The ketogenic (keto) diet is one of the most widely adopted in the world, holding a global market value of $12.45bn and a projected five-year CAGR of 5.8%, according to Grand View Research. Now, research from Stanford University, could be set to boost the diet’s popularity even further.
New discovery in ketogenic diet
The ketogenic diet, commonly known as the keto diet, is already hugely popular, for its widely known weight loss benefits. However, a collaborative research team, led by scientists at Stanford University, is now tackling the unanswered questions surrounding ketosis. In particular, the team focused on the underlying chemistry of ketones themselves. And, in doing so, they discovered a previously unknown metabolic pathway, and a family of keto metabolites, potentially rewriting the current understanding of how ketosis influences metabolism, including in the brain.
“It turns out ketosis is not a monolithic state,” says Jonathan Long, an associate professor of pathology at Stanford Medicine. “There’s a lot more complexity and nuance in how the body processes ketone molecules, and this could explain some of its more intriguing effects.”
When deprived of glucose - the body’s primary energy source - it shifts gears and begins breaking down fat to produce ketones as an alternative fuel. Central to this process is beta-hydroxybutyrate (BHB), the most abundant ketone. But, until now, scientists believed ketosis followed two main biochemical pathways - ketogenesis, which produces beta-hydroxybutyrate in the liver, and ketolysis (or ketone oxidation), which consumes beta-hydroxybutyrate for energy throughout the body. These pathways were thought to tell the whole story.
The research team weren’t so sure, and so decided to take another look at what ketones, particularly beta-hydroxybutyrate, were doing in the body, asking the questions where do they come from and where do they go?
How the study was conducted
In a series of experiments on both mice and humans, the researchers manipulated the availability of beta-hydroxybutyrate, to explore how it influences metabolism and energy balance. What they found was a previously unknown metabolic ‘shunt pathway’, where enzymes attach beta-hydroxybutyrate to amino acids, producing a family of compounds they dubbed BHB-amino acids.
“If pathways are like the highway system, shunts are the off-ramps,” explains Long. “What we’re saying is, this is not the main pathway that’s directing traffic, but it gets you somewhere very interesting and unusual off the main road.”
The team concluded that the discovery of this ketone shunt suggests ketones have additional, previously unrecognised roles within the body’s metabolic landscape. But the critical question remained - are they inert byproducts, or do they actively influence the body’s response to ketosis?
To answer these questions, the researchers focused on the brain. The reason for this being that when people are in ketosis, hunger decreases.
“When I’m fasting or losing weight, I don’t feel as hungry,” says Long. “That’s a well-established aspect of ketosis, tied to the neurobiology of feeding and energy balance.”
They also noticed the metabolites they were studying chemically resembled another molecule, previously discovered by the research team, which is known to regulate hunger and appetite - Lac-Phe.
Lac-Phe is produced in the body after sprint exercise, and functions to reduce appetite. This chemical resemblance guided their investigation, raising the question of whether these ketone metabolites play an active role in appetite suppression and weight regulation under ketosis conditions.
The researchers found that BHB-amino acids suppress feeding behaviours and promote weight loss, revealing a potent link between ketosis and energy regulation.
“This third, shunt pathway turns out to be important for the regulation of appetite and ketosis-associated weight loss,” says Long.
What this means for the future of keto
By uncovering this previously unknown pathway, the researchers have created an opportunity to revisit longstanding questions surrounding the mechanisms behind the ketogenic diet’s benefits.
For example, while it’s established that the ketogenic diet is effective in controlling seizures in children with drug-resistant epilepsy, it remains unclear as to whether other potential benefits, such as improved cognition or metabolic health, are to be trusted.
And if they are proven to be effective in treating these additional health issues then we could see a huge spike in adoption of the keto diet. And this, in turn, could lead to a rise in the sales of foods which support this diet.
What is a ketogenic diet?
The ketogenic diet, better known as the keto diet, is a low-carbohydrate, high fat and moderate protein diet, which shifts the body’s metabolism from using glucose as the main fuel source to burning fat and producing ketones for energy.
What are ketones?
Ketones are a type of chemical that the liver produces when it breaks down fats. The body uses ketones for energy during fasting, long periods of exercise or when it does not have access to carbohydrates.
There are four versions of the ketogenic diet:
- Standard ketogenic diet (SKD): This is a very low-carbohydrate, moderate protein and high fat diet. It typically contains 70% fat, 20% protein, and only 10% carbohydrates.
- Cyclical ketogenic diet (CKD): This involves periods of higher carbohydrate re-feeds, such as five ketogenic days, followed by two high-carbohydrate days.
- Targeted ketogenic diet (TKD): This diet allows you to add carbohydrates around workouts.
- High protein ketogenic diet: This is similar to a standard ketogenic diet but includes more protein. The ratio is typically 60% fat, 35% protein, and 5% carbohydrates.
Source: A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites
Published online: 12 November 2024
DOI: 10.1016/j.cell.2024.10.032
Authors: Maria Dolores Moya-Garzon, Mengjie Wang, Veronica L Li et al.