Thanks to earlier detection and much better treatment options, cancer today is more survivable than ever. But we are still a long way from curing cancer across the board for all types of cancer with equal outcomes. If you caught my podcast from several episodes back on improving cancer survival with diet and lifestyle choices, I covered the broad lifestyle habits linked with improving cancer survival odds. I also touched briefly on many of the so-called ‘cancer cure’ diets that abound on the Internet. So, for this podcast, I’m going to home in on one that is getting a lot of attention: and that’s the ketogenic diet.

Ketogenic diets are just one of an endless variation of low-carbohydrate, high-fat diets that are currently popular for weight loss. Designed to restrict carbohydrates to such a low level that greater amounts of ketone bodies (which are metabolic by-products from fat metabolism) are produced to fuel the body. A bit of digging around on the internet will also find claims that keto diets are also being promoted as a ‘cancer cure’ diet.

This link can be traced back to the 1920s and the observation by 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 has been called the Warburg effect. And a fun-fact side detour here, knowledge of the Warburg effect resulted in the development of the widely-used cancer detection method called positron emission tomography or PET scan. The PET scan uses radioactive isotopes of glucose with the knowledge that cancer cells exhibit higher rates of glycolysis so this helps pinpoint tumours with advanced imaging tools.

Back to keto cancer. Because cancer cells take up and metabolise more glucose than normal 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 CHO restriction, and specifically 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 postulated that a ketogenic diet could slow down angiogenesis - which is the generation of new blood supply - so in this case, it could help deprive a tumour of the nutrients it needs to grow from restricting its blood supply.

But is there merit in trying to keep blood glucose levels to help reduce the fuel available for cancer cells? Most of the evidence for this has been from rodent and cell culture studies. And the results have been mixed with some studies showing an anti-tumour effect from a ketogenic diet while also helping to augment chemotherapy drugs to work better. While 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 which I’ll link to in the show notes found that 60 percent of the preclinical 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. https://pubmed.ncbi.nlm.nih.gov/31399389

So, it may depend on specific tumour characteristics whether a ketogenic diet will be of benefit or not. And some of this research also highlighted the importance of optimising the composition of the ketogenic diet to enhance its efficacy, by increasing the proportion of fat or supplementing with MCTs or omega-3 fatty acids.

And since most of this pre-clinical research is in animal models involving grafting of tumours they are very removed from human physiology. So, it certainly should make any person take heed that the effect of low-CHO 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. But most preclinical and some clinical studies support the use of the ketogenic diet as an adjuvant cancer therapy that could be used in some situation to support current treatment protocols.

There have though been very few studies of ketogenic diets for the treatment or prevention of cancer in humans outside of a few pilot 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 which is hardly surprising as was already well known, but it does point to the feasibility and tolerability of using a ketogenic diet in this patient group. But this is by far from universal 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.

And putting all this human clinical research into one place, a systematic review has just been published in the last few weeks which I’ll link to in the show notes. https://link.springer.com/article/10.1007/s10238-021-00710-2

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 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 only three of these studies were of a randomised controlled trial design. And of note, in these three RCTs studies, they found a greater amount of weight loss in those people on the ketogenic diet, which is actually 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.

And 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 if a ketogenic diet improved survival and even then, it was in a subgroup of patients 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 with research papers that can only report on positive findings from a sub-group as if you slice and dice your data up enough, it is possible some significant finding will come up by chance.

In observational studies included in the review, only 5 studies met the grade that 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 was the conclusion of the review which I’ll read 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.”

Several clinical trials to further expand on the evidence base for the effect of a ketogenic diet in people with cancer are ongoing, and 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 a very 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 a few higher levels of evidence published before there could be a case to recommend this diet even in a specific type of cancer. 

It is by no means a bust for this diet, 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 then, 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.

Fasting

Just to finish off today, 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 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. Very early days for this, but is an area I’m watching with interest because the very 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, I’ve linked to a review paper from 2020 on the topic in the show notes https://pubmed.ncbi.nlm.nih.gov/33271979

So that’s it for today’s show. You can find the show notes either in the app you’re listening to this podcast on if it supports it, or else head over to my webpage www.thinkingnutrition.com.au and click on the podcast section to find this episode to read the show notes.

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I’m Tim Crowe and you’ve been listening to Thinking Nutrition.