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Fundamental flaws in using a Ketogenic diet to fight cancer

A Ketogenic Diet or Keto Diet, which sets out to starve cancer cells of their food by providing a high fat, low carbohydrate intake, may be popular but it is scientifically and practically flawed, with hardly any quality research showing it increases survival times.

From both a scientific perspective AND from observing UK cancer patients using it, I suggest there are at least five main concerns or flaws (writes Oxford University Biochemist, Chris Woollams):

i) Not all cancer cells feed the same way. While a primary breast cancer might need glucose for its fuel, prostate cancer cells tend to use glutamate as the main fuel, and liver cancer cells can even use ketone bodies and ketolysis to progress (1). Starving cancer may also depend upon how advanced the cancer is. A meta-analysis of breast cancer (2) found a diverse picture with only some studies suggesting potential benefits of the KD in inhibiting tumor growth and improving treatment response,  Robust clinical trials providing clear evidence of the Keto Diet’s efficacy as a stand alone therapeutic approach in BC are still lacking. The Keto diet may not be a consistent and universal panacea for all cancers at any stage.

ii) Glutamine and glutamate are also cancer cell energy providers: Glutamine, an amino acid in proteins (animal and plant) converts to glutamate, which behaves rather like the reserve tank of fuel in many cancers, but the primary source in prostate cancer and some brain tumours. Glutamine and glutamate can be major energy substrates for cancer growth (3). Glutamate is also involved in cancer signalling and there are glutamate receptors on cancer cells. Glutamine is abundant in the human body and converts to glutamate via the enzyme glutaminase, which can be, in part, blocked by Lycopene.

iii) High blood fat consumption levels can risk helping the spread of cancer, if the patient is not completely in ketosis. Being in ketosis is rather like being pregnant. You either are or you are not. I would say that 19 out of every 20 patients using a Keto Diet for cancer that I see in the UK, are not in Ketosis. We don’t have the Integrative doctors and few patients do the daily testing routines required. One patient I saw had a Cambridge University science background but openly admitted she was ‘not completely’ in ketosis. Her blood fats were 6.2, perfect for helping to spread her cancer (4).

iv) Restricting soluble fibre carbs can impair the microbiome, the immune response and the anti-estradiol response. In fact, a high fat, low carb Keto Diet alters the microbiome make up very quickly(5). In a small study on men who were obese, there seemed to be a diminution in inflammation markers, which is good news for autoimmune diseases. But lowered levels of commensal bacteria such as the Bifidobacterium family were also noted. And beware the type of fats you use. A systematic review where saturated fat was used for the Ketogenic diet showed negative effects on the gut microbiota (6).

v) There are also significant concerns regarding the safety and long-term effects of sustained ketosis in cancer patients. For example, a high fat, low carbohydrate diet produces ketone bodies by mimicking starvation. Fasting (for example with chemotherapy) is used for just 3-4 days, but Keto diets are used for months. A Ketone-rich diet is a proven weight loss programme (7). A sustained Ketogenic Diet might not be appropriate for many cancer patients because their cancer has already caused serious weight loss.

vi) Does a Ketogenic Diet improve survival times in cancer patients? Not really, according to a 2021 meta-analysis by researchers in Germany (8). There are a good number of in vitro studies, but few randomized clinical trials. And where there are results they are not favourable.  For example, a 2020 6-month study on prostate cancer failed to show any increased survival (9). Perhaps the trial was too short? In another meta-analysis, patients with breast cancer on a Keto Diet were reported as having a lowered overall survival(10), Of the 13 studies reviewed only four had improvements in overall survival.

The Keto Diet – what is it?

The Ketogenic Diet is a low carb, high fat diet to most advocates, and known to help lose weight and minimize inflammation in the body. It uses the Warburg Effect and is popular to the point of being a great fad, with tens of thousands of people using it.

But, it has also become a major question for cancer patients: “Should I be using a Ketogenic Diet”. 

Professor Thomas Seyfried of Boston College is a scientist of some note and a lovely and sincere man. He is the author of the Book, “Cancer as a Metabolic Disease”.  A few years back he was publicly saying that a Keto Diet could help you cure cancer, but in a recent video, I noticed a subtle change to ‘extending your survival time’.

The suggestion from ‘health experts’ in the USA is that a Keto Diet is Humans’ natural diet. I’m pretty sure that is simply not correct.

If you use the Keto Diet the way Seyfried wants you to use it, you would consume just 2% of your calories from Carbohydrate, 8% of your calories from Protein (including animal protein) and 90% of your calories from Fat.

When we lived in caves, there’s rather a lot of evidence that we dug up tubers, gorged on a the fruits of a cherry tree or ate the occasional animal that we hunted. I’m not sure Seyfried’s figures hold up.

The logic and the science of the Keto Diet

The theory behind the Keto Diet is that all cells burn glucose. However, while healthy cells are flexible and can burn alternatives like fats, proteins and ketone bodies formed from fat (in a process called ketosis), cancer cells are inflexible and derive their energy from a fermentation process which uses glucose as the primary fuel. Cancer cells need sugar. Cut the carbs and you will starve cancer.

However, if glucose were the only issue then you could use an Atkin’s diet. Do you remember that? It is where you avoided all carbs and ate lots of meat. And you lost weight. It was supposedly healthy. Some people have seen great improvements in the treatment programme for brain tumours with the Atkin’s Diet.

And this is where a lot of this focus lies – with brain cancer – and especially GBM. We know the brain is poisoned by glucose. Children can have 20+ fits (seizures) a day; but if you severely reduce their glucose consumption, the number of fits can fall to one or two a day, maximum. The keto diet has been a major breakthrough in the management of seizures. After all, it cuts your blood sugar. There is even a range of products called KetoCal to help you.

Cuts your blood sugar? According to Seyfried, the target for fasting blood sugar to get into ketosis is lower than 4.0 mmol/L.

But it is currently an inexact science. Other exponents of the Keto Diet, don’t think the 2-8-90 rule is applicable and believe you can go into a state of Ketosis at 70% fat.

Carbohydrate restriction in a Keto Diet

There are a couple of problems here.

  1. In cancer – especially oestrogen driven cancers like endometrial, breast, prostate and ovarian, phytoestrogens can compete for receptor sites with nasty estradiol and xenostrogen from herbicides and pesticides. But the best source – pulses like lentils, red kidney beans and other legumes – are not allowed on the strict Keto Diet.  How can we protect these patients with their estrogen driven cancers?
  2. For anybody, the best way to boost your immune system is to eat good quantities of soluble fibre. Your commensal bacteria love it – and the more of those there are, the stronger your immune response and immune memory. Soluble fibre? Oats, pulses, vegetables, nuts and seeds. Not allowed either in the Seyfried Keto Diet.
  3. One of the best ways of boosting your friendly bacteria is to eat berries. Blueberries, raspberries, cranberries, strawberries, blackberries. Walnuts too. From these you take ellagitannins into your system. These attack viruses, cancer cells and boost your commensal bacteria twice as much as pectins and inulin. Berries? Ellagitannins also break down into Urolithin A which has huge health and longevity benefits. Berries and walnuts? Not allowed on a Seyfried Keto diet.

Fat Consumption and a Keto Diet

There are a couple of problems here too.

4. There’s a general view amongst US ‘health experts’ that any fat goes – not just healthy unsaturated fat, but saturated fat too. Any fat helps form ketone bodies. But in cancer patients, the last thing you want is high blood fats – especially saturated fat and triglycerides. It’s OK with a brain tumour as it cannot metastasise outside of the brain, but other cancers? Breast cancer survival increases if a woman uses a low fat diet; smokers get higher rates of lung cancer if they have higher blood fats. There is even research showing that people with high blood fats get more metastases and survive least. Professor Olivier Feron, at Louvain Medical School in Belgium has recently shown that cancer cells ‘load up’ on fat and this feeds their journey around the body. High saturated fat causes cancer spread. High saturated fat damages your microbiome. Seyfried agreed. He, just as I, want at least 80 per cent of your fat consumption to come from good fat if you have cancer – extra virgin olive oil, oily fish and fish oils, avocado.

5. But saturated fat like dairy, nah. And then there is coconut oil. When I asked Seyfried if he would eat it, put it on his food, cook with it; he said “Nooo. It’s highly inflammatory”. He’s right, I agree. The research shows your gut bacteria make TMA from it, and your liver turns it in to TMAO, which is hugely inflammatory. And as for the usual comments about olive oil going rancid if you cook with it – just look at the American Food Standards Agency and find ‘flash points’ – top avocado oil, 6th olive oil, 22nd coconut oil. Yup, of the three, coconut oil burns first!

Protein restriction in a Keto Diet

It is with the attempts at protein restriction that the biggest problems occur.

6. Glutamine, an amino acid, broken down by enzymes into glutamate, can be an alternative energy source for cancer cells and many cancers. And, while several cancers seem particularly ´responsive´ to glucose, for example, brain tumours and colorectal cancers, others are especially responsive to glutamate, for example prostate cancer – there is a straight line relationship between blood glutamate levels and a man’s Gleason score.

It is particularly worrying that some people with both gut problems and cancer are recommended beef bone broth by their nutritionist. Beef bone broth is full of glutamine/glutamate.  So Seyfried wants me to restrict my animal protein – and therefore glutamine – consumption. Really? Is that going to starve my cancer? As I sit here writing this I AM FULL OF GLUTAMINE. It is in all my muscles, and 25% of my total reserves is in my brain. If I have a cancer cell and it cannot find glucose, it will just rob the adjacent cells of their glutamine. How could you restrict my glutamine by restricting my protein consumption. To this argument, Seyfried said “Well Chris. I admit we still have a few flaws to iron out in the Ketogenic diet. A ‘Flaw’? It’s the Grand Canyon of Flaws!

7. And to compound it, as any 16 year old Biology school children know, glutamine is a non-essential amino acid. You don’t need to eat it. You make it for yourself in your body.

A Keto diet with chemo- and radiotherapy

8. A Ketogenic diet sensitises murine pancreatic cancer tumors to cytotoxic chemotherapy (11). The same research showed that a Keto diet did not help on its own. While the ketogenic diet decreases glucose’s concentration and tricarboxylic acid cycle contribution, it also elevated NADH and did not impact tumor growth. By contrast, using simultaneous chemo raised NADH significantly and inhibited tumour growth.

9. Both a Ketogenic Diet and Fasting for 3-4 days over chemotherapy (because it brings on Ketosis) have been shown to reduce toxicity to healthy cells (12). At CANCERactive, except when patients have weight loss issues, we have recommend a fast to improve chemo effectiveness and reduce toxicity for more than 15  years now.

10. In an Iowa University study (13) researchers concluded that there was an overall survival gain for patients with NSCLC and pancreatic cancer using a Keto Diet whilst having radiotherapy. But, please excuse me for laughing, while Xenograft experiments with mice demonstrated prolonged survival, the clinical trial with humans seemed to fall apart. Of the 7 patients with NSCLC, only two completed the trial; and it was just one of two with pancreatic cancer. The rest fell by the wayside – the diet was too arduous and in two cases actually caused toxicity.

Should cancer patients employ a Ketogenic Diet?

My personal conclusion is that the Keto diet in cancer is a contrived diet that is not all it’s claimed to be.

No ancient tribes walked around eating few carbs, little protein and pouring fat down their throats – they ate nourishing whole foods, carbohydrates, nuts and seeds; they ate fresh foods – vegetables and fruits – and stored fruits – dates and preserves. And olive oil. They ate whatever they came across or caught – fish, and chicken and goat.

And that’s the Rainbow diet – the colourful Mediterranean Diet – its ingredients protect and correct. We have 95 research studies on this Website – with humans, who for over 5,000 years have eaten and thrived on the diet. There are more 80, 90 and 100 year olds in the ‘Blue Zone of Sardinia than anywhere else in the World. It is what it is, and what it has always been: probably the Healthiest Diet in the World.

The Keto diet to starve and cure cancer? Cancer, in the vast majority of cases, is definitely a metabolic disease. Christine Meyer of Sloane Kettering has proven that there are no new mutations in your DNA; it’s your message system that has been blocked or damaged in the microenvironment of the cells.

The problem in cancer is that the Warburg effect is not the only driver. It’s hard work and not an enjoyable diet.  People over claim its benefits. Two people I know who beat their GBMs were not actually on a Seyfried style Keto diet, despite their claims – they were on an Atkins diet and eating a lot of meat.

The Keto Diet might possibly increase survival times a little by slowing cancer down for a short while, (note ‘possibly’ and ‘might’) but overall I think survival depends on which cancer you have, how far it has progressed and what else you are doing. And the Keto Diet seems too restrictive for the vast majority of patients, with little reward and not without a few risks.

Go to:  More on the Ketogenic Diet and cancer

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References

  1. Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress; De Huang, Tingting Li, et al; Cell Research volume 26, pages 1112–1130 (2016)
  2. Ketogenic Diet and Breast Cancer: Recent Findings and Therapeutic Approaches; Alfio Giuseppe Urzì et al; Nutrients
    . 2023 Oct 13;15(20):4357.
  3. Glutamate in cancers: from metabolism to signaling; Haowei Yi et al; J Biomed Res. 2020 Jul; 34(4): 260–270.
  4. How high blood fats spread cancerhttps://www.canceractive.com/article/saturated-fat-and-increased-cancer-risk
  5. Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells; Qi Yan And et al; Cell, vol 181,  6, p1263-1275; JUNE 11, 2020, 
  6. Dietary fat, the gut microbiota, and metabolic health—A systematic review conducted within the mynewgut project; Wolters M., et al; Clin. Nutr. 2018
  7. Ketogenic diet in the treatment of cancer – where do we stand? Weber DD, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger RG, Kofler B. Mol Metab. 2020;33:102–121
  8. The use of ketogenic diets in cancer patients: a systematic review; Maximilian Römer,corresponding author Jennifer Dörfler, and Jutta Huebner; Clin Exp Med. 2021; 21(4): 501–536.
  9. A randomized controlled trial of a 6-month low-carbohydrate intervention on disease progression in men with recurrent prostate cancer: carbohydrate and prostate study 2 (CAPS2); Freedland SJ, Allen J, Jarman A, et al; Clin Cancer Res. 2020;26(12):3035–3043
  10. Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes. Klement R, Brehm N, Sweeney R; Med Oncol. 2020;37:14
  11. Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth; Lifeng Yang et al; Med, 2022 Feb 11;3(2):119-136
  12. Diet and Chemotherapy: The Effects of Fasting and Ketogenic Diet on Cancer Treatment; Francesco Plotti et al; Chemotherapy; 2020;65(3-4):77-84.
  13. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung and Pancreatic Cancer; Amir Sahra et al; Radiat Res. 2017 Jun; 187(6): 743–754.

 

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