Can fasting help you live to 100?
Clip source: Can fasting help you live to 100?
https://www.economist.com/1843/2024/06/07/can-fasting-help-you-live-to-100
On a warm July evening in 2022, the residents of Varapodio, a small town in the southern Italian province of Calabria, came together for a celebration.A marching band played classical tunes in front of the church, which was adorned with hundreds of multi-coloured fairy lights. A priest stood solemnly holding a silver chalice of holy water as the mayor cheerfully shook hands with some of the guests – around 100 people of all ages, many of whom were dressed in their Sunday best.
The party had been thrown in honour of Valter Longo, an Italian scientist known for his research into the benefits of fasting. Longo lives between Milan, where he works at the Institute of Molecular Oncology (IFOM), and Los Angeles, where he is the director of the Longevity Institute at the University of Southern California (USC).A slim, suave 56-year-old with messy brown hair, he wore jeans and a black shirt with rolled-up sleeves. Smiling, Longo cut a festive ribbon with scissors given to him by the mayor; the priest sprinkled him with holy water as onlookers applauded. Afterwards everyone moved slowly towards the town square to hear Longo tell them the secret of how to prolong their lives.
Longo had come to Calabria, his family’s home region – his parents were from Molochio, a town near Varapodio – to find subjects for a study he was conducting about the effects of fasting on human lifespans. Italians have historically enjoyed higher life expectancies than people in many other rich Western nations. The average Italian can hope to live to 83: two years longer than the average Briton and six years longer than the average American (and only two years less than the average Japanese). Molochio itself is famous in Italy for producing centenarians: over the past two decades it has been home to three times more than the Italian national average.
Longo cut a festive ribbon with scissors given to him by the mayor; the priest sprinkled him with holy water as onlookers applauded. Afterwards everyone moved slowly towards the town square to hear Longo tell them the secret of how to prolong their lives
But Longo, who sat poised and alert behind a long table with the town’s officials at the centre of the square, reminded the crowd that despite living in "a place of extraordinary longevity" they were not guaranteed long lives. Today, nearly 8% of adults in Italy’s southern regions suffer from diabetes (the majority of cases are type 2, which is linked to obesity). A third of children and teenagers in Calabria are overweight or obese – one of the highest regional figures across Italy. According to a 2022 report from Save the Children, an NGO, Calabrians are expected to remain in good health only until their mid-50s (other Italians usually get at least another decade of well-being; the Swedes, nearly 20 years more). One reason for this is thought to be a rise in the consumption of highly processed foods, especially among the hard-up.
Longo has devoted his career to trying to prove that fasting can extend people’s lives and improve their health. Research from fellow scientists has shown that going without food in the short-term can activate stem cells (the only cells in the body that can make different cell types) and trigger autophagy, a process by which ordinary cells recycle their damaged parts and rejuvenate.Longo believes these processes can be harnessed to slow down ageing and help treat diseases such as cancer, diabetes and Alzheimer’s.
Fame has come Longo’s way: Hollywood parties, testimonials from celebrities like Paris Hilton, Eva Longoria and Jennifer Aniston, and even an invitation from the pope to hold a conference at the Vatican. So has scepticism from other scientists
He has translated his own research into four self-help books – one of which outlines his controversial ideas on how fasting can help prevent and beat cancer – and a business called L-Nutra. The company’s flagship product, which is used by Longo’s patients as well as sold to the general public, is the ProLon 5-Day Diet: a set of pre-packaged meals that trick the body into thinking it is fasting while still providing a scant number of calories. (This sort of plan is known as a fasting-mimicking diet, or FMD.) Fame has come Longo’s way: Hollywood parties, testimonials from celebrities like Paris Hilton, Eva Longoria and Jennifer Aniston, and even an invitation from the pope to hold a conference at the Vatican. So has scepticism from other scientists, who think Longo is moving too fast in a nascent field, and has too many conflicts of interest.
For his latest study, Longo sought to measure how what he called "established markers for ageing" (a concept whose existence is still hotly debated by many scientists), such as total cholesterol, and other disease-risk factors were affected by an FMD. In the process, he hoped to counter a common criticism of his work – namely, that his research did not draw from large enough pools of participants – by recruiting over 500 volunteers in Varapodio and nearby towns. He was looking for candidates between the ages of 30 and 65, with underlying medical conditions (such as obesity or high cholesterol), to commit to his study for six months. The volunteers would be subdivided into three groups: one that would use an FMD for five days twice during the trial, otherwise following their usual diet; one that would alternate between an FMD and a so-called "longevity diet" – a mostly vegan regimen (similar to the so-called "Mediterranean diet") promoted by Longo’s four clinics in Italy and America; and a control group, which would not fast at all and maintain their regular eating habits.
About 25 people who met the study criteria signed up on the night of the celebration. Longo’s uncle Salvatore, who lived in Molochio, explained to me that locals, though aware of their own reputation for longevity, were generally sceptical of doctors studying them. At a nearby café, a clique of older men were looking suspiciously at Longo. "All bullshit," one of them told me. "We don’t need these doctors to live longer."
But others wanted to know more. As the 18th-century church glowed in the evening light,Longo stood patiently for selfies and listened as people sought his advice on high cholesterol, hypertension and strokes.He responded to each person in a refrain: the solution to their medical woes might well be fasting.
The idea that abstaining from food might have therapeutic value dates back to the Ancient Greeks. Hippocrates thought it could alleviate the symptoms of epilepsy; Pythagoras fasted for 40 days before his exams to enhance his lucidity and strength. Galen, a Greco-Roman doctor, thought that eating less would make old people healthier – advice also dished out in 11th-century Persia by Avicenna, a polymath considered to be one of the fathers of modern medicine.
By the early 20th century, scientists had developed a stronger understanding of the links between eating habits, human physiology and disease; those living in industrialised societies were also interested in the connection between one’s health and productivity at work. There was a surge of both popular books and academic research exploring the medical applications of fasting – some of which were controversial. Between 1915 and 1922 (when insulin was introduced), the American physicians Frederick Allen and Elliott Joslin prescribed intense, protracted fasting to relieve the symptoms of their diabetic patients; of the 44 people involved in their study in 1915, nearly half died during or shortly after the therapy. In the 1940s Ancel Keys, an American physiologist famous for extolling the virtues of a "Mediterranean diet", starved 32 fit men for six months to study the effects of fasting on the human body, only to conclude that starvation had a detrimental impact on the participants’ physical, social and psychological well-being.
Other human experiments had more positive outcomes. In 1965Angus Barbieri, a 27-year-old Scottish man weighing over 200kg, fasted for over a year under medical supervision. Subsisting solely off zero-calorie drinks, vitamins and electrolytes, he lost more than half of his body weight – seemingly showing that the more fat you have in your body, the longer you can survive in starvation mode. (Barbieri holds the Guinness World Record for the longest fast without solid food.)
This fad for fasting – and the perception that it is a clear path to weight-loss and "wellness" – creates opportunities for charlatans
The field of study continued to be dismissed for several decades; few clinical trials on fasting were conducted, and credible scientific publications were scarce. By the 1990s some researchers shifted their focus to the benefits of short-term fasting.OhsumiYoshinori, a Japanese cell biologist, discovered the mechanisms behind autophagy, which short-term fasting promotes (in 2016 he won a Nobel prize for his work). Over the past 20 years, Satchidananda Panda, an American biologist, and Mark Mattson, an American neuroscientist, have each studied how time-restricted eating (which involves consuming food during only a brief span of the day) could improve metabolic conditions, such as diabetes.It didn’t take long for the general public to embrace short-term fasting. Millions of people around the world have now experimented with the 5:2 diet (reducing one’s calorie intake for two days a week) or intermittent fasting (switching between periods of fasting and periods of unrestricted eating). A survey in 2022 found that one in ten Americans had tried an intermittent-fasting diet at some point in the previous year.
This fad for fasting – and the perception that it is a clear path to weight-loss and "wellness" – creates opportunities for charlatans. Online gurus, health blogs and influencers praise the purported benefits of intermittent fasting butrarely discuss the possible downsides. (Many people do not realise how much water is in food and some fail to compensate for this as they fast, leading to dehydration. More seriously, intermittent fasting has been associated with eating disorders, especially in young people.) Luxury hotels and health retreats offer fasting packages, costing thousands of dollars, where clients are put on low-calorie liquid diets, accompanied by mud wraps and massages.
In these situations, people are clients rather than patients, and aren’t expecting or entitled to plans of care. Still, Samuel Klein, the director of the Centre for Human Nutrition at the Washington University School of Medicine, advises people engaging in fasting treatmentsto be vigilant: "Unfortunately, nutrition is very open to a lot of things that are not evidence-based."
A scientist’s life is boring, full of meetings and computer time," Longo told me. We were in his sparsely furnished office at IFOM in Milan on a warm October morning, a few days before he was due to head back to America to teach at USC. Wearing black-framed reading glasses, he tightened his lips in concentration as he responded to emails and sent voice notes to fellow researchers. At one point the newest addition to his team of PhD students came in to tell Longo about her tentative plans for her time in his lab. Longo listened carefully before giving her advice: "Think of something that can make the biggest impact."
For the first few decades of his life, Longo himself had to work out how to do just that. He was born far from Calabria in the northern Italian city of Genoa, in 1967. His parents, Carmelo and Angelina, had left their hometown six years earlier in search of better opportunities; at the time, Calabria was one of the poorest areas in Europe. In Genoa, Carmelo worked as a police officer, while Angelina raised their three children, of whom Longo was the youngest.
Longo’s parents ensured that their children maintained a connection to Calabria. He and his siblings grew up eating the region’s traditional cuisine, which relies on seasonal local ingredients: legumes, pasta or cod with fresh vegetables, tomatoes and cucumbers generously doused in olive oil. Angelina also took the children to Calabria every summer. In 1972, when Longo was five years old, the family went to visit his 70-year-old grandfather, who had cancer. He died while Longo was there. Longo remembers being conscious of the number of elderly people walking around Molochio and wondered why his grandfather had died comparatively young. Ever since, he told me, "[Death] has remained central in my thoughts as the biggest problem you’ll ever have in your life. If you have this problem, you are screwed."
As a teenager Longo dreamed of becoming a rock star rather than a scientist. He played Jimi Hendrix, Pink Floyd and Dire Straits tunes on his guitar, and began writing his own songs on the piano.Instead of hanging out with his friends after school, he studied English, hoping to master the language for future American tours. "He was weird," admitted Stefano Taffelli, a friend of Longo’s from Genoa. "Then I realised it was his exaggerated determination and that when he wanted to get something, he got it at any cost."
When Longo was 16, he moved to Chicago to live with relatives whose families had emigrated from Calabria. It took him some time to adjust: as he writes in his book "The Longevity Diet". "My spoken-language skills were so bad that the immigration official stamped ‘no English’ on my passport." But soon he was attending American high school, taking guitar lessons and exploring the city’s music scene. After three years, he moved to the University of North Texas College of Music, outside Dallas, to study jazz. To earn money to pay his tuition fees he worked at a petrol station, sold water-filtration equipment and fixed roofs. He even joined the army as a reservist tank driver (he was almost deployed to fight during the Gulf war in 1991).
"[Death] has remained central in my thoughts as the biggest problem you’ll ever have in your life. If you have this problem, you are screwed"
In 1988, a year into his degree, Longo was forced to direct the university’s marching band – in his view a humiliating task for a wannabe rockstar. It was then that he began to wonder whether he should do something else with his future. He had never stopped thinking about his grandfather’s premature death, and wanted to know why some people lived longer than others. So he switched his major to biochemistry. It might seem like a drastic shift – but Longo thinks that scientists should be just as creative and rebellious as musicians, even if that means disregarding their professors’ advice. "Those who teach [science] say that if you don’t do as taught, you’re doing everything wrong. The same concept applies to classical music and the conservatory," Longo said. (He is fond of metaphors mixing science and music. At one point, while describing to me an argument he had with another professor over who was the lead author on a paper, Longo said, "Articles are like songs or compositions. They have a composer who came up with it and that must be respected.")
After graduating in 1992,Longo went to the University of California, Los Angeles to do a PhD in biochemistry. His supervisor was Roy Walford, an authority on the relationship between ageing and nutrition. Walford, who had devoted his life to studying whether mice could live longer if they ate less, was viewed as a "little crazy", Longo said. For about a year they could communicate only through video calls because Walford was taking part in a bizarre science experiment in Arizona – he and seven others were sealed up in an "earthbound space station" called Biosphere 2, where they attempted to replicate Earth’s ecosystem as practice for eventually building one on other planets. The experiment was controversial: due to meagre crop yields, the "crew" lost a lot of weight (something that Walford, given his belief in the health benefits of calorie restriction, encouraged) and suffered from low morale as a result.
"If I tell you, fast ten days a year, and I give you everything in a box, ready, I think most people might say ‘yes, I can do it’"
Longo wanted to build on Walford’s research by comparing the molecular differences between mice whose calories had been restricted and those who had been allowed to eat what they wanted. But Longo wasn’t convinced at the time by Walford’s hypothesis that long-term calorie restriction was the best way to extend human longevity.First, Longo felt that most people did not have the discipline or willpower to fast consistently. Second, it wasn’t clear which genes in mice played a role in the ageing process, and whether there were equivalent ones in humans. Longo decided to track down those "ageing" genes. He would start small, isolating them in one-cell organisms such as yeast, then would move on to more complex organisms and eventually to humans themselves.
In his lab, Longo cut nutrition to yeast cells to see how they reacted. He discovered that if he simply moved them from a liquid rich in sugars to water, their lifespan doubled. He realised that sugar activated certain genes that are generally understood to accelerate ageing in yeast. Sugar also prevented the yeast from being able to defend itself against oxidation, which can damage the DNA within a cell.
When Longo tried to publish his results, his papers were rejected. His peers took issue not only with his conception of the topic – many didn’t believe that starving any organism was a sensible way to study ageing – but also the form of measurement that he had used. At the time, most scientists studied yeast through its replicative life span, which measures how many times a cell can divide itself. Longo instead proposed using the chronological life span, which measures how long non-dividing cells can survive under different conditions. Today, chronological life span is widely accepted in the field. Frank Madeo, a professor of biochemistry at the University of Graz, Austria, who also studies cell death and ageing, told me that "back then, [Longo’s approach] was kind of against the flow."
A demoralised Longo turned towards other pursuits. Throughout the 1990s, he toured with his rock band, called DOT. He lived in a townhouse in Santa Monica and drove a vintage red Ferrari, which he had bought with the proceeds of his part-time job – translating Italian legal documents into English. "I was too poor to even buy [car insurance], but also embarrassed to have a Ferrari at my age, so I almost never got it out of the garage," Longo said.
Longo recalled this period of his life with a mixture of bitterness and self-righteousness."I decided to work on a micro-organism that didn’t interest anybody, and, within the work that was being done on that micro-organism, I chose to work on ageing and starvation, which were absolutely ridiculed," he told me. "But I was convinced. And thank goodness, because I totally guessed it right."
After seven years of rejections and rewrites, Longo’s paper on yeast cells was published in Science, one of the world’s top academic journals, in 2001. By demonstrating that there were genes regulating ageing in yeast – and that byde-activatingthem, the yeast lived longer – Longo became one of the first scientists to describe an anti-ageing pathway in any organism."It was a classic," said Caleb Finch, a professor of gerontology at USC and a mentor of Longo’s. "That was his own work."
The success of his paper on yeast cells did wonders for Longo’s career. Later in 2001 he became an assistant professor in gerontology at USC, where he began to research whether fasting could help with cancer. Longo was inspired not only by the memory of his grandfather’s early death, but also by his encounters with a young Italian girl, who had come to America for cancer treatment. Longo became close to the child and her family, and was deeply affected when she died, some three years earlier."Without meeting that five-year-old, I don’t know that I would have started working on cancer," he said.Longo had a hunch that fasting "could slow the cancer down"; he also wanted to find out if it could mitigate the side effects of chemotherapy.
Longo’s teamfound thatfasting shielded mice’s healthy cellsfrom the toxic drugs and enhanced chemo’s effectiveness against tumour cells, which continued to absorb the drugs meant to kill them. "I was quite shocked because I didn’t expect such a striking result," said Lizzia Raffaghello, a researcher at Los Angeles Childrens’ Hospital who conducted the research with Longo. "[Longo] probably already had it clear in his head and it was just a confirmation of what he thought." In 2008 Longo and Raffaghello published their findings in Proceedings of the National Academy of Sciences, a peer-reviewed journal.
Eric Ravussin, a professor at Louisiana State University, said, "I love what Valter is doing, but let’s put it this way, that’s not been rigorously tested to be a public-health message"
Not surprisingly, Longo’s research attracted a great deal of media attention, and he started to be contacted by cancer patients who were interested in fasting themselves. In 2009 Longo developed the beta version of his first fasting-mimicking diet, which was in part funded by the National Cancer Institute and the National Institute on Aging. The food for this FMD – which was initially intended only for cancer patients and was administered during clinical trials – was prepared in a Los Angeles restaurant, sometimes even by Longo himself.
It was around this time that Longo realised his FMD also represented a commercial opportunity. That same year, he launched a company, L-Nutra; by 2016, it was selling its first "fasting kits". In marketing a tweaked version of his cancer FMD to the general public, Longo hoped to make fasting easy for anyone who wanted to live longer and healthier. "If I tell you, fast ten days a year, and I give you everything in a box, ready, I think most people might say ‘yes, I can do it,’" Longo told me.
As well as its fasting kits, L-Nutra now sells supplements and nutrition bars, and even a Nutella-like paste called "longevity spread" – all derived from a mix of ingredients patented by Longo. The company’s best-known product, the ProLon 5-Day Diet, costs €199 ($216); on the basis of several clinical trials that Longo has conducted, the company recommends that most customers do the boxed diet 2-3 times a year. (L-Nutra claims to have sold 1m ProLon units in the past 9 years.)
Longo’s commercial pursuits have raised eyebrows among fellow scientists. He openly uses ProLon in his clinical studies, which some see as a red flag.According to Francesco Sofi, a professor in food science and clinical nutrition at the University of Florence, this represents "an important conflict of interest". (Longo claims that his earnings from L-Nutra, of which he owns 40%, and from the sale of his books are given to the two foundations he has founded – Create Cures Foundation in the US and Fondazione Valter Longo in Italy. These foundations, which conduct longevity research, also donate ProLon boxes to patients who can’t afford them.)
Longo’s findings have also been called into question. A meta-analysis, conducted in 2022, of nine studies – including one of Longo’s – that investigated the relationship between FMDs and chemotherapy found that there was no evidence that fasting was better than a regular diet in preventing side effects. Many oncologists advise that patients follow a diet rich in calories and proteins during chemotherapyto maintain their physiological functions.
In 2020 Sofi published a paper in the International Journal of Food Sciences and Nutritiondiscussing the limitations in Longo’s clinical trials, including the small number of enrolled participants."The transition from experimental studies on yeasts, cells and mouse models to clinical studies on humans occurred too quickly and without a solid scientific basis," Sofi told me. Eric Ravussin, a professor at Louisiana State University, agreed. "I love what Valter is doing, but let’s put it this way, that’s not been rigorously tested to be a public-health message," he said.
Other scientists are more generally opposed to FMDs, on the basis that restrictive eating can endanger long-term health. Benjamin Horne, an epidemiologist at Salt Lake City’s Intermountain Heart Institute, has found in his own research that those who fasted have lower chances of developing heart diseases and diabetes. Yet he remains concerned for the safety of his patients. "What induces the benefit in ketogenic [high-fat, low-carb] diets and fasting diets is that stress is put on the body," he explained.
And for those living with chronic diseases, that stress can lead to blood clotting or strokes. Like Sofi, Horne cautions against conflating the outcomes in animal studies with those in human ones: "Animal data are useful for directing researchers on what type of studies they should do in humans, but it should be human data that are used to direct human behaviour and human choices and human health interventions."
I put these criticisms to Longo. He thinks the desperation of sick patients justifies a more gonzo approach to possible treatments."If you are at stage 4 of cancer, and the oncologist has no more valid solutions, he should say, ‘Try this because there are a lot of studies on animals and some clinical studies.’ But this doesn’t happen," Longo complained. "Instead, the oncologic community says ‘no, you have to wait, you have to die, and maybe in ten years you’ll be able to use it.’" (In fact, in some cases of end-stage cancer, oncologists can be more flexible in their advice.)
Longo’s goal, ultimately, is"to make everybody reach 110 years, not only those who are born predisposed to get there." (He himself fasts, using ProLon boxes, a couple of times a year; otherwise, he follows his "longevity diet" religiously.)Longo’s professional bullishness is reminiscent of his idol, Elon Musk, whose "disruptiveness" he admires. According to Longo, without Tesla, Musk’s company, making electric cars en masse, these vehicles would have never gone mainstream. Longo thinks that L-Nutra is like Tesla: a brand that can bring fasting to the masses.
The company’s website asserts that it is at the forefront of a "nutritech revolution", vocabulary that is seemingly drawn from Silicon Valley. Yet Longo claims that he is not interested in replicating the desperate attempts by the super-rich to prolong human lifespans (like those of Bryan Johnson, a multi-millionaire entrepreneur, who made headlines last year for disclosing that he took blood plasma from his 17-year-old son in hopes of extending his own life – all part of the marketing for his longevity product). As Longo put it, he does not want to come up with another "biohacking strategy that may fall apart tomorrow".
Longo thinks that L-Nutra is like Tesla: a brand that can bring fasting to the masses
Even so, it could be some time before Longo’s ideas are accepted by his peers. His longevity study in Varapodio is progressing slowly: a year after his presentation to the town, only 272 people out of the desired 501 have enrolled. (His team has until this summer to reach the recruitment goal.) The study will probably not be completed until 2025. And even then, its results may not be viewed as entirely valid. According to Ravussin, the professor at Louisiana State University, the study would need to be at least a year long and involve many more people in order to be considered sound enough to become part of common medical advice about fasting.
I wanted to find out whether fasting was as easy as Longo claimed it would be. (L-Nutra provided me with a ProLon 5-Day Diet for the purposes of this article.) The diet is shipped inside the kind of sleek white case you’d expect to contain a Macbook. Inside are five numbered boxes, each containing roughly the same three pre-packaged meals for every day of the fast. Rather than asking clients to abstain from food entirely – a terrifying prospect to many – ProLon claims to trigger a "fasting state" from a limited amount of sustenance. On the first day, the plant-based, gluten-free meals contain a total of 1,100 calories; on the latter four, only 725 calories. (On average, women need around 2,000 calories a day and men 2,500.)
The menu looked grim. Breakfast was a crunchy nut bar and a cup of spearmint lemon tea; lunch was a handful of pitted green olives, a mushroom soup powder (that I mixed with water and microwaved for two minutes), a multi-vitamin pill and a cup of hibiscus tea; an afternoon snack was more olives and another cup of spearmint tea; dinner was another powdered vegetable soup, more hibiscus tea and a measly23 grams of a "healthy" chocolate bar.
The food lived up to my bleak expectations. I developed a bad headache, probably from caffeine withdrawal, that only went away only on day three. The soups, which had too much onion for my taste, were slightly sickening. I slowly savoured those few green olives, the only thing in the box I truly enjoyed eating. On night four, I dreamed of a margherita pizza. (In a study of 131 Dutch women with early-stage breast cancer, which Longo helped structure, only 20% followed the very low-calorie, low protein FMD through all eight cycles of chemotherapy. Many cited the unappetising nature of the food as a reason for quitting.)
By the end of the fast, I had lost 3.5kg, and maybe some of my sanity.Yet I also understood for the first time why some people feel accomplished while fasting: I felt lighter, healthier, closer to the world around me, and newly conscious of a strength I didn’t know I possessed. Savouring my first post-fasting meal, I thought I had caught a glimpse of what Longo’s ideas could mean for improving my longevity. But I also knew how difficult it would be for me (or realistically, anyone) to commit to a lifelong regular fasting regimen – especially if that meant eating powdered mushroom soup until I reached 110 years old. ■
Agostino Petroni is a writer based in Rome. His work has appeared in publications such as National Geographic, the BBC and the Atlantic
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