Wednesday, July 7, 2010

Cancer Diet Redux: When is the "Cancer Diet" not recommended?

When should the "cancer diet" not be fed to veterinary cancer patients?

We should begin by determining when the "cancer diet" *should* be fed to cancer patients. It is fairly universally recognized now that cancer cells exhibit increased glucose utilization compared to normal cells, and this metabolic defect is the basis for research to determine whether lowering glucose concentrations (by limiting simple carbohydrates in the diet) can improve cancer survival.

Clinical proof that a low carbohydrate diet is clinically beneficial remains a little lean. A single clinical trial in dogs suggested that a low carbohydrate, high fat diet containing fish oil and arginine accelerated time to remission in lymphoma patients and may extend the disease-free interval. Every cancer is different, and test tube studies on human cancer cells suggest that different cancers respond differently to various nutritional profiles in their media.

While a few million dollars has likely been spent on canine research in this area, billions have been spent in human nutritional oncology. And we still don't have definitive proof as to the best diet for cancer patients. In dogs and the cats, the usual recommendation is to feed a low carb diet simply because there is a physiologic rationale for it. In people, it is recommended that they eat the diet that helps prevent cancer - low in animal fat, high in vegetables, full of variety - and people should continue to get exercise. And while there is plenty of evidence in people that excess weight *loss* during cancer treatment worsens the prognosis, there is now emerging evidence that being obese while undergoing cancer treatment also worsens prognosis.

The dietary key to influencing cancer proliferation is that the diet be high in fat - tumor cells are unable to use fat as an energy source, whereas dogs and cats can do this very efficiently. So the "low carb diet" for cancer patients is usually quite high in meat (which contains a lot of fat), low in starches and sugars, and contains added fat. A logical conclusion is that for pets with cancer only - no pancreatitis, no advanced renal disease, no obesity, etc - a low carb, moderate protein, high fat food makes sense. But for patients with these other disorders, the diet can not only worsen the prognosis but even make death from the other disease more imminent than death from cancer.

I'd like to focus here on managing obesity in a cancer patient. Here's the thing - obesity leads to hyperglycemia - high blood glucose - and insulin resistance. This hyperglycemia is much more persistent than the elevated glucose load that occurs after any meal of any composition. In addition, surgery, radiation and chemotherapy can cause changes in endocrine functions that could increase the likelihood of development of metabolic syndrome (de Haas, 2010).Cancer itself is commonly associated with hyperglycemia (Heber, 2006). Whether this persistent hyperglycemia and insulin resistance leads to worse outcomes in veterinary patients is unknown, but glycemic control is routinely recommended in human patients when hyperglycemia is identified (Heber, 2006). This is both to control episodes of infection (made more likely through the use of immunesuppressive therapies) but also to prevent progression to metabolic syndrome and diabetes which is a risk factor for the development of other cancers.

Obesity is also an 'inflammatory disease', as is cancer. Fat is now considered an organ that releases excess infl ammatory cytokines, such as tumor-necrosis-factor-α (TNFα) and interleukin 6 (IL-6) (de Haas, 2010). These cytokines are considered growth factors that can activate genes that control angiogenesis, invasion and metastasis of cancer cells.

The obese cancer patient then gets a double dose of simple sugar in the blood, and more inflammatory chemicals already being produced by the tumor itself. These patients just have to be 'sicker' - whether or not they show it - than patients of normal weight. Hence the new evidence that some obese human cancer patients have worse outcomes than people of normal weight. This has been shown most frequently in breast, prostate and colon cancer (Ramos 2010, Sinicrope 2010, Komaru 2010, Siegel 2010, de Azambuja 2010, Lange 2008, Nitori 2009). Additionally, some recent trials suggest that overweight patients undergoing controlled weight loss during cancer treatment experienced improved prognosis (Freedland 2009).

A diet that is low in simple carbohydrates and higher in meat protein will be fairly calorie-dense, depending on the proportion of meat to other ingredients. A homemade version of the low carb diet can be made to resemble an Atkins-style diet. This can work for weight loss in some patients but not necessarily for others, because meat comes with fat - even the lower fat meats. If I formulate a diet for an obese patient, I use a lower fat protein, such as tofu, often along with a small amount of a starch, and plenty of vegetables. These proportions are customized to the individual dog, and the vitamin/mineral levels are also changed as needed. The starch and sugar content is still quite low, and weight loss can be facilitated.

I see many people who request the 'cancer diet' for their pet with cancer, and a few who refuse to believe that it is inappropriate for their particular pet. We have an increasing number of studies in people to suggest that customizing the diet for an obese patient improves survival, and only 1 study in dogs suggesting that the high fat low carb diet makes a difference in survival. The veterinary oncologist that investigated the low carbohydrate diet for veterinary cancer patients has repeatedly written "no one diet is right for every cancer patient". You can't believe that his research is right 100% of the time but that this opinion of his is wrong 100% of the time.


References

de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JP, Vicente M, Giuliani R, Nordenskjöld B, Gutiérez J, Andersson M, Vila MM, Jakesz R, Demol J, Dewar J, Santoro A, Lluch A, Olsen S, Gelber RD, Di Leo A, Piccart-Gebhart M.The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial. Breast Cancer Res Treat. 2010 Jan;119(1):145-53.

de Haas EC, Oosting SF, Lefrandt JD, Wolffenbuttel BH, Sleijfer DT, Gietema JA. The metabolic syndrome in cancer survivors. Lancet Oncol. 2010 Feb;11(2):193-203.

Freedland SJ, Aronson WJ. Dietary intervention strategies to modulate prostate cancer risk and prognosis. Curr Opin Urol. 2009 May;19(3):263-7.

Heber, D. Assessing Endocrine Effects of Cancer and Ectopic Hormone Syndromes. Nutritional oncology. Elsevier, St Louis, 2006; p. 695

Komaru A, Kamiya N, Suzuki H, Endo T, Takano M, Yano M, Kawamura K, Imamoto T, Ichikawa T. Implications of body mass index in Japanese patients with prostate cancer who had undergone radical prostatectomy. Jpn J Clin Oncol. 2010 Apr;40(4):353-9. Epub 2010 Jan 10.

Lange BJ, Smith FO, Feusner J, Barnard DR, Dinndorf P, Feig S, Heerema NA, Arndt C, Arceci RJ, Seibel N, Weiman M, Dusenbery K, Shannon K, Luna-Fineman S, Gerbing RB, Alonzo TA. Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group. Blood. 2008 Feb 1;111(3):1044-53. Epub 2007 Nov 13.

Nitori N, Hasegawa H, Ishii Y, Endo T, Kitagawa Y. Impact of visceral obesity on short-term outcome after laparoscopic surgery for colorectal cancer: a single Japanese center study. Surg Laparosc Endosc Percutan Tech. 2009 Aug;19(4):324-7.

Ramos Chaves M, Boléo-Tomé C, Monteiro-Grillo I, Camilo M, Ravasco P. The diversity of nutritional status in cancer: new insights. The Oncologist 2010; 15(5):523 -530

Siegel EM, Ulrich CM, Poole EM, Holmes RS, Jacobsen PB, Shibata D. The effects of obesity and obesity-related conditions on colorectacl cancer prognosis. Cancer Control 2010; 17(1):52-57.

Sinicrope FA, Foster NR, Sargent DJ, O'Connell MJ, Rankin C. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010 Mar 15;16(6):1884-93. Epub 2010 Mar 9.

1 comment:

  1. Very interesting. I've read that the incience of cachexia seems to be lower in dogs than in humans (Evaluation of body condition and weight loss in dogs presented to a veterinary oncology serviceJ Vet Intern Med. 2004 Sep-Oct;18(5):692-5. Kathryn E Michel1, Karin Sorenmo, Frances S Shofer), but I hadn't considered the issue of obesity as a potential negative prognostic factor.

    It's frustrating when the best we can do is make recommendations based on first principles, in vitro research, and non-target species clinical research, since unfortunately such recommendations tend to be wrong as often as right. And there is some reason to think the concept of "metabolic syndrome" has been stretched beyond its usefulness (http://www.sciencebasedmedicine.org/?p=5309). Ultimately, it would be best to have better and deeper clinical research on the subject, but this certainly seems like a reasonable recommendation based on what's known now. And I appreciate the emphasis on the fact that universal recommendations for "cancer," as if it were one disease the same in all patients, make no sense.

    My own experience, for what it's worth, is that few cancer patients undergoing treatment seem to achieve or maintain an optimal body condition. Many seem to lose weight if their disease is not amenable to a remission from therapy. And for those who do have a good remission, they seem to gain weight because owners or giving them extra food-as-love! It's difficult to discourage clients from doing this when they're dealing with the impact of the diagnosis, but it looks like I'll have to work harder at it.

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