Of all the claims made about ketogenic diets, it is ‘curing cancer’ that is the standout and most emotive one. In this blog post, I look at the evidence behind that claim.
Thanks to earlier detection and much better treatment options, cancer today is more survivable than ever before. But we are still a long way from curing cancer across the board for all types of cancer with equal outcomes. A bit of digging around on the Internet looking at diet and cancer will soon have you coming across all sorts of claims that keto diets can ‘cure cancer’. There are also some powerful personal story narratives to go with this.
Ketogenic diets are just one of an endless variation of low-carbohydrate, high-fat diets that are currently popular for weight loss. Low-carbohydrate diets are hardly a new thing. These diets have come into and out of popularity for decades just like fashion trends. Ketogenic diets are designed to restrict carbohydrates to such a low level that greater amounts of ketone bodies are produced. These ketone bodies are metabolic by-products of fat metabolism and have an important role as an energy source during starvation.
The rationale for ketogenic diets and cancer
The link between ketogenic diets and cancer can be traced back to the 1920s. It was Nobel Prize-winning physiologist Otto Warburg who observed that cancer cells take up more glucose than healthy cells and convert it via glycolysis to lactic acid. This characteristic of cancer cells is called the Warburg effect.
A fun fact side detour here: knowledge of the Warburg effect resulted in the development of the widely used cancer detection method of positron emission tomography or PET scan for short. A PET scan uses radioactive isotopes of glucose with the knowledge that cancer cells exhibit higher rates of glycolysis so will metabolise more of the glucose. This helps pinpoint tumours with advanced imaging tools.
Back to keto and cancer. Because cancer cells take up and metabolise more glucose than healthy cells, it has been speculated that reducing carbohydrate intake, and thus reduce glucose availability in the blood, might help prevent or treat cancer. Although I should add here that even protein contributes to blood glucose. And even an all-fat diet will still result in adequate glucose in the bloodstream as the body can make it from other sources. So, there is the theory, and then the reality of what may happen as you can’t starve yourself of glucose or you’d be dead.
Another possible mechanism by which carbohydrate restriction, and specifically to the level of a ketogenic diet, might slow cancer growth is through the generation of ketone bodies. There is some evidence that many cancer cells, unlike normal cells, cannot use ketone bodies as an energy source so this again could help deprive them of a fuel source.
And it has even been suggested that a ketogenic diet could slow down angiogenesis. Angiogenesis is the generation of new blood supplies. So here, a ketogenic diet could help deprive a tumour of the nutrients it needs to grow by restricting its blood supply.
But is there merit in trying to keep blood glucose levels low to help reduce the fuel available for cancer cells? Most of the evidence for this has come from rodent and cell culture studies. And the results have been mixed. Some studies show an anti-tumour effect from a ketogenic diet while also helping to enhance chemotherapy drugs. That’s the good news. Now the bad news. Other studies find that a keto diet actually promotes cancer progression as is the case with cellular models of melanoma.
One recent review of the preclinical studies in this area found that 60 percent of research studies reported an antitumor effect of a ketogenic diet. But 17 percent of studies did not detect an influence on tumour growth. And concerningly, 10 percent of studies reported adverse or pro-proliferative effects on tumour growth.
That certainly should make any person take heed that the effect of low-carbohydrate diets on cancer is by no means universally positive and may even be harmful. We are still a long way from knowing how this all plays out in humans. It may depend on specific tumour characteristics of if a ketogenic diet will be of benefit or not.
What do human studies say?
Most of the research into ketogenic diets and cancer sits in the preclinical research domain. These studies involve either cells grown in a laboratory or animal models that have tumours grafted on them. All of this is very removed from human physiology.
There have though been a small number of studies of ketogenic diets trialled for the treatment or prevention of cancer in humans. Most studies fall into the categories of pilot studies or case studies with a small number of subjects, so larger randomised controlled trials are still needed. Nevertheless, consistent findings from the research include a moderate reduction of blood glucose levels and induction of ketosis. This is hardly surprising as that is what ketogenic diets do by default.
But it does point to the feasibility and tolerability of using a ketogenic diet in the cancer setting. But mileage can vary with common reports in some studies of low adherence to the diet because of either poor tolerability of the ketogenic diet associated with nausea, fatigue or constipation or because patients stopped the diet because of tumour progression. So, it’s not a glowing report card for the diet in all cases, but then again, such symptoms are common in many people with cancer regardless of the diet followed.
The latest research into keto and cancer
Putting all the human clinical research into keto and cancer into one place, a systematic review has recently been published. The review looked at any studies that analysed the use, effectiveness and potential harm of a ketogenic diet in people with cancer of any age when used as either a sole or complementary therapy.
Showing just how small the research field is, even though 46 studies were identified, a total of just 770 patients were studied. So that’s a lot of small studies and case reports in the research field. And a minuscule number of just three of these studies were of a randomised controlled trial design. As a side note, in these three clinical trials, they saw a greater amount of weight loss in those people following a ketogenic diet. This is not a positive finding in a cancer group considering the big issue of unintentional weight loss and malnutrition in people with cancer undergoing active treatment.
Even with the amount of research included in the systematic review, it was only in just one single study where it was possible to make a call on if a ketogenic diet improved survival. Yet even then, it was in a subgroup of people with breast cancer, but the result was favourable. It is a big understatement to say that we really can’t extrapolate a conclusion from one well-controlled study that had to drill down into a subgroup of patients to see any benefit as some form of endorsement for this diet. I am always cautious of research papers that can only report on positive findings from a sub-group as if you slice and dice your data up enough, some significant findings may come up purely by chance.
In observational studies included in the review, only five studies met the grade where you could assess the survival benefit of a ketogenic diet in people with cancer. Two studies found no benefit. Two found a small benefit. And one study reported a worse outcome on cancer survival with a ketogenic diet. Hardly a ringing endorsement for those promoting such a diet as a ‘cancer cure all’. Just stop it, if it really worked that well then even the small amount of research covered in this review should be clearly detecting a big survival benefit – it didn’t.
Here is the conclusion of the review which I’ll quote verbatim from the paper:
There was no conclusive evidence for anti-tumour effects or improved survival. The majority of patients had significant weight loss and mild to moderate side effects. Adherence to the diet was rather low in most studies. Due to the very heterogeneous results and methodological limitations of the included studies, clinical evidence for the effectiveness of ketogenic diets in cancer patients is still lacking.
What does the future hold?
Several clinical trials to further expand on the evidence base for the effect of a ketogenic diet in people with cancer are ongoing. The results from these trials will be essential to further evaluate the feasibility of the ketogenic diet in clinical practice. Some of the strongest case reports of keto’s possible benefits have come from glioblastoma which is an extremely aggressive form of brain cancer. But it doesn’t seem to work that well on other kinds of brain cancer. And here, we are still talking about case reports, which is code for anecdotes. There needs to be higher levels of evidence published before there could be a case to recommend this diet even in a specific type of cancer.
Fasting and cancer
Just to finish off, I want to take a slight tangent to ketogenic diets in cancer and mention the related, but not identical area, of fasting during cancer treatment. Fasting is like a ketogenic diet on steroids as it removes all external fuel sources from the body.
There is some absolutely fascinating research work being done looking at how fasting during chemotherapy could improve treatment by promoting cellular regeneration, repairing DNA damage and reducing side effects like nausea and vomiting. It is very early days, but it is an area I’m watching with interest because the small amount of human clinical research so far points to fewer treatment-related side effects and hints of increased efficacy of chemotherapy with periods of short-term fasting done under medical supervision. If you want to delve more into this area, this review paper from 2020 will get you up to speed.
What it all means
It is by no means a bust for a ketogenic diet treating cancer, only that the hype is well in excess of the reality. But there is a possibility that it may be effective in some patient subgroups and for some types of cancer. Until more is known about for whom and when to use this diet, get your advice on diet during cancer treatment from those directly working in the area such as oncologists and clinical oncology dietitian – not over-hyped stories on the Internet promising a miracle cure for cancer with keto. If the evidence was there to support such claims, I would happily join the cheer squad.