In the ever-more masochistic world of wellness-boosting, pound-shedding diets, the latest trend involves putting your body into a controlled state of starvation known as “ketogenesis,” by cutting out nearly all carbs. If that doesn’t sound like your particular brand of torture, guess what? You’re already on it. Well, at least while you’re sleeping.
Two independent studies published Tuesday in the journal Cell Metabolism raise hopes that ketogenic diets, if followed full-time, do more than just slim waists. They also appear to improve the odds of living longer and remembering better … if you’re a mouse. The same effects have yet to be proven in humans, and plans for that are in the works. But in the meantime, self-experimenting biohackers (i.e. dieters) are collecting anecdotal evidence all around the world.
Every time you wake up from a solid snooze and exhale out the fiery iron breath of a thousand rotting apple cores, that’s the taste of the “keto” lifestyle. That smell is acetone, and a little bit of it in the morning is a normal sign of a healthy metabolism. Over millennia, humans evolved a backup energy production system, for when glucose—your body’s main fuel source—gets depleted. Like during a famine, or just a good long nap. The goal of keto diets is to switch your body over to to this alternative metabolic pathway not just at night, but during your waking hours as well. By limiting carbs to just a few grams per day, your body begins to rely on its fat stores instead, and voila, epic weight loss.
That works pretty well for things like your heart and lungs and muscles. But your brain—that electrical power suck, which consumes about a quarter of your daily calories—can’t burn fats. So in the absence of glucose, it snacks on something called ketone bodies, which are a byproduct of fatty acid metabolism in the liver, hence “keto” diets. Now, you don’t have to run a clinical trial to start selling keto cookbooks, and you don’t have to present statistically sound results to buy out late-night infomercial slots for bulletproof coffee. But the popularity of keto lifestyles has so far outstripped the scientific evidence for not only how it works, but even whether or not it works at all.
(Unless you’re an epileptic; the altered metabolism reduces levels of glutamate in the brain, which has been proven to lower the risk for seizures. In fact, the first ketogenic diet was developed by the Mayo Clinic as an epilepsy treatment.)
There have been some clues though, over the years, that ketone metabolism might have some additional benefits. Back in 2010, molecular biologist Eric Verdin changed the way people thought about ketone bodies—in particular, one called beta hydroxybutyrate, or BHB. Scientists in his lab at the Buck Institute for Research and Aging observed that BHB wasn’t just a passive fuel floating around the brain. It was sending out signals and modifying molecular pathways in the brain to reduce inflammation and other damage caused by free radicals. That got researchers thinking that BHB could have anti-aging properties—and so would ketogenic diets.
So three years ago, Verdin and other scientists at the Buck and UC Davis began raising young mice, feeding them standard lab chow until they were a year old. For some of them, that was the last time a carb ever crossed their lips. About a third of the mice went on a ketogenic diet, spending the next few years consuming 90 percent of their calories from fats and the rest from protein supplements. In one of the studies, that steady supply of soybean oil and lard made them live longer by about four months. In the other, the sugar-starved mice performed better than their carbed cohort at a variety of maze problems designed to test their memory and ability to recognize new things.
“We’re very excited to see such a profound effect on brain function,” says Verdin. But he says it’s important to remember that mice studies are just the first step. “Our results don’t imply this is going to work in humans. For that, we’ll need extensive clinical trials.”
In some ways, the mouse brain is a very good model for what happens inside a human skull. After all, electric signals zipping around a mouse brain have to follow the same laws of physics that they do inside a person’s. But there are some key differences when it comes to ketones. For one thing, humans have more capacity to metabolize the molecules than almost any other animal. Thousands of years ago, as early humans were gathering tubers and greens and learning how to kill big game, mice were doing what they’d done since the demise of the dinosaurs—eat seeds and grains. With such different systems for digesting and breaking down proteins, fats, and sugars, it’s far from sure that human brains will respond identically to an all-ketone-all-the-time routine.
“It’s a harder question to ask in humans, one that hasn’t been studied very extensively,” says Emily Deans, an evolutionary psychologist who specializes in the connections between nutrition and mental health. “We don’t have a good way to get into the brain to see exactly what’s happening with metabolism. Healthy people aren’t exactly going to line up for elective brain biopsies.”
Deans says what scientists really need are some well-controlled clinical trials to see how ketogenic diets impact people over the long term. She has hopes they might one day help some of her patients, who suffer from things like bipolar disorder and PTSD. But getting people to participate in a trial that takes away things that help to cope with their diseases—like candy and other pleasure-center-hitting foods—is no small task. That’s something Verdin has thought about too. Which is why his lab is already moving forward to capture the protective effects of ketogenic diets in something more palatable: a pill.
They’ve begun synthesizing precursors to BHB and feeding them to mice. After following the rodents for a few years, they’ll look to see if the molecule on its own provides the same protective effects as an all-Crisco diet. If it works, clinical trials would be next. And unlike a diet, which can’t be patented or easily monetized, a supplement could be something pharma companies (and bread-lovers) can get behind.