The Ketogenic Diet and Cancer

Ketogenic Diet > Keto Diet Information

With the increasing incidence of cancer in the general population, it is important for us to look beyond traditional cancer therapies towards nutritional & other therapies, not only as a measure to prevent cancer but also as an alternative to standard cancer therapies or an additional tool used in conjuction with those therapies.

One nutritional therapy that is picking up momentum both in the research and oncology communities is the ketogenic diet. While this is not a cure for all cancers, there are many cancers that are responsive to this dietary change.

Before we dive straight into why the ketogenic diet is increasingly being looked at as a primary or at least supportive treatment for cancer, let’s take a brief look at what cancer is so that we can get a better understanding of the role of a ketogenic diet & other nutritional therapies in preventing or treating cancer.

The Metabolic Link With Cancer

While there is not a scientific consensus on exactly what causes all cancers, there does seem to be common factors in cancers. Each of these factors or “hallmarks of cancer” has to do with the way a cancer cell seems to “go wrong” as compared to the way normal cells work [1].

  • Self sufficiency in growing signals
  • Insensitivity to grown inhibitory signals
  • Evasion of programmed cell death
  • Limitless replicative potential
  • Sustained vascularity
  • Tissue invasion & metastatis

In other words, a normal cell works with the rest of the body like a good, law abiding citizen. It gets its “growing signal” from the body as well as the signal to stop growing. It also dies when it’s given the signal to do so. The body is so good at giving those signals that the cell won’t grow beyond what it should and won’t reproduce uncontrollably. This keeps the cell exactly where it’s supposed to be in the body so that the body, as a whole, can work properly.

On the other hand, something goes wrong in the communication area of a cancer cell. It simply doesn’t respond as it should & this leads to be problems. The more it replicates, the more it needs the body to work for it – building new blood vessels to supply it with oxygen and fuel for it to continue growing. In other words, the cancer cells are sort of like tiny little terrorists inside our bodies – doing whatever they want & placing ever-increasing demands on our bodies.

This malfunction that turns a cell from a law abiding citizen to a terrorist is perplexing though. You see, mutations in the cells are extremely rare events. That means it’s extremely unlikely that the numerous mutations found in cancer cells (causing the hallmarks above) would occur sporadically during the course of a normal lifespan. This presents an interesting paradox. Cancers have those hallmarks in common but how is it even possible that cancer cells express so many different types & kinds of mutations?

While there doesn’t seem to be one gene or one specific mutation that is common to all cancers, nearly all cancers seem to exhibit what is called the “Warburg effect“. The Warburg effect is when a cell uses glucose along with oxygen for fuel while producing lactic acid (you know, that stuff that causes cramps & side stitches while you are working out) regardless of the tissue or cell origin of the cancer. This process is known as “aerobic glycolysis“.

The medical community has known about this for quite some time – in fact, one of the ways they get an image of a tumor is essentially by injecting a glucose based “dye” into the body and then using some sort of machine to see that “dye”. The area that lights up the most when taking the image is where the cancer tumor is – that’s because of the cancer cell’s LOVE of glucose as fuel.

But, wait a minute….don’t all cells use glucose as fuel?

The simple answer is: yes. However, while a cancer cell uses glucose in the presence of oxygen to produce lactic acid (which inflames the body), our normal cells only produce lactic acid in the absense of oxygen. This shows us that there is something going on here – the fuel producing ability of a cancer cell seems to come from damage to what we call the “respiratory capacity” of the cell. Warburg proposed, with considerable certainty after observing this, that irreversible damage to the respiration of a cell or tissue was the prime cause of cancer.

In other words, he saw cancer as a metabolic disease of the cell [2-4]. His theory was attacked quite fervently & his view was eventually replaced with the view of cancer as a genetic disease. However, knowing what we know about how rare a mutation is…there seems to be problems with that theory as well & research is starting to renew interest in the metabolic basis of cancer [5-8].

Nutritional Therapies in Prevention & Fighting Cancer

This is where the ketogenic diet comes in, along with a few other (somewhat relevant) nutritional therapies. Because one of the main features of a ketogenic diet with it’s high fat, low carb (with a focus on carbs from vegetable and/or dairy sources), and low to moderate protein basis is that it forces the cells in our body to use ketones (a by-product of the body breaking down fat) rather than glucose (a by-product of our body breaking down carbohydrates and excess protein) as its main energy source.

High Fat & Low Carb

So, while glucose is the primary fuel source for most cancer cells, a ketogenic diet – which is very low in the very food that the body turns to glucose – becomes a problem (for the cancer cells, that is).

Remember a few sentences ago when I said our cells have to switch to using ketones for energy rather than glucose when we are eating a ketogenic diet?

And, do you also recall how I mentioned that one of the theories around cancer is that the cell’s metabolism is kind of broken? Guess what that broken metabolism of a cancer cell can’t do? It can’t seem to make the switch from using glucose for energy to using ketones for energy – at least it can’t do it efficiently.

Additionally, there have been a few studies that claim to show a “reverse Warburg effect” – where a byproduct of ketones plus lactic acid is used to stimulate tumor growth [9]. While some people find these studies as “proof” that a ketogenic diet is not effective in killing cancer by starving it, that is not accurate at all. The problem with that conclusion, of course, is that these ketone bodies were introduced along with end-products of aerobic glycolysis – a process that wouldn’t happen if one were to severely restrict the intake of carbohydrates & deprive the body of enough glucose to actually go through the aerobic glycolysis cycle.

Therefore, those studies that show the “reverse Warburg effect” actually do not prove that a ketogenic diet would be ineffective in starving cancer cells – only that one must follow a strict ketogenic diet without “cheat days” or adding to many carbohydrates to their diet.

So, obviously, glucose metabolism is bad since cancer loves glucose. But, what about fructose (you know, the “sugar” in fruit)?

Another line of cancer research has shown that while some cancer cells get their fuel from glucose, others actually prefer to get their fuel from fructose (the sugar found in fruit as well as other places) [10]. This shows some adaptation in fuel sources for cancer cells but only in the types of sugars they use, not in whether they can use sugar based or fat based by-products to produce their fuel. Here, the ketogenic diet helps again as fruits that are higher in fructose or glucose are discouraged. Thereby starving the cancer cells yet again.

Protein & Cancer Formation

Eating too much protein may also play a role in cancer formation as well as in cancer proliferation. This is for several different reasons but primarily has to do with how proteins are broken down by the body into a usable form. Essentially, proteins are broken into amino acids.

First, excess protein in the body is broken down in several processes. The final process, gluconeogenesis, occurs in the liver where a chemical compound (pyruvate) is turned into glucose which is then sent into the blood stream [11]. Unfortunately, this glucose can fuel cancer cells (see above) & will diminish the effects of ketogenic diet in starving the cancer cells.

Second, quite a bit of research is showing that another of the amino acids, glutamine (which is very common in protein sources), will work together with glucose to actually grow tumor cells [12 -14].

Third, there is this little protein present in the body called mTOR (short for mammalian target of rapamycin) which helps regulate cell growth, proliferation, survival, and protein synthesis (among other things). If we throw in some extra protein, and with it a dash of leucine (another amino acid found in protein) – and we can stimulate mTOR as if we had given it three pots of coffee with 15 espresso chasers. When it’s stimulated, it sort of forgets to do some very important things (like controlling & preventing the cancer growth) [15, 16].

Needless to say, that is definitely not what we want. When it’s functioning normally, in a normal healthy person, mTOR doesn’t actually increase your susceptibility to cancer. And, it may help people with cancer avoid muscle wasting. So, a little bit of a good thing is great – but, give it too much protein and it will go from helpful to destructive faster than you can “keto”.

Intermittent Fasting & Cancer

Intermittent fasting is a common practice within the keto community. There are many benefits that can be attributed to intermittent fasting and one of them is the effects it has on cancer. While fasting, our normal cells simply flip a metabolic switch and go into “survival mode” where everything is slowed down, energy use is minimized, and the cell simply waits for another meal. On the other hand, cancer cells don’t have this switch (this could possibly be because of their broken metabolism).

So, they continue to try to grow & reproduce – consuming resources heavily. Only, the fasting state does not give them the resources they need to grow & reproduce. This, essentially, starves these cancer cells (albeit slowly since intermittent fasting is not a constant fasting state – but, with the “always on” state of a cancer cell, even short, intermittent fasts, will slow & starve it) [17-20].

Calorie Restriction

Caloric restriction, while more difficult than intermittent fasting for some, has shown promising results in preventing and starving cancer for the same reasons as intermittent fasting [21-23]. Basically, the cancer runs itself out of a fuel source because of its constant “on” switch. Once that happens, the cancer begins to starve and die off.

Additionally, restricting your caloric intake will positively impact your baseline blood glucose levels which, in turn, reduces inflammation.

The ketogenic diet certainly makes caloric restriction much more tolerable as the high quality fats tend to leave you feeling fuller longer and keeps your energy metabolism & mood more stable once you are in nutritional ketosis.

Vitamin D

Vitamin D deficiency plays a crucial role in cancer development [24]. So, to decrease your risk of cancer, you must optimize your vitamin D levels with sun exposure. If you are being treated for cancer, you will need even higher levels of Vitamin D. Vitamin D has been found to offer cancer protection in several ways:

  • Regulating genetic expression
  • Increasing the self-destruction of mutated cells
  • Reducing the spread of reproduction of cancer cells
  • Causing cells to become differentiated
  • Reducting the growth of new blood vessels from pre-existing ones

Sleep

Sleep is a three fold factor. First, you must get enough sleep, second, you need to get continuous sleep and third, you need to sleep between certain hours for optimal effectiveness of your sleep time. Studies have shown that disrupted sleep can speed up cancer growth [25].

Additionally, research has confirmed that sleep between the hours of 10pm and 6 am are the optimal hours as certain hormonal fluctuations occur through the day and night & if you are engaging in the right activities during those times, you are able to get the most out of those fluctuation and the activity.

For example, there is a spike in melatonin that occurs between midnight and 1 am that actually decreases the estrogen your body is producing AND boosts your immune system [27-28].

A definite three-for-one deal that just keeps getting better. Other studies have shown that if you go to bed after 10, it could significantly increase your risk of breast cancer. So, make sure to get those zzz’s!

Mechanisms for dealing with stress

Stress causes major issues within our bodies. It depresses the immune system and it also raises the risk of certain cancers. I would love to tell you to avoid stress. However, I know that we all live in the real world where there is stress.

So, find what works for you – a midday walk, a quick puzzle game, a breath of fresh air, yoga, etc. Whatever helps you reduce your stress, go for it.

Exercise

You didn’t think that there was a link between exercise and cancer? Think again. Exercise reduces elevated insulin levels (hey, so does a ketogenic diet – so, imagine the benefits of doing BOTH in decreasing your cancer risk!) and that discouraged the growth & spread of the cancer cells.

Also, exercise helps the circulation of immune cells throughout your body – those little fighters of ours that defend us from everything from a minor cold to life threatening things like cancer.

Exercise with intermittent fasting has been shown to seriously reduce your cancer risk & stimulate healing throughout your body. So, imagine what a ketogenic diet, exercise, and intermittent fasting could do in your healing journey. This isn’t a case of if one pill is good, two is better.

Using a multi-faceted approach to your healing can speed it along as different systems work together, as they were meant to do, to promote a healthy, happy you.

References

  1. Hanahan D, Weinberg, RA: The hallmarks of cancer. Cell 2000, 100:57-70.
  2. Warburg O: The Metabolism of Tumours. New York Richard R Smith 1931.
  3. Warburg O: On the origin of cancer cells. Science 1956, 123:309-314.
  4. Warburg O: The prime cause of cancer and prevention – Part 2. Annual meeting of Nobelists at Lindau, Germany 1969.
  5. Kim JW, Dang CV: Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res 2006, 66:8927-8930.
  6. Hsu PP, Sabatini DM: Cancer cell metabolism: Warburg and beyond. Cell 2008, 134:703-707.
  7. Shaw RJ: Glucose metabolism and cancer. Current opinion in cell biology 2006, 18:598-608.
  8. Jones RG, Thompson CB: Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009, 23:537-548.
  9. Bonucelli G, Tsirigos A: Ketones and lactate “fuel” tumor growth and metastasis. Cell Cycle. Sep 1, 2010; 9(17): 3506-3514.
  10. Liu H, Huang D, et al: Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth. Cancer Res August 1, 2010 70; 6386.
  11. Layman, D: The Role of Leucine in Weight Loss Diets and Glucose Homeostasis. J Nutr. 2003 133: 261S-267S.
  12. Hensley CT, Wasti AT, DeBarardinis RJ: Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest. 2013; 123(9):3678-3684.
  13. Dang, CV: Links between metabolism and cancer. Genes & Dev. 2012. 26:877-890.
  14. Kaadige MR, Looper RE, et al: Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity. PNAS. 106(35) 14878-14883.
  15. Dann SG et al.: mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer, Trends Mol. Med. (2007).
  16. Sheen JH, Zoncu R, Kim D, Sabatini DM: Defective regulation of autophagy upon leucine deprivation reveals a targetable liability of human melanoma cells in vitro and in vivo. Cancer Cell, May 16, 2011.
  17. Safdie FM, et al.: Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). Dec 2009 1(12): 988-1007.
  18. Bezaltis A: Cancer Research Findings Explained. USC News February 2, 2009.
  19. Siegel I, Liu TL, Nepomuceno N, Gleicher N: Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. Cancer Invest. 1988; 6(6):677-80.
  20. Lee C, Raffaghello L, Brandhorst S, et al.: Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012 Mar 7; 4(124): 124ra27.
  21. Mufti, SI: Nutrition and Cancer Prevention. pp 91-97.
  22. Hursting SD, Dunlap SM, Ford NA, Hursting MJ, Lashinger LM: Calorie restriction and cancer prevention: a mechanistic perspective. Cancer & Metabolism 2013, 1:10
  23. Mulcahy N: Calorie Restriction to Treat Cancer: The Time is Now (opinion with resources). Medscape Medical News >Oncology February 1, 2013.
  24. Vitamin D and Cancer Prevention: National Cancer Institute at the National Institutes of health
  25. Paddock, C. (2014, January 28). “Disrupted sleep speeds up cancer.” Medical News Today.
  26. Girschik J, Heyworth J, Fritschi L: Self-reported sleep duration, sleep quality, and breast cancer risk in a population-based case-control study. Am J Epidemiol 2013; 177(4):316-327.
  27. Schernhammer ES, Kroenke CH, Laden F, Hankinson SE: Night Work and the Risk of Breast Cancer. Epidemiology: January 2006 17(1):108-111
  28. Reiter RJ, Tan DX, Korkmaz A, et al.: Light at Night, Chronodisruptions, Melatonin Suppression, and Cancer Risk: A Review. Critical Reviews in Oncogenesis 2007. 13(4).

Further Reading

  1. Seyfried TN, Kiebish MA, et al.: Metabolic management of brain cancer. Bioenergetics of Cancer June 2011. 1807(6): 577-594.
  2. Seyfried TN, Shelton LM: Cancer as a metabolic disease. Nutrition & Metabolism 2010 7:7
  3. Schmidt M, Pfetzer N, et al.: Effects of a Ketogenic Diet on the Quality of Life in 16 Patients with Advanced Cancer. Nutr Metab. 2011; 8(54).

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