Can an extreme low carb diet be used as medicine?
Several studies in recent years have suggested that the ketogenic diet may work against a variety of diseases, such as epilepsy, Alzheimer's disease and cancer.
If you have heard of the ketogenic diet, an extreme low carb approach to eating, you may associate it with controversy and an alternative treatment for obesity.
Personal anecdotes in the media tell about astounding effects against obesity and type 2 diabetes. But the research is inconclusive, and we know very little about long term effects of such a diet. Many professionals warn against a diet which is so high in fat.
Nevertheless, there is a growing interest in this extreme high-fat diet among researchers. In 2019 alone, more than a thousand new research articles were written on the topic.
And these studies are no longer solely focused on obesity and diabetes, says researcher and clinical nutritionist Magnhild Kverneland at Oslo University Hospital.
“Researchers are looking at diseases such as Parkinson's, Alzheimer's, ALS, brain tumours, migraines and multiple sclerosis,” she said.
And epilepsy - which is the focus of Kverneland’s research.
This is a high fat diet, with a normal amount of proteins, and very few carbohydrates.
Under 20 grams of carbohydrates
A typical goal is for people to eat less than 20 grams of carbohydrates per day. This excludes foods that contain a lot of starch or sugar, such as bread, pasta, rice, potatoes, root vegetables, cakes, sweets, juices and fruits.
Other vegetables OK
Meat, fish and eggs contain few carbohydrates. The same is true for some dairy products, such as cream, sour cream and most cheeses. Fat-based sauces, oils and mayonnaise are often part of the diet. But a ketogenic diet need not be a butter-and-bacon diet. Many vegetables, typically those that grow above ground, contain few carbohydrates. Lettuce, cucumber, cabbage, cauliflower, squash and tomato can be consumed in a ketogenic diet. Avocado and many types of nuts and seeds also have low carbohydrates and a lot of beneficial fat.
The ketogenic diet has actually been used in the treatment of epilepsy since the 1920s.
It had been known that patients often had significantly fewer seizures if they lived on a very strict diet, where up to 90 per cent of calories came from fat and carbohydrate intake was less than 20 grams a day.
But a diet that is so different from normal is hard to follow. So when effective medicines began to emerge for the disease, using diet as a treatment went out of fashion.
Over the decades, a total of 25 different anti-epilepsy drugs have been developed. But research has also shown that these medicines do not work for everyone.
“About a third of patients don’t get an acceptable level of relief from the medicines. That’s a real challenge,” Kverneland said.
This is why researchers and therapists have brought back the old diet regimen. In 2008, the journal The Lancet Neurology published a ground-breaking study of children whose severe epilepsy couldn’t be controlled with medication.
“The study showed that the ketogenic diet had a much better effect than continuing with treatment as normal,” says Kverneland.
Now this type of treatment is part of what patients are offered in Norway, in situations where children don’t get enough help from medicines. The treatment is also increasingly used in adults.
Kverneland herself has studied how the diet works for adults with epilepsy. The study showed that a ketogenic diet was associated with fewer seizures in participants.
However, the impact was moderate, and there was a big difference from person to person. Some patients showed significant improvement, while some actually got worse.
The reason behind these varied results is likely that epilepsy itself is a very varied disease, with many possible causes. As well as another fascinating fact which Kverneland and collegues discovered in a study which was published in the journal Epilepsa last year:
The diet seems to diminish the effect of some of the epilepsy drugs.
Probably due to changes in the liver
"We found that the ketogenic diet affected the level of anti-epileptic drugs in the blood of adult patients," she said.
The effect is probably different for different drugs, but the diet did appear to reduce the effect for at least some of them.
“It’s important for doctors to keep this in mind, because it may also be true for other medical drugs,” she said.
The researcher is not yet sure why the ketogenic diet has this effect, but she suspects a high-fat diet is likely to affect the blood circulation rate in the liver, which is where medicines are broken down.
And it's a reminder of the dramatic changes that are actually happening in the body when we switch from a normal diet to a ketogenic diet, where fat intake is doubled or tripled.
Two energy systems
When you stop eating carbohydrates – which you usually get in large amounts from bread, rice, potatoes, root vegetables, fruits, beans and sweets – the body loses its main source of energy, glucose. It is glucose – blood sugar – which usually fuels your body’s cells.
When all the carbohydrates you have consumed are gone, your body is like a car in the middle of the highway, where the fuel tank is nearly empty.
Turns out nature provides for situations like this. The body is actually built a bit like a hybrid car. It has two parallel energy systems – one that runs on glucose, and one that runs on fat. So when the glucose system runs out of fuel, the fat system takes over.
This dual system has been absolutely necessary for survival during much of human history.
As the body runs out of glucose from food, it begins to consume its fat stores. Fatty acids are released from the fat cells in the body and are converted into ketone bodies. Cells can use these ketones as an energy source, instead of glucose.
“This is a natural condition that has contributed to the survival of our species. Evolutionally, we are well adapted to it,” says Kverneland.
When our ancestors had bad luck hunting or gathering fruits or other wild foods, they had to endure days, maybe weeks without food. They still needed to be able to operate both physically and mentally so that they could eventually get the food they needed.
This is when ketone bodies played an important role.
“The body sees ketone bodies like a super fuel. They provide more energy per unit than glucose,” says Kverneland.
At the same time, the body makes many changes to allow this alternative energy system to work.
It is common for people who switch from the glucose system to the fat system to feel quite tired during the first days or weeks. But then the body gets used to the new fuel system and works normally.
In addition, it appears that the changes the body makes during this shift can have positive effects on some diseases.
This fact has also been known for a very long time.
Similar to a fast
Much of what we know about ketone bodies is quite new. But humans have long known that hunger and fasting can have a positive effect on your health.
More than 2000 years ago, fasting was used as a treatment for epilepsy.
The only problem is that fasting is not an attractive way to treat a long-term illness. That’s where the ketogenic diet comes in.
When you turn off the body’s supply of carbohydrates and instead only give it fat to burn, it will switch over to the alternative energy system, even if you aren’t starving.
“What’s exciting about the ketogenic diet is that it mimics the body's reaction to fasting,” says Kverneland.
It was precisely this idea that led researchers to test the ketogenic diet as a treatment for epilepsy, in the early 1900s. And it turned out that the hypothesis was correct.
And in recent years, as we have learned more about what happens when the body uses fat as its primary fuel, researchers have wondered: Can other diseases be treated with this special diet?
Alzheimer’s disease a possibility
One of the areas where researchers are increasingly interested in this approach to treatment is Alzheimer's disease.
There are good reasons to suspect that the diet may have an effect here.
Previous research has suggested that people with Alzheimer's have problems with the processes that allow glucose to be used by brain cells. To continue with the car analogy: The engine can no longer take in gasoline properly.
But maybe the energy system that burns fat still works? If so, could it provide enough energy to fuel brain cells via the alternative energy system and the super-fuel ketone bodies?
A few small studies have been done where people with mild or moderate Alzheimer's have followed a ketogenic diet or taken supplements containing ketone bodies. The approach has shown positive effects on symptoms, according to a review published in the journal Neurotherapeutics in 2018.
But the treatment did not work for everyone, perhaps because we have different genes. Researchers need to do more and larger studies before they can say anything for sure.
There have also been interesting results for several neurological disorders, including ALS, according to the Neurotherapeutics review.
ALS, or amyotrophic lateral sclerosis, is linked to disorders in the body’s energy conversion system and uptake of glucose by the brain and nervous system. Animal studies have suggested that a ketogenic diet may slow down or improve symptoms.
Other studies have suggested that a ketogenic diet might also help with multiple sclerosis and Parkinson's disease.
Another area where there is an increased interest in this treatment is for headaches.
May help with migraines
According to the Neurotherapeutics review, several studies have shown that a ketogenic diet can help people who get migraines and cluster headaches.
In this situation, however, it’s likely that energy supply isn’t the problem. One of the reasons for symptoms in both epilepsy and migraines is that nerve cells tend to send signals too easily.
Previous studies have shown that ketone bodies appear to regulate neurotransmitters — the substances that cells use to send signals from one nerve cell to the next.
Some studies on humans suggest that the ketogenic diet can have a rapid effect on migraine attacks, according to a 2017 review published in the journal Neurological Sciences.
But the documentation is far from good enough. Here too, more studies are needed, to both show whether the diet actually works on sick people, and how it actually works in the body.
The same is true of a recent area where ketogenic diets have been shown to have an effect — cancer.
May work with cancer treatment
Researchers know that a number of different cancer cells depend on glucose as an energy source.
From there, the next step is obvious: Could you starve a cancerous tumour by taking away its fuel source, while keeping the body’s healthy cells alive with energy from fats?
Several studies have been done on cells and animals suggesting that a ketogenic diet can have a significant effect, especially in combination with traditional treatments such as chemotherapy and radiation therapy.
A few studies in people have pointed in the same direction.
The diet appears to enhance the effect of some cancer treatments, as well as protect patients from the severe weight loss that some cancer patients experience, researchers wrote in a review published in Molecular Metabolism in 2019.
The researchers concluded that the findings to date suggest the ketogenic diet can help with a variety of cancers.
However, several cancer doctors have previously warned cancer patients to stop with this extreme diet. They are concerned that the restrictive diet will make life difficult, and that patients will have trouble consuming enough food.
We also do not know which types of cancer the diet might help with. There are also studies that show no effect, and some studies in animals have indicated that the diet can even aggravate cancer.
Inflammation and intestinal flora
All in all, it's too early to say for sure what role the ketogenic diet could play in the treatment of different diseases, and what effects it has on the body.
Perhaps many mechanisms are involved.
For example, some studies have shown that a ketogenic diet can curb inflammation, which is often a hallmark of a variety of diseases.
Other studies show that the special diet leads to changes in the gut flora. Much research has suggested that the gut microorganisms play an important role in various diseases.
Food as medicine
Dietary changes can seem mundane, because they concern food and are something we can do on our own. But it may be more appropriate to think of the ketogenic diet as a drug.
It’s a treatment that has medical effects. But it can be very demanding to follow. In addition, the diet can have side effects that in the worst case can be dangerous.
For example, it is known that the ketogenic diet can cause digestive problems and increase LDL cholesterol, which is linked to a higher risk of heart disease.
And when Norwegian researchers put mice, whose cells' energy turnover had been damaged, on a ketogenic diet, the animals actually got worse from the treatment, according to a 2016 study in the journal Neurobiological Aging.
And much like any drug, the ketogenic diet will work differently from person to person.
Kverneland says there are large individual differences in the effect of the ketogenic diet on epilepsy. When patients in Norway try the diet, they receive thorough guidance and follow-up.
“We take blood tests and monitor the effects and side effects,” she said. “Some see a truly amazing effect. Then everyone is happy. But the response is different from patient to patient.”
“What would be nice would be if we could predict who is going to see an effect. It's something I hope we can do more research on,” she said.
Translated by Nancy Bazilchuk
I. D. Meira, et al: Ketogenic Diet and Epilepsy: What We Know So Far, Frontiers in Neuroscience, January 2019.
D. D. Weber, et al: Ketogenic diet in the treatment of cancer – Where do we stand? Molecular Metabolism, March 2020. Summary.
M. Kverneland et al: Pharmacokinetic Interaction Between Modified Atkins Diet and Antiepileptic Drugs in Adults With Drug-Resistant Epilepsy, Epilepsia, November 2019. Summary.
M. Kverneland, et al: Effect of Modified Atkins Diet in Adults With Drug-Resistant Focal Epilepsy: A Randomized Clinical Trial, Epilepsia, June 2018. Summary.
T. J. W. McDonald, M. C. Cervenka: Ketogenic Diets for Adult Neurological Disorders, Neurotherapeutics, October 2018. Summary.
P. Barbanti et al: Ketogenic Diet in Migraine: Rationale, Findings and Perspectives, Neurological Science, May 2017.Summary.
K. H. Lauritzen, et al: A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain, Neurobiology of Aging, December 2016. Summary.
Read the Norwegian version of this article at forskning.no