Clinical Evidence on Cancer Cachexia and High Fat Diets

Clinical studies investigating the anti-cachectic effects of high-fat diets for the benefit of cancer patients have been rare, but not nonexistent.
In one of the most recent studies, Shukla et al showed that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss. (Cf Exhibit A). In another study  (one of the first published experimentations, in 1988),  a 70% MCT diet supplemented with b-hydroxybutyrate was given parenterally to five late-stage cachectic patients. After seven days on the diet, mean body weight had increased by 2 kg and their physical performance status had improved. (1)
Still in this perspective, Nebeling et al. investigated the effects of a MCT-based ketogenic diet taken ad libitum (60% MCT oil, 20% protein, 10% CHO, 10% other fats) on body weight and glucose metabolism in two pediatric patients with advanced-stage astrocytoma. Within 7 days on the diet, blood glucose levels had decreased to normal, while glucose uptake by the tumor estimated from FDG-PET scans had decreased by an average value of 21.8%. Notably, body weight remained stable throughout the study period of 8 weeks. (2).
In a randomized controlled study, Breitkreuz et al. showed that by supplementing the normal diet of 11 under-nourished, (3) non-diabetic patients suffering from metastatic gastro-intestinal cancers with a fat-enriched liquid supplementation for 8 weeks, it was possible to reverse the loss of body weight and lean tissue mass and to improve several quality-of-life parameters in the treatment group, while the control group continued to lose body and lean tissue weight (4).
In addition to the improving of the cachetic state, KD has been shown to also reduce the malignancy.  Among other studies, , Tisdale et al. noted that the KD not only attenuated the cachectic effects of the tumor, but also that the tumors grew more slowly (although they did not attribute this to a direct anti-tumor effect of b-hydroxybuty- rate). (EXHIBIT F).
CONCLUSION: ACRI RECOMMENDS MILD KETOSIS FOR CACHETIC CANCER PATIENTS
These above mentioned studies show that a ketogenic diet can be of benefit to cachectic cancer patients.  With the years,  more evidence has emerged from  animal, laboratory and human studies indicating that cancer patients can benefit from a low carb, high fat ketogenic diet. In this realm the great news is that not only is the patient regaining weight, but tumor growth and progression have been shown to stop, if not regress. However, we still don’t understand all of the underlying molecular mechanisms at play. Dozens of clinical trials involving some form of KD for cancer are still pending.
PRECISION AND FOOTNOTES
(1). Fearon KC, Borland W, Preston T, Tisdale MJ, Shenkin A, Calman KC: Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism. Am J Clin Nutr 1988, 47:42-48.
(2).  Nebeling LC1, Lerner E. Implementing a ketogenic diet based on medium-chain triglyceride oil in pediatric patients with cancer. J Am Diet Assoc. 1995 Jun;95(6):693-7.
(3). The supplement contained 66% energy from fat, of which 45% were monounsaturated, 27% saturated (both LCT and MCT) and 28% polyunsaturated; mean energy intake ranged between 1000 and 2000 kcal/day and tended to be higher in patients receiving the additional fat drink.
(4). Breitkreutz R, Tesdal K, Jentschura D, Haas O, Leweling H, Holm E: Effects of a high-fat diet on body composition in cancer patients receiving chemotherapy: a randomized controlled study. Wien Klin Wochenschr 2005, 117:685-692.
EXHIBIT A
Cancer Metab. 2014 Sep 1;2:18. doi: 10.1186/2049-3002-2-18. eCollection 2014.
Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia.
Shukla SK1, Gebregiworgis T2, Purohit V3, Chaika NV1, Gunda V1, Radhakrishnan P1, Mehla K1, Pipinos II4, Powers R2, Yu F5, Singh PK6.
Cancer Metab. 2014;2:22.
BACKGROUND:
Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy.
RESULTS:
We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia.
CONCLUSIONS:
Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss.
EXHIBIT B
Am J Clin Nutr. 1988 Jan;47(1):42-8.
Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism.
Fearon KC1, Borland W, Preston T, Tisdale MJ, Shenkin A, Calman KC.
Author information
Abstract
The aim of this study was to determine whether a ketogenic diet could decrease nitrogen losses in cachectic cancer patients and at the same time reduce the supply of glucose for tumor energy metabolism. Five patients with malignant disease and severe weight loss (mean 32%) were fed via a fine bore nasogastric tube. A normal diet was given for 6 d and this was followed by 7 d of an isonitrogenous, isocaloric, ketogenic diet. Both diets were well tolerated. At 7 d the mean ketone body concentration in the blood of patients fed the ketogenic diet was 1.21 +/- 0.33 mM. This ketosis was associated with a significant reduction of the concentration in blood of glucose, lactate, and pyruvate (p less than 0.05). There was, however, no significant alteration in host N balance or whole-body protein synthesis, degradation, or turnover rates. Whether the change from glucose- to fat-derived energy substrates might reduce tumor growth rates in the long term remains to be determined.
EXHIBIT C
Am J Clin Nutr. 1988 Jan;47(1):42-8.
Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism.
Fearon KC1, Borland W, Preston T, Tisdale MJ, Shenkin A, Calman KC.
The aim of this study was to determine whether a ketogenic diet could decrease nitrogen losses in cachectic cancer patients and at the same time reduce the supply of glucose for tumor energy metabolism. Five patients with malignant disease and severe weight loss (mean 32%) were fed via a fine bore nasogastric tube. A normal diet was given for 6 d and this was followed by 7 d of an isonitrogenous, isocaloric, ketogenic diet. Both diets were well tolerated. At 7 d the mean ketone body concentration in the blood of patients fed the ketogenic diet was 1.21 +/- 0.33 mM. This ketosis was associated with a significant reduction of the concentration in blood of glucose, lactate, and pyruvate (p less than 0.05). There was, however, no significant alteration in host N balance or whole-body protein synthesis, degradation, or turnover rates. Whether the change from glucose- to fat-derived energy substrates might reduce tumor growth rates in the long term remains to be determined.
 EXHIBIT D
Br J Cancer. 1987 Jul;56(1):39-43.
Reduction of weight loss and tumour size in a cachexia model by a high fat diet.
Tisdale MJ, Brennan RA, Fearon KC.
An attempt has been made to reverse cachexia and to selectively deprive the tumour of metabolic substrates for energy production by feeding a ketogenic regime, since ketone bodies are considered important in maintaining homeostasis during starvation. As a model we have used a transplantable mouse adenocarcinoma of the colon (MAC 16) which produces extensive weight loss without a reduction in food intake. When mice bearing the MAC16 tumour were fed on diets in which up to 80% of the energy was supplied as medium chain triglycerides (MCT) with or without arginine 3-hydroxybutyrate host weight loss was reduced in proportion to the fat content of the diet, and there was also a reduction in the percentage contribution of the tumour to the final body weight. The increase in carcass weight in tumour-bearing mice fed high levels of MCT was attributable to an increase in both the fat and the non-fat carcass mass. Blood levels of free fatty acids (FFA) were significantly reduced by MCT addition. The levels of both acetoacetate and 3-hydroxybutyrate were elevated in mice fed the high fat diets, and tumour-bearing mice fed the normal diet did not show increased plasma levels of ketone bodies over the non-tumour-bearing group despite the loss of carcass lipids. Both blood glucose and plasma insulin levels were reduced in mice bearing the MAC16 tumour and this was not significantly altered by feeding the high fat diets. The elevation in ketone bodies may account for the retention of both the fat and the non-fat carcass mass. This is the first example of an attempt to reverse cachexia by a diet based on metabolic differences between tumour and host tissues, which aims to selectively feed the host at the expense of the tumour.
EXHIBIT E
J Am Diet Assoc. 1995 Jun;95(6):693-7.
Implementing a ketogenic diet based on medium-chain triglyceride oil in pediatric patients with cancer
.
Nebeling LC1, Lerner E.
Traditionally, a ketogenic diet is given to drug-resistant children with epilepsy to improve seizure control. Inducing a ketogenic state in patients with cancer may be a useful adjunct to cancer treatment by affecting tumor glucose metabolism and growth while maintaining the patient’s nutritional status. A ketogenic diet consisting of 60% medium-chain triglyceride (MCT) oil, 20% protein, 10% carbohydrate, and 10% other dietary fats was provided to a select group of pediatric patients with advanced-stage cancer to test the effects of dietary-induced ketosis on tumor glucose metabolism. Issues of tolerance and compliance for patients consuming an oral diet (consisting of normal table foods and daily MCT oil “shakes”) and for patients receiving an enteral formula are reviewed. Preliminary use of the MCT oil-based diet suggests a potential in pediatric patients with cancer.
EXHIBIT F
Br J Cancer. 1988 Nov;58(5):580-3.
A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model.
Tisdale MJ1, Brennan RA.
A comparison has been made between the ability of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size.
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DISCLAIMER: Nothing in this educational post is to be construed as medical advise.

Professor Joubert teaches how to extend a healthy cancer-free Lifespan to 122 years thanks to safe, efficient and cost friendly breakthrough protocols. Working on a documentary and book that redefines Medicine in light of new discoveries, ancient wisdoms, innovative research and holistic science, he can be nonetheless available to coach patients back to homeostasis, wellbeing & Joie de Vivre. On occasion, Pr. Joubert can also coach health professionals to better protect their holistic practice when they must deviate from outdated and-or irrational mainstream “standards of care” in order to genuinely serve their patients, evidence-strong Science and internationally recognized human rights. For details, see the links called “Contact” and “Mission” (under the “About” link).

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