with their first child, Jonathan) flew back to England so he could be admitted to a hospital. They mentally prepared to wait out Robin's final days.
But Robin did something unexpected when he returned to the UK – just one of many things that would astonish doctors over the next several years: He survived. Diana gave birth to Jonathan in February 1959 and continued to visit Robin regularly in the hospital with the baby. Despite doctors warning that he would soon succumb to his illness, Robin kept living.
After a year in the hospital, Diana suggested something radical: She wanted Robin to leave the hospital and live at home in South Oxfordshire for as long as he possibly could, with her as his nurse. At the time, this suggestion was unheard of. People like Robin who depended on machinery to keep them breathing had only ever lived inside hospital walls, as the prevailing belief was that the machinery needed to keep them alive was too complicated for laypeople to operate. But Diana and Robin were up for the challenges – and the risks. Because his ventilator ran on electricity, if the house were to unexpectedly lose power, Diana would either need to restore power quickly or hand-pump air into his lungs to keep him alive.
Robin's wheelchair was not only the first of its kind; it became the model for the respiratory wheelchairs that people still use today.
In an interview as an adult, Jonathan Cavendish reflected on his parents' decision to live outside the hospital on a ventilator: "My father's mantra was quality of life," he explained. "He could have stayed in the hospital, but he didn't think that was as good of a life as he could manage. He would rather be two minutes away from death and living a full life."
After a few years of living at home, however, Robin became tired of being confined to his bed. He longed to sit outside, to visit friends, to travel – but had no way of doing so without his ventilator. So together with his friend Teddy Hall, a professor and engineer at Oxford University, the two collaborated in 1962 to create an entirely new invention: a battery-operated wheelchair prototype with a ventilator built in. With this, Robin could now venture outside the house – and soon the Cavendish family became famous for taking vacations. It was something that, by all accounts, had never been done before by someone who was ventilator-dependent. Robin and Hall also designed a van so that the wheelchair could be plugged in and powered during travel. Jonathan Cavendish later recalled a particular family vacation that nearly ended in disaster when the van broke down outside of Barcelona, Spain:
"My poor old uncle [plugged] my father's chair into the wrong socket," Cavendish later recalled, causing the electricity to short. "There was fire and smoke, and both the van and the chair ground to a halt." Johnathan, who was eight or nine at the time, his mother, and his uncle took turns hand-pumping Robin's ventilator by the roadside for the next thirty-six hours, waiting for Professor Hall to arrive in town and repair the van. Rather than being panicked, the Cavendishes managed to turn the vigil into a party. Townspeople came to greet them, bringing food and music, and a local priest even stopped by to give his blessing.
Robin had become a pioneer, showing the world that a person with severe disabilities could still have mobility, access, and a fuller quality of life than anyone had imagined. His mission, along with Hall's, then became gifting this independence to others like himself. Robin and Hall raised money – first from the Ernest Kleinwort Charitable Trust, and then from the British Department of Health – to fund more ventilator chairs, which were then manufactured by Hall's company, Littlemore Scientific Engineering, and given to fellow patients who wanted to live full lives at home. Robin and Hall used themselves as guinea pigs, testing out different models of the chairs and collaborating with scientists to create other devices for those with disabilities. One invention, called the Possum, allowed paraplegics to control things like the telephone and television set with just a nod of the head. Robin's wheelchair was not only the first of its kind; it became the model for the respiratory wheelchairs that people still use today.
Robin went on to enjoy a long and happy life with his family at their house in South Oxfordshire, surrounded by friends who would later attest to his "down-to-earth" personality, his sense of humor, and his "irresistible" charm. When he died peacefully at his home in 1994 at age 64, he was considered the world's oldest-living person who used a ventilator outside the hospital – breaking yet another barrier for what medical science thought was possible.