Carbs and cancer

This is not one of those “carbs cause cancer” posts. I though “Carbs and cancer” had a better ring to it than for example “Metabolism and cancer”, what with the alliteration and all. Still, it’s important to remember that although carbohydrate restriction is an effective treatment for cancer, this does not mean cancer is caused by consumption of carbs.

Our diet determines our health, even our risk of getting cancer and our risk of surviving it. Her are some reasons macronutrients matter:

The cause

– Humans who live on natural diets seem free of many cancers and also free of metabolic diseases [1]. Metabolic diseases such as obesity, diabetes, insulin resistance and heart disease, also coexist with cancer.

– A high body mass index increases the risk of most cancers [2].

– Cancer cells are normal cells that grow too fast and the cells need both energy and growth factors to grow at an increased pace. A logical theory of treatment would be to take away the energy and growth factors and starve the cancer cells.

– Hanahan and Weinberg suggested that six essential alterations in cell physiology could underlie malignant cell growth [3]. These six alterations were described as the hallmarks of nearly all cancers and included, 1) self-sufficiency in growth signals, 2) insensitivity to growth inhibitory signals, 3) evasion of programmed cell death (apoptosis), 4) limitless replicative potential, 5) sustained vascularity (angiogenesis), and 6) tissue invasion and metastasis.

Cancer cells crave glucose. Aerobic glycolysis, the breaking down of glucose in the presence of oxygen, but with high lactic acid production in the cytoplasm (the Warburg effect), is a metabolic hallmark of most tumors [3]. Almost all cancers express aerobic glycolysis, regardless of their tissue or cellular origin.

Enhanced glycolysis (the breakdown of glucose) is required for the rapid growth and survival of many tumor cells.

– People with type 2 diabetes are at increased risk of getting pancreatic, liver, colorectal, and bladder cancers, and non-Hodgkin lymphoma [4]. But if you have type 1 diabetes you have a reduced risk of lung cancer, Hodgkin’s lymphoma and prostate cancer.

Mitochondrial dysfunction is a key element in most cancers.

– One of the problems if you are insulin resistant is that the mitochondria are bombarded with energy and pushed to the max. This causes them to produce reactive oxygen species (ROS). Increased ROS production can impair genome stability, tumor suppressor gene function and control over cell proliferation [3].

– The glycolytic enzyme «glyceraldehyde-3-phosphate dehydrogenase» potential is upregulated in many common tumors. GAPDH is also a transcription activator and link the metabolic state to gene transcription.

– The integrity of the nuclear genome is largely dependent on the functionality and energy production of the mitochondria.

– Impaired mitochondrial function can also induce abnormalities in tumor suppressor genes and oncogenes.

– Some viruses are associated with certain cancers. Several of these viruses are known to affect the mitochondria.

– While the mutator phenotype of cancer can be linked to impaired mitochondrial function, normal mitochondrial function can suppress tumorigenesis. We can suppress cells capability of causing tumors by fusing cytoplasm from normal cells without a nucleus with tumor cells. This suggests that normal mitochondria can suppress the tumorigenic phenotype [3].

– The function of a tumor suppressor gene called p53 is linked to cellular respiration. Damage to the respiration will gradually reduce p53 function.

– The study of cancer and metabolism involves such fancy words as «the Warburg effect» and «von Hippel-Lindau,» so there’s got to be something to it 🙂

If cancer is a disease of energy metabolism, then a rational approach to cancer management can be found in therapies that target energy metabolism. 
The cure

– Growth and progression of cancers of the mammary, brain, colon, pancreas, lung, and prostate has been reduced following energy restriction.

– Due to accumulated genetic mutations, cancer cells lack metabolic flexibility, so shifting the metabolism makes sense.

– Many tumors have abnormalities in the genes and enzymes needed to metabolize ketone bodies for energy so ketogenic diets are especially potent.

– It is well established that dietary energy restriction protects against cancer in many animal models, but…

– Freedland and coworkers transplanted prostate cancer cells into mice. The mice were then divided into one ketogenic group, one low fat group and one western diet. After 51 days the tumor volume in the low carb mice was 33% smaller than the other two groups, despite similar energy intake [5].

– Zhou and coworkers put mice with malignant brain cancer on a ketogenic diet meant for epilepsy and showed that the diet decreased the intracerebral growth by 65% compared to mice on control diet [6].

– LJ Martin and coworkers randomized women to a low fat diet or a control group, hoping to affect the risk of breast cancer. They did. But not how they wanted. Over an average of 10 years low fat eating led to 118 invasive breast cancers while the control had 102. Carbohydrate intake was found to correlate with cancer risk [7].

– A group of Japanese researchers [8] hypothesized that the increase in colorectal cancer in Japan could be due to increased fat intake. So they told 373 people with previous cancer to restrict their fat energy ratio to 18-22%. After 4 years the researchers were surprised to find that fat restriction had increased the risk of cancer recurrence.

– A group of Italian researchers found direct relations between dietary GI and GL and risk of renal cell carcinoma [9].

– In 1995, two pediatric patients with malignant Astrocytoma tumors were put on a 60% MCT diet to induce ketosis. PET scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects One patient exhibited significant clinical improvements in mood and new skill development during the study- continued the diet and remained free of cancer progression [10].

– An Italian case control study from 1996 found that the risk of breast cancer decreased with increasing total fat intake and that the risk increased with increasing intake of available carbohydrates [11].

Eugene Fine at Albert Einstein College of Medicine of Yeshiva University, have been using a 1 month Atkins diet in cancer patients, hoping to see a reduction in tumor size. Results have not been published yet.

Stephen J. Freedland at Duke Univeristy is currently testing the hypothesis that an Atkins diet will prevent or at least minimize the metabolic consequences of androgen deprivation therapy in prostate cancer treatment.

The University of Würzburg Hospital has recommended a low carb, ketogenic diet for cancer patients since 2007

– Other studies are testing ketogenic diets in relation to cancer treatment. There’s much interesting knowledge to come

 

Impaired mitochondrial energy metabolism seems to underlie the origin of most cancers. To improve mitochondrial function: avoid toxic foods, read the Perfect Health Diet, avoid foods that induce inflammation, make sure to produce ketones now and then and remember to exercise. 

References

1. Lindeberg S: Food and western disease: health and nutrition from an evolutionary perspective. Chichester: Wiley-Blackwell; 2010.

2. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008, 371: 569-578.

3. Seyfried TN, Shelton LM: Cancer as a metabolic disease. Nutr Metab (Lond) 2010, 7: 7.

4. Tabares-Seisdedos R, Dumont N, Baudot A, Valderas JM, Climent J, Valencia A, Crespo-Facorro B, Vieta E, Gomez-Beneyto M, Martinez S, Rubenstein JL: No paradox, no progress: inverse cancer comorbidity in people with other complex diseases. Lancet Oncol 2011, 12: 604-608.

5. Freedland SJ, Mavropoulos J, Wang A, Darshan M, Demark-Wahnefried W, Aronson WJ, Cohen P, Hwang D, Peterson B, Fields T, Pizzo SV, Isaacs WB: Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. Prostate 2008, 68: 11-19.

6. Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN: The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond) 2007, 4: 5.

7. Martin LJ, Li Q, Melnichouk O, Greenberg C, Minkin S, Hislop G, Boyd NF: A randomized trial of dietary intervention for breast cancer prevention. Cancer Res 2011, 71: 123-133.

8. Nakamura T, Ishikawa H, Takeyama I, Kawano A, Ishiguro S, Otani T, Okuda T, Murakami Y, Sakai T, Matsuura N: Excessive fat restriction might promote the recurrence of colorectal tumors. Nutr Cancer 2010, 62: 154-163.

9. Galeone C, Pelucchi C, Maso LD, Negri E, Talamini R, Montella M, Ramazzotti V, Bellocco R, Franceschi S, La Vecchia C: Glycemic index, glycemic load and renal cell carcinoma risk. Ann Oncol 2009, 20: 1881-1885.

10. Nebeling LC, Miraldi F, Shurin SB, Lerner E: Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 1995, 14: 202-208.

11. Franceschi S, Favero A, Decarli A, Negri E, La Vecchia C, Ferraroni M, Russo A, Salvini S, Amadori D, Conti E, Montella M, Giacosa A: Intake of macronutrients and risk of breast cancer. Lancet 1996, 347: 1351-1356.

http://www.time.com/time/health/article/0,8599,1662484,00.html

12 kommentarer om “Carbs and cancer”

  1. Very nice post, Pal, and thanks for the link. One addendum for any cancer patients reading this: Although carb calories are problematic in cancer, many plants contain bioactive compounds that have anti-cancer effects. So while you want a low-carb diet with intermittent fasting and MCT or coconut oil consumption for ketosis, you don't want a low-plant-food diet. Vegetables are good for you.

    Liker

  2. I believe that in the Freeland study polyunsaturated fat wasn't that low, giving even more support for the ketogenic diet, considering the known cancer promoting effects of PUFA. But, for the low fat diet, the carbs were sucrose, so I'd like to see what it would be with a starch source.

    Liker

  3. Like the references to mitochondria. There is an MD on the web (Mike Nichols – whenyouareserious.com) that is a big proponent of improving mitochondrial function to improve health. He has some very good material on his site.

    Liker

  4. majkinetor, you're right. Cancer cells are not actually starved. High blood glucose just provides more energy for cancer cells then low blood glucose.

    gfm, I cannot find any such studies. I don't know enough about CLL, but as far as I can see the advise from Paul Jaminet is good advice. Whether chronic ketosis is better then intermittent ketosis, i don't know.

    Liker

  5. Hi Pål,

    Sorry to go off topic here, but I'm interested in your thoughts on the recent studies done by Berit Johansen from NTNU. I'm Dutch, but I understand Norwegian. I just watched this lecture:

    http://www.ustream.tv/recorded/10912371#utm_campaign=synclickback&source=deniedbyhost&medium=10912371

    A 65 % carb diet increases expression of genes involved in inflammation, while an isocaloric diet with equal energy percentages from carbs, fat and protein lowers expression of these genes. Based on this finding, Johansen gives the recommandation to ignore the official dietary guidelines and to follow a paleo approach in stead. I buy that, of course, but then she goes on to say that it is also very important to eat regularly: three meals and two snacks per day.

    Do you know on what evidence she bases this 'grazing' advise? As far as I can see she didn't play with meal frequency in het experiments. It runs counter to what I think to know at this moment.

    Thanks for your view.

    Liker

  6. Hi Melchior

    This is really interesting, but I haven’t gotten hold of the original studies. The findings are interesting, but it seems to me that the researchers are over interpreting the data.

    The researchers measured gene expression, but gene expression is very different from actual health parameters. Most other studies show more favorable results from low carb compared to medium carb, so it’s hard to imagine this study showing something new and different.

    Also, the diet study they did was a meal replacement study. No real food. The highest carb diet caused a larger expression of genes related to inflammation and CVD. The type of fat also differed between diets. I would follow a paleo diet, but not based on these findings. I’ve heard nothing about meal frequency from their study. You should email her about it.

    These researchers aren’t very informed and that might be why they are so excited about previously well documented findings such as reduced serum triglycerides after increased fat intake.

    Liker

  7. Thanks for your prompt reply, Pål. I also wonder what conclusions we can draw from changes in gene expression. In the press release she says ‘we should not fall into the low carb trap either’, but as far as I can see she did not measure the effect of a low carb intervention. So on what evidence does she base this? I will mail her and keep you posted. Her apparent exitement about falling triglicerides with lower carb intake was puzzeling indeed! I almost can’t believe her surprise was real. The funny thing is that Berit Johansen was the scientist who made me aware of the potential of ‘paleo’ back in 1999! I then read this article in Gemini:

    http://www.ntnu.no/gemini/1999-02/4.html

    Since that day she has been kind of a heroe to me. Maybe she been staring at these micro arrays a bit too much. I don’t blame her, but it’s a shame. People like her could be enormous allies.

    Liker

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