Ketogenic Diets for Cancer

[gdpawel]

Dr. Georgia Ede slogged through Dr. Thomas Seyfried's new book entitled "Cancer as a Metabolic Disease," which convinced her that cancer is not caused by genetic mutations. His summary of the research makes it clear that mutations are caused by cancer, not the other way around. She says that the very fact that so many (hundreds of thousands) different types of (unique) mutations are (loosely and unreliably) associated with cancer is just one clue that we have been barking up the wrong (and most expensive) tree. Dr. Seyfried proposes that cancer is a mitochondrial disease, not a nuclear (DNA-based) disease.

Mitochondria are the cell's power generators, and when they become damaged (by radiation, poor diet, viruses, chemicals, etc), the cell has to resort to a primitive process of energy production (fermentation) which is wasteful and messy and (long story short) damages DNA. The upshot of the book is that cancer is best treated using a metabolic (i.e. nutritional) approach that reduces mitochondrial stress--ketogenic diets. Ketogenic diets are specially formulated diets that force the body to burn fat instead of glucose for energy. His work gives people with cancer (and those who want to prevent cancer) real hope.

She says the book is a tough read, but for anyone who is curious, she wrote a series of 4 short blog posts that attempt to summarize his incredibly important work in plain (and hopefully entertaining) English. The book left a lot of questions about ketogenic diets and she has information about Ketogenic Diets for Cancer and Beyond.

http://diagnosisdiet.com/ketogenic-d...er-and-beyond/
http://diagnosisdiet.com/what-causes-cancer/
http://diagnosisdiet.com/what-causes-cancer-part-ii/
http://diagnosisdiet.com/dietary-treatment-of-cancer/
http://diagnosisdiet.com/cancer-hope/

[gdpawel]

In regards to the ketosis diet issue, for the first time ever, a randomized controlled trial that uses calorie restriction as a treatment for cancer, and measures a cancer-related outcome, was approved by the institutional review board at Duke University. Stephen Freedland, M.D. from Duke told Medscape Medical News that in the entire field of cancer research, there have only been a handful of studies of calorie restriction as a cancer treatment. But none of them were randomized clinical trials.

http://www.medscape.com/viewarticle/778613

The hardest of all diet intervention studies have to be dietary intervention studies to reduce cancer. A study published in the Journal of the National Cancer Institute showed that women with estrogen receptor negative breast cancer cut their recurrence rate by 60% if they stayed with a diet in which fewer than 20% of calories were from fat.

Nothing has ever achieved results like this before. Not chemotherapy, not radiotherapy. If results like this were ever obtained by a new drug, it would be the breast cancer treatment breakthrough of the decade.

You can debate all you want, but if you are diagnosed with breast cancer and it turns out to be estrogen receptor negative, you can either wait for proof beyond reasonable doubt or you can go with the preponderance of evidence, which is that you can cut your chance of having cancer come back 60% if you cut the fat in your diet by 30%.

Chlebowski, R. et al. Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study J Natl Cancer Inst, Dec 2006; 98: 1767 - 1776.

William Li: Can we eat to starve cancer?

http://www.ted.com/talks/william_li.html

Evidence from research on epigenetics suggests that the epigenome can be influenced by the environment which means epigenetic modifications that lead to carcinogenesis may be reversible by changing the environment.

And that envirnomental change is the totality of surrounding conditions - the milieu of the cell (toxins, viruses, carcinogens, diet). Detoxification (removing toxins, viruses, carcinogens and other biological contaminants) followed by improving what a patient consumes (organic, whole, vegetarian foods, vitamin supplements, etc.), the creation of a healthy milieu.

[Mandamoo]

Thank you for this post - I have been reading about this for a few weeks now and find it very interesting. What I am a little confused about is that ketogenic diets focus on fat being about 80% of your calories which seems to contradict the other study cited. I understand the Role of insulin and can see how when you look at the entire population of people with breast cancer the are a significant proportion that are overweight and may already have existing metabolic disorders and issues but what about younger, fitter women of normal weight - how does it work here? I have been making changes in the past few weeks to follow mor of the diet recommended here - already I have lost 4kg and that is not really my aim as I am not overweight. I am continuing to read and find this very interesting.
In this study (which may be the on above but I can't read it) http://www.nutritionandmetabolism.com/content/8/1/54 even though it is a small sample I thought the results impressive.
It seems most of the data relates to brain disease and cancer - would love to see more on other cancers.

[gdpawel]

I understand the contradiction. Like I stated, the hardest of all diet intervention studies have to be dietary intervention studies to reduce cancer. Dr. Klement said be it through physical exercise, ketogenic diets, fasting, or calorie restriction, the time is definitely ripe to test the various ways of altering cancer patients' metabolism.

A drug that originally was used to treat breast cancer has been helping combat the severe weight loss that can plague patients undergoing cancer treatment. The drug reduces weight loss and can improve the quality of life in patients. Megace (megestrol acetate) was found to induce weight gain.

The drug's effectiveness was as an appetite stimulant for patients with HIV, chronic diseases and cancer cachexia, a "wasting syndrome" in which fat and muscle are lost because of the presence of a cancerous tumor.

According to Dr. Michael Farmer, one of the researchers studying Megace, it is critical to maintain adequate food intake and hydration, yet one of the most frequent complaints from patients during therapy is a decreased appetite.

Weight loss is correlated with decreased overall survival, decreased quality of life and decreased response to treatment. In addition, if the weight loss is severe enough, it can lead to breaks in treatment that may decrease the effectiveness of therapy. This was predominately with lung and head and neck cancer.

My wife was given Megace to help increase her appetite. Our pharmacist told us it had about a 50/50 chance of working. We took the chance, and it worked, over time. Within about three months, she gain back about 2/3rds of all the weight she lost.

[StephN]

Being estrogen recepter negative, this is interesting to me.

I would like to know whether the diet should have 20% or less calories from fat or 80% of the calories. That is a HUGE discrepancy, and seems to invalidate the whole idea, unless there is a reasonable explanation.

Although the study cited used the 20% figure.

In my case, I have been able to cut the fat from my diet to probably an average of 20 % or less many years back. I don't count calories, but eat mostly fresh and lean. I also don't normally eat very big meals or snack very much.

Who knows, this may be another reason my cancer stays at bay???

[Mandamoo]

Steph - my reading of above is that we are referring to two differing suggestions.
A study published last week about women with hormone negative disease reducing their fat intake by 20% having reduced rate of recurrence.

The other is in relation to using ketogenic diets to starve cancer,
"Dr. Seyfried recommends a specially-formulated low-calorie “ketogenic” diet consisting of 80% fat, with the rest (20%) being made up of protein + carbohydrate." so the two suggestions are polar opposite really. unless you reduce your caloric intake so much that 20% less is 80% of your intake!

I have been looking more at the paleo style diet which reduces carbohydrates from refined sources considerably - it is a no grains diet and a no dairy - it seems to tie in nicely but the ketogenic diet is more extreme. I think there is a lot to be said, the more I read about eliminating grains from diet - both from an inflammatory point of view and a carbs fuelling cancer perspective. I think we all vary enormously in how our bodies respond to food just as we do with medications so it is likely that one diet does not suit all. I personally wonder if the reduction of 20% in fat intake corresponds with weightloss which impacts insulin resistance issues for many women thereby assisting in reducing recurrence.
If only it were clear!
A x

[gdpawel]

I'm rusty on this, but I think if you stayed with a diet in which fewer than 20% of calories were from fat. In other words, lower your dietary fat to less than 20% of total calories by emphasizing vegetables, fruits, low fat dairy, controlled portions of healthy-type meats, etc.

[AlaskaAngel]

The discussion is very interesting when considered together with many of RB's posts.

It seems to me that by lumping all types of fats together as if the percentage of the diet that is fats is the only important factor, we may be missing a less obvious factor. The chemistry of the type of fat consumed may make a difference.

That usually results in getting side-tracked into a tug of war over the issue of whether it is more ethical to be vegetarian or not. But if one can skip past that discussion and examine the actual chemistry of the metabolism of fats, do vegetable-based fats tend to form different bonds than meat-based fats do, and in the process of metabolism, does one type of fat tend to bond more easily with toxic or cancer-causing substances, causing them to be retained in the body?

A.A.

[R.B.]

^ Hi AA (-:

Totally (-:

Different fats are metabolized very differently and have very different functional effects in the body.

I would argue the type of fat in the diet / looked at in trials is of enormous importance, and is probably the explanation for such varied results in dietary trials.

The utilization of fats by the body is a massive and complex subject.

For those interested in the subject of fats I would suggest inter alia a quick skim of my Omega 3 : 6 post below.

I will try and add some more thoughts in the next few days

[TanyaRD]

RB and AA, I agree that the type of fat appears to be of utmost importance. The is plenty of evidence to suggest saturated fat increases breast cancer risk. The diet being referred to (20% calories from fat) is the WINS trial. While the women in this trial did not follow a totally vegetarian diet most of their fat was of the monounsaturated type.

[R.B.]

(I am still editing this at the moment adding links etc)



Thanks all for the interesting and thought provoking links which I am still working my way through.


The body is mindbogglingly complex, as are the ways that nutrients are metabolised and used, which is an important but not particularly helpful statement.

It appears accepted that cancers are greedy consumers of energy, and a little like racing cars stall if run on idle, where as normal cars and normal cells idle quite happily if fuel delivery is low.

But the often made suggestion that cancers will only run on glucose is a vast oversimplification and based on this paper a bit of a myth.http://www98.griffith.edu.au/dspace/...4244_1.pdf?seq The reality appears to be that cancer is amazingly adaptable and if needs be dependent of course on type will burn anything in sight that is capable of being turned into fuel including fat and protein, on which basis it is not a simple as restricting glucose / fructose http://her2support.org/vbulletin/showthread.php?t=54709 / ketosis.

However there is growing evidence that certain fats will reduce the risk of cancer development and progression, and others increase that risk.

Cancers also dont seem to like ketones much

http://high-fat-nutrition.blogspot.c...d-ketones.html
http://www.thebarrow.org/Research/Neuro_Oncology/213930

As above the body utilities fats in many ways including as part of the machinery of the production of energy, cellular structure, signalling mechanisms.

Different fats are used in very different ways.

There are only two fats the body cannot make Omega 3 and 6, all other fats can be made in the body by elongation, adding double bonds or dissembling them to shorter fats.

The body cannot make short chain fats but they are made by bacteria by fermentation of simple (carbs) and complex starches (fibre) in the gut, depending on gut health the appropriate bacteria being present and happy with the environment, provided with the necessary fibre as fuel etc .

The fact the body can make most fats and does raises interesting questions as to the current paradigm that saturated fats are inherently harmful; the reality is it is just not simple - in the right proportions saturated fats are essential.

Omega 3 and 6 have particular significance because we cannot make them from scratch.

There is for me significant evidence that excess dietary Omega 6 increases the risk of cancers and Omega 3 reduces it. Budwig reported having positive results against cancer using flax seed. The explanation of the science is of its time ! but apparently Johanna was nominated several times for a Nobel prize, and was well respected; unfortunately we cannot turn back time to look at the evidence of the effect of her treatment using flax and cottage cheese ourselves.

There is also a highly thought provoking paper on an elderly man with lung tumors that were greatly reduced when he moved onto a high Omega 3 low omega 6 diet without cancer treatment, and had his doctors follow his health / the cancer with regular scans etc. There are lots of reason why Omega 3s may help reduce inflammation and affect mitochondrial function, including as to why it would effect mitochondrial energy production and cell death. http://her2support.org/vbulletin/showthread.php?t=42280

Also an elderly female patient with a brain tumour on a partial ketogenic diet plus cancer treatment chemo etc unusually achieved regression in 2-2.5 months (scans suggested the tumour had completely regressed); tumour growth restarted when the diet was stopped (see Lucas Tafur link below and referred to above) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874558/

There are also a number of reports that short chain fats and fats produced by bacteria in the gut by fermenting carbohydrates such as butyrate may reduce the activity of cancer cells (the mechanism is likely to be 'indirect' rather than by simple energy restriction http://jn.nutrition.org/content/133/7/2485S.full ). The butyrate and other fats produced appear to be used mainly by the gut and liver but a small amount may enter the circulation.

Fermented foods also contain the same short chain fats as well as the bacteria. If the simple starches in the these foods have already been converted to fats they will not be available to convert to glucose. Fermented food have long been associated with health benefits. A healthy gut flora is essential to health, and gut flora activity is nutrient production is a much bigger issue than commonly realised.

There is also evidence that cancer cells are not overly fond of short to medium length fats, and there is some suggest that Medium Chain Triglycerides may reduce cancer viability. MCT are essentially fats below 12 carbons long, so include lauric acid one of the fats in coconut oil.

Of course all of this is multi factorial and the body needs adequate nutrients to function properly, including vitamin D iodine, minerals, B vitamins etc. We can only usefully eat so much in a day. Each mouthful is a nutrient opportunity the question is how to use that opportunity in an optimal way, and will be different in the circumstances for each individual.

It is certain that refined foods, sugars, oils etc are not a best use of our limited opportunities to refuel; and depressingly the whole land based food chain is becoming increasingly depleted of nutrients for a variety of reasons, which means looking to marine foods and for the highest nutrient rich foods we can find.

In summary ketogenic diets may have a role, but the only suggestions I have seen as to ketogenic diets decreasing cancer cell viability included either and Omega 3s and or MCTs - and strict medical ketogenic diets have their own nutritional issues and people often find them difficult to tolerate. A strict medical type ketogenic diet would exacerbate the problem of optimising nutrient intake in a world where our lifestyle and food make getting a nutrient dense diet very difficult.

Having said that a healthy 'ketogenic light' diet which keeps calorie intake on the low side e.g. not more than the body reasonably needs, which keeps blood sugars down, by avoiding carbs including high carbohydrate fruits, as suggested in this paper http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157418/and further usefully explained by Lucas Tafur in his blog http://www.lucastafur.com/2011/08/ad...c-diet_10.html woould seem to make sense.

It is pretty close to what I generally eat anyway. Fermented food should be low in simple sugars, so may be a way of getting carb type foods but without the down sides. I have tried to find papers quantifying the effects of fermentation of grains of various types on their sugar content without much luck, but my fermented oats certainly taste quite sharp. Non western traditional cultures historically used a vast range of fermented foods

So maybe things to look at would include the inclusion of fermented foods, kefir saurkraut yogurt cottage cheese fermenting oats, omega 3s as flax, fish oil, mineral and iodine rich foods, plus other nutrient dense foods. The fermented foods as well as being predigested, and lower in sugars, will likely will improve gut health by providing hopefully friendly bacteria short fats etc. Gut health connects into immune function - improved gut health = improved immune functions . . . less inflammation etc.

MCTs are used by sports people and available as a dietary product. Coconut contains significant amounts of lauric acid a medium chain fat. Short fats are reported to assist immune function, act as antibacterials etc. They are also more easily available to the mitochondria. There are suggestions lauric acid may reduce cancer cell viability, but as usual much is not known.

Vegetable juices are low - lowish in sugars, contain fiber and are nutrient dense - brassicas are goitregenic viz iodine blockers so would arguably increase the need for iodine.

Apparently Budwig recommended flax cottage cheese and sunshine, and was very highly regarded by a large patient base - Flax contains Omega 3s, cottage cheese contains good bacteria, + short fats from fermented milk sugars whey is a good source of proteins, diary contains iodine http://her2support.org/vbulletin/showthread.php?t=53928 etc. ) ; sunshine gives lots of vitamin D http://her2support.org/vbulletin/showthread.php?t=43711 which would all logically be beneficial to overall health; science has caught up with Budwig's foresight largely based I suggest on her single-minded bravely independent observation intuition and vision, as her attempts to explain her observations in then science and do not at the detailed level make much sense in the light of today's knowledge, but the direction of thought is clear and prescient - but it appears from today's science Budwig was heading a good direction - clearly a woman much ahead of her time - I just wish it was possible to know more about her work and cancer patient outcomes; thought provoking stuff (-:

[Jackie07]

Exp Gerontol. 2013 Feb 20. pii: S0531-5565(13)00047-8. doi: 10.1016/j.exger.2013.02.016. [Epub ahead of print]
Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay cancer progression.

Brandhorst S, Wei M, Hwang S, Morgan TE, Longo VD.
Source

Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.

Abstract

Short-term starvation (STS) protects normal cells while simultaneously sensitizing malignant cells to high-dose chemotherapeutic drugs in mice and possibly patients. The fasting-dependent protection of normal cells and sensitization of malignant cells depends, in part, on reduced levels of insulin-like growth factor-1 (IGF-1) and glucose. Calorie restricted diets with defined macronutrient (carbohydrate, protein, fat) ratios were evaluated for the effects on stress sensitization markers and protection in mice treated with high-dose chemotherapy.

We show that short-term CR significantly reduced both glucose and IGF-1 levels, but when specific macronutrient deficiencies were tested, only the complete lack of proteins reduced IGF-1 levels. Short-term 50% CR combined with either severe protein-deficiency or ketogenic diets improved chemotoxicity resistance similarly to the standard 50% CR, but did not result in the high protection caused by STS.

Notably, a high protein diet reversed the beneficial effects of short-term CR. In a subcutaneous mouse model of glioma, feeding a low protein (4% calories from protein) diet for more than 20 days did not delay tumor progression once the tumor became palpable. Also, cycles of short-term (3 days) 50% CR did not augment the chemotherapy efficacy of cisplatin in a murine breast cancer model.

These results indicate that the protection from chemotoxicity and retardation of the progression of certain tumors achieved with fasting is not obtained with short-term calorie and/or macronutrient restriction.

[R.B.]

^ Thanks Jackie

I would really like to know the details of the diets the mice were fed on etc. Ketone production will be accompanied by the use of fats for fuel - the type of fats available from the fat tissue will be dependent on historic / current diet.

Fats are metabolised very differently.

The only papers I have seen suggesting ketones restrict cancers have involved Omega 3s or MCTs, so maybe the effects seen are about more about more than just the ketones, which makes sense for a host of reasons.

If anybody has seen any papers suggesting ketosis alone has reduced cancer growth I would be very pleased to see them . . . there are only so many hours in the day to google / search for data read papers, and there is so much fascinating material out there . . .

[ketojane]

I've been using a low carb diet sporadically for years to control Type II diabetes. After beginning the use of injected insulin, my plenteous weight quickly added 25 pounds more in a few months. So, I went on a serious ketogenic diet just before the last cancer diagnosis. Eventually, after hours of googling, I came across a ketogenic diet website which had a link to an ebook titled, "Fight Cancer with a Ketogenic Diet". There were a few things that had to be tweaked, but I was already accustomed to using coconut oil and olive oil with very little saturated fats, although animal fats are not favorites of mine except for butter. Anyway, I've cut out butter and cheese along with other milk products at least for now. We'll see what happens as I go along.