Wednesday, September 19, 2007

Ketogenic diet and cancer....(old news)

This is not directly fitness or conditioning related but it is about a low carb diet....so ok, I'll jump on the bandwagon. It seems like just about every blog (even Rif) I read has picked up on this story from Time magazine.

The article is worth a read, but it is not really new stuff. The idea is that you can fight cancer through starving them of sugar. Cancer cells need sugar to survive and grow:

unlike healthy cells, which generate energy by metabolizing sugar in their mitochondria, cancer cells appeared to fuel themselves exclusively through glycolysis, a less-efficient means of creating energy through the fermentation of sugar in the cytoplasm.


The theory is simple: If most aggressive cancers rely on the fermentation of sugar for growing and dividing, then take away the sugar and they should stop spreading. Meanwhile, normal body and brain cells should be able to handle the sugar starvation; they can switch to generating energy from fatty molecules called ketone bodies — the body's main source of energy on a fat-rich diet — an ability that some or most fast-growing and invasive cancers seem to lack.


This all makes sense. But as I said this is not new - it has just been picked up now by a popular news magazine.

There have been people looking at this approach to cancer treatment for a while. For example here is an abstract of an article from earlier this year looking at the same method:

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


Background

Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG).

Methods

Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet.

Results

KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the tumors than in the contralateral normal brain suggesting that these brain tumors have reduced ability to metabolize ketone bodies for energy.

Conclusion


The results indicate that KetoCal® has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors when administered in restricted amounts. The therapeutic effect of KetoCal® for brain cancer management was due largely to the reduction of total caloric content, which reduces circulating glucose required for rapid tumor growth. A dependency on glucose for energy together with defects in ketone body metabolism largely account for why the brain tumors grow minimally on either a ketogenic-restricted diet or on a standard-restricted diet. Genes for ketone body metabolism should be useful for screening brain tumors that could be targeted with calorically restricted high fat/low carbohydrate ketogenic diets. This preclinical study indicates that restricted KetoCal® is a safe and effective diet therapy and should be considered as an alternative therapeutic option for malignant brain cancer.


Emma also had a post on this earlier in the year which is very well written, and points to another article:

Targeting energy metabolism in brain cancer: review and hypothesis

Abstract

Malignant brain tumors are a significant health problem in children and adults and are often unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration, malignant brain cancer is potentially manageable through changes in metabolic environment. A radically different approach to brain cancer management is proposed that combines metabolic control analysis with the evolutionarily conserved capacity of normal cells to survive extreme shifts in physiological environment. In contrast to malignant brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The bioenergetic transition from glucose to ketone bodies metabolically targets brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of tumor cells and is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with dietary energy restriction and the ketogenic diet.


The most sobering thing I read today about all this was in the Male Pattern Fitness blog.
The idea is that tumors thrive on sugars, so if you cut off the supply of sugar with a high-fat, very-low-carbohydrate diet, the tumors stop growing. They might even shrink. It reminded me of a really sad story from a few years back: An acquaintance was diagnosed with cancer, but rather than going through chemotherapy, decided to "heal" his body with a macrobiotic diet, all fruits and vegetables with little protein or fat. The cancer took him in what was probably record time. If this theory is correct, he was right about diet being a weapon against his cancer. But he was dead wrong about the diet he chose.


Another reason to watch the carbs!

1 comment:

Chris said...

Rob Wolff has put up a very interesting post on this topic at

http://robbwolf.com/?p=18