A Ketogenic Diet as an Effective Cancer Treatment?

Yesterday, my mother (not a rationalist) told me that she had recently heard somewhere (most likely on a popular television program) that, as simple as it sounds, an effective cancer treatment is cutting back on glucose intake. According to her story, cancer cells can only efficiently use glucose as fuel, and will be unable to multiply (or will starve, or something like that) if you don't consume any. Meanwhile, normal cells can convert other forms of energy into glucose inside their membranes, and then will continue functioning normally.

My first two thoughts:

Reality just can't be that nice.

Hey, wait a second, doesn't the body just convert everything into glucose before it's released into the bloodstream, anyways?

So I did some Googling and I found out that what my mother was referring to is called a ketogenic diet (from Wikipedia):

The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fuelling brain function. However, if there is very little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures.

So, prima facie, my second objection was dealt with. More Googling led me to discover these two references to what my mother had mentioned:

According to the paper:

Abnormal energy metabolism is a consistent feature of most tumor cells across all tissue types [14]. In the 1930 s, Otto Warburg observed that all cancers expressed high rates of fermentation in the presence of oxygen [15]. This feature, known as The Warburg Effect, is linked to mitochondrial dysfunction and genetic mutations within the cancer cell [14], [16], [17]. These defects cause cancers to rely heavily on glucose for energy, a quality that underlies the use of fluorodeoxyglucose-PET scans as an important diagnostic tool for oncologists [18]. Ketogenic diets are high fat, low carbohydrate diets that have been used for decades to treat patients with refractory epilepsy [19]. Ketogenic diets also suppress appetite naturally thus producing some body weight loss [19], [20], [21], [22]. Dietary energy reduction (DER) lowers blood glucose levels, limiting the energy supply to cancer cells, while elevating circulating blood ketone levels [6]. Ketone bodies can serve as an alternative energy source for those cells with normal mitochondrial function [23], [24], but not for cancer cells [25]. DER has been shown to have anti-tumor effects in a variety of cancers, including brain, prostate, mammary, pancreas, lung, gastric, and colon [14], [26], [27], [28], [29], [30], [31], [32], [33], [34]. DER produces anti-cancer effects through several metabolic pathways, including inhibition of the IGF-1/PI3K/Akt/HIF-1α pathway which is used by cancer cells to promote proliferation and angiogenesis and inhibit apoptosis [35], [36], [37], [38], [39], [40], [41], [42]. Additionally, DER induces apoptosis in astrocytoma cells, while protecting normal brain cells from death through activation of adenosine monophosphate kinase (AMPK) [43].

Note what the sentence with ten citations says. Why have I never heard of this? If the basic claims being made are true, we seem to have an effective way of at least preventing cancer from progressing further (if not killing it off), and it's not even dangerous (at least compared to the alternatives, as far as I am aware of...however, I realize I know next to nothing in this field...that's the reason for this post)! Is there some reason this isn't being sung about on Reddit as a huge victory for science? What is the counterevidence? Or are we still waiting for more research to be done?

For genetic reasons and because humans often engage in motivated reasoning, I am skeptical. I am querying the Less Wrong community for more information...perhaps some of you have already heard of a ketogenic diet being used as a cancer treatment, or would like to do more research than I've done now that I've introduced you to it. The following books may also serve as helpful, albeit expensive, references:

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Many of those references don't support the claim or only support it very weakly. For example, one of the articles in the long list of citations is this one, and says:

None of the LI changes observed between and within the three arms of the trial were found to be statistically significant. Thus we failed to prove that glucose consistently stimulates or lipids inhibit tumour proliferation despite a trend in this sense.

So the data isn't quite that strong. Some of the other bits above are a little weaker than one would hope for:

Ketone bodies can serve as an alternative energy source for those cells with normal mitochondrial function [23], [24], but not for cancer cells [25].

But the reference for 25 is only for brain tumors in certain limited contexts in children.

Overall, this is an interesting area of ongoing work, but it isn't nearly as universal as you might think. There are also other issues involved: people with late stage cancers often have enough trouble eating as is (a large fraction actually die of starvation), and getting them to eat anything is an accomplishment. So at that level, for a lot of post-metastasis patients, this will be happening naturally anyways.

people with late stage cancers often have enough trouble eating as is (a large fraction actually die of starvation), and getting them to eat anything is an accomplishment. So at that level, for a lot of post-metastasis patients, this will be happening naturally anyways.

Starvation does not equal ketosis. If cancer patients are suffering from nausea and lack of motivation to eat anything, they and their carers may not select high fat low carbohydrate foods that would promote and sustain ketosis and may instead choose simple and easy to digest carbohydrates and sugary treats.

(Your comment upvoted.)

I'm sort of surprised you haven't heard of this and it is being sung about on Reddit.

Dietary science is a mess but I would definitely say that the evidence currently favors something like the ketogenic diet (which closely resembles Paleo and past-decade trends like Atkins and South Beach.) Part of the problem is that this squarely contradicts what the medical community has advised for the past fifty years (eat more carbs, less fat!). It is difficult to overcome a) the education of older medical professionals and b) what people have been told in school and on the back of cereal boxes for decades.

There also definitely isn't enough data, especially on humans (or anything that isn't a very cancer prone rat).

Gary Taube's Good Calories, Bad Calories and Why We Get Fat are other standard references.

My understanding of the issue is that different cancers are different. Sometimes radically different. Certain specific types of cancers have been shown to react well to ketosis. Others have been shown to be indifferent to it.

I agree that the current state of the medical science on what humans eat and how does it affect them is an incredible mess. Try Ioannidis for starters, or a popular article about basically the same thing.

At this point my prior about medical news in the press (e.g. Google News) is that it's wrong and my prior about most papers on PubMed and such is that they claim far more than they can prove. There are massive biases all around together with money (and government) exerting an active influence on what people should believe.

Repeat after me: "Cancer is not a single disease, and mice are not humans".

So this is true, and these are both points that are often missed when discussing these issues. But at the same time, it is worth noting that A) a variety of the studies listed were with people rather than animal models and B) while cancer is better thought of as a collection of distinct diseases, that doesn't stop there from being treatments that work for a large variety of different cancers. For instance, many forms of chemotherapy target cells which are dividing, which since that's a common property of cancers, often manages to hit on a large number of cancer types. Similarly, we can classify cancers in some detail, and large classes of cancers often have the same or similar properties.

Why isn't Reddit singing? Several possible reasons:

  1. Most published research findings are false. - this sort of problem makes people wary of new research.

  2. Preventing and curing diseases is bad for business if you're in the medical industry. However, average people look to doctors to tell them what's real and what's not. It may be that doctors aren't spreading the word very fast, or are downplaying the message because of perverse incentives.

  3. They may be prone to overconfident pessimism.

and it's not even dangerous (at least compared to the alternatives, as far as I am aware of

Actually, I've heard that low-carb diets are criticized for increasing the risk of colon cancer, however the problem (from what I, a non medical professional understand) might have been too little fiber (which you can just add to your diet...).

Also, there's a state called "Atkin's attitude" which basically means your blood sugar can get too low making you really grouchy (hazardous socially, obviously).

Also, a low-carb diet can throw off your ph balance, evidently. I am on a low-carb paleo diet and was told by a doctor to use a teaspoon of apple cider vinegar daily to stop the joint aches I was having that were caused by ph imbalance.

Doing anything with your health is going to be complicated and might be tricky. It's good to get as much knowledge as possible.

I do a high fat, intermittent fasting, paleo diet in which I'm often in ketosis in part to reduce my cancer risk.

This book is a great resource: The Perfect Health Diet

Does that book reference any additional studies not mentioned in notsonewuser's post or otherwise contain more evidence pertaining to the relationship (or non-relationship) between ketogenic diets and cancer risk?

You can browse the Perfect Health Diet website -- there is a LOT of information right there including tons of citations, a useful blog, and somewhat useful forums. The website should be enough to allow you to decide whether it makes sense for you to dive into the book or not.

It has a huge number of citations, but I'm not sure if any meet your criteria. The book has lots of theory on the costs and benefits of a ketogenic diet.

For those who can't get the book, here's a free full-text review by Dr. Seyfried:

Targeting energy metabolism in brain cancer: review and hypothesis


This is strictly pop-science writing, but there was an interesting piece in the NYT Magazine a couple of years ago about ketosis as a treatment for pediatric epilepsy, where apparently it's extremely effective at controlling seizures in a significant fraction of patients.

Ketosis is the traditional treatment for pediatric epilepsy going back to 1920s or so. The diet is based on eating, erm, drinking heavy cream -- lots and lots of it and little else. It helps with the epilepsy and doesn't seem to have major effects on health otherwise (which confuses/annoys great many dieticians). The main problem with the diet is its monotony and getting the kids to stick with it.

There was some TED talk on cancer, and how cancer seldom spreads in muscle tissue. It can go there, but seldom grows when it gets there. I wondered if weight training while you have a metastasizing cancer would allow the muscle to act as a cancer filter for the rest of the body.