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Open AccessJournal ArticleDOI

Reduction of weight loss and tumour size in a cachexia model by a high fat diet.

TLDR
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.
Abstract
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.

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Citations
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Journal ArticleDOI

Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

TL;DR: The meaning of physiological ketosis is revisited and whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand are questioned.
Journal ArticleDOI

Fasting and cancer: molecular mechanisms and clinical application

TL;DR: It is proposed that the combination of FMDs with chemotherapy, immunotherapy or other treatments represents a potentially promising strategy to increase treatment efficacy, prevent resistance acquisition and reduce side effects.
Journal ArticleDOI

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

TL;DR: The results indicate that KetoCal® has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors when administered in restricted amounts and should be considered as an alternative therapeutic option for malignant brain cancer.
Journal Article

Anticachectic and Antitumor Effect of Eicosapentaenoic Acid and Its Effect on Protein Turnover

TL;DR: Results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.
Journal ArticleDOI

Ketogenic diet in the treatment of cancer - Where do we stand?

TL;DR: The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy.
References
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Journal ArticleDOI

Brain Metabolism during Fasting

TL;DR: Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that beta-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism.
Book ChapterDOI

D-(–)-3-Hydroxybutyrate

TL;DR: The chapter reviews the entire procedure of this enzymatic method, including the principle, reagents, and solutions used in it, which has its own accuracy, precision, and specificity.
Journal ArticleDOI

Effect of ketone infusions on amino acid and nitrogen metabolism in man.

TL;DR: It is concluded that increased blood ketone acid levels induced by infusions of Na DL-beta-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation.
Journal ArticleDOI

The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation

TL;DR: The findings indicate that the ketotic state induced by the EKD was well tolerated in lean subjects; nitrogen balance was regained after brief adaptation, serum lipids were not pathologically elevated, and blood glucose oxidation at rest was measurably reduced while the subjects remained euglycemic.
Journal ArticleDOI

Host‐tumor interaction and nutrient supply

TL;DR: An apparent differential utilization of fat calories by normal and malignant cells may permit manipulation of the relative benefit of parenteral nutrition to host or to tumor, permitting host repletion without tumor stimulation or alternatively tumor stimulation at appropriate times to increase sensitivity to phase‐specific antineoplastic therapy.
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