Eating a high-fat, low-carb diet could raise the risk of developing liver cancer within just twenty years, concerning new research has suggested.
Referred to as a ‘keto diet’, devotees claim that it can aid rapid weight loss without feelings of hunger—but experts now say fatty diets can fundamentally alter liver cells, increasing the risk of cancer.
US scientists found that when the liver is repeatedly exposed to a high-fat diet, its cells shift into a more primitive state.
Whilst this change helps cells withstand the stress caused by excess fat, it also makes them more vulnerable to disease.
‘If cells are forced to deal with a stressor such as a high fat diet over and over again, they will do things that will help them to survive, but at the risk of increased susceptibility to tumorigenesis [when normal cells mutate and become cancerous],’ Professor Alex Shalek, director of the Institute for Medical Engineering and Sciences, and study co-author, explained.
The team hopes that by targeting these changes early, doctors will be able to reduce the risk of tumour formation in people who are particularly vulnerable.
A keto diet involves almost entirely avoiding ingesting carbohydrates in order to trigger a state of ketosis, which is when the body burns stored fat for energy, which in turn helps people lose weight.
Carbohydrates are a macronutrient (along with fat and protein) and are found in everything from grains to starchy vegetables and fruits.
High-fat diets have long been linked to steatotic liver disease, whereby excess fat builds up inside the liver causing inflammation, liver failure and ultimately cancer.
In the study, published in the journal Cell, researchers fed mice a high-fat diet and used cell-sequencing to analyse how their livers responded.
Early on, liver cells called hepatocytes were shown to activate genes to help them survive- reducing the likelihood of cell death and promoting growth.
However, at the same time, genes essential for normal liver function were shut down.
‘This really looks like a trade-off, prioritising what’s good for the individual cell to stay alive in a stressful environment, at the expense of what the collective tissue should be doing,’ Constantine Tzouanas, Harvard-MIT graduate and study co-author said.
By the end of the study, nearly all mice fed a high-fat diet had developed liver cancer.
The researchers found that when liver cells adapt in this way, they are more likely to become cancerous if a damaging mutation later occurs.
Tzouanas said: ‘These cells have already turned on the same genes that they’re going to need to become cancerous.
‘Once a cell picks up the wrong mutation, then it’s really off to the races and they’ve already got a head start on some of those hallmarks of cancer.’
After uncovering these cellular changes in mice, the team turned their attention to people with various stages of liver disease.
They found that, over time, genes required for normal liver function deteriorated, while genes linked to cell survival thrived, allowing them to accurately predict patient survival outcomes.
‘Patients who had higher expression of these pro-cell-survival genes that are turned on with a high-fat diet survived for less time after tumours developed,’ Tzouanas explains.
‘And if a patient has lower expression of genes that support the functions that the liver normally performs, they also survive for less time.
The scientists highlighted that whilst most of the mice developed cancer within a year, this process is much slower in humans, unfolding over around 20 years.
But, they added, this time frame can vary based on lifestyle factors such as alcohol consumption, and overall health – with excessive drinking and viral infections both pushing liver cells toward an ‘immature’ state, increasing the risk of cancer.
This is because when liver cells exist in a less mature state, they are more likely to become cancerous if a damaging mutation occurs later.
The team will now investigate whether this damage can be reversed through a healthier diet, or using GLP-1 weight loss drugs such as Mounjaro.
Prof Shalek said: ‘We now have all these new molecular targets and a better understanding of what is underlying the biology, which could give us new angles to improve outcomes for patients.’
A keto diet often consists of 75 per cent fat, 20 per cent protein and only 5 per cent carbohydrates.
By contrast, the NHS’s healthy balanced diet advice advocates for 30 per cent fat, 15 per cent protein and over 50 per cent carbohydrates.
Despite multiple studies pointing to the potential dangers of a keto diet it has become increasingly popular. A number of celebrities such as Gwyneth Paltrow, Jennifer Aniston, Halle Berry and Kourtney Kardashian have spoken about being on the low-carb diet in the past.
Where liver disease was once largely confined to the elderly and heavy drinkers, it is now rising rapidly among younger adults.
The British Liver Trust estimates the condition may now affect one in five people in the UK—though experts have warned the true figure could be as high as 40 per cent.
Worryingly, around 80 per cent of those affected remain undiagnosed, as the disease often has no obvious symptoms—or it has symptoms that are mistaken for less serious problems.
Around one in four patients will develop a more advanced form of the disease resulting in irreversible scarring of the liver, ultimately resulting in organ failure and cancer.
But experts are hopeful that weight loss jabs like Mounjaro will transform liver disease treatment, helping the liver burn excess fat that increases the risk of disease.
