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Cancer as a metabolic disease

http://www.nutritionandmetabolism.com/content/7/1/7

Cancer as a metabolic disease

Thomas N Seyfried email and Laura M Shelton email

Nutrition & Metabolism 2010, 7:7doi:10.1186/1743-7075-7-7
Published: 27 January 2010
Abstract (provisional)

Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

The complete article is available as a provisional PDF.

Quote:

Conclusions
Evidence is reviewed supporting a general hypothesis that cancer is primarily a disease of energy metabolism. All of the major hallmarks of the disease can be linked to impaired mitochondrial function. In order to maintain viability, tumor cells gradually transition to substrate level phosphorylation using glucose and glutamine as energy substrates. While cancer causing germline mutations are rare, the abundance of somatic genomic abnormalities found in the majority of cancers can arise as a secondary consequence of 31 mitochondrial dysfunction. Once established, somatic genomic instability can contribute to further mitochondrial defects and to the metabolic inflexibility of the tumor cells. Systemic metastasis is the predicted outcome following protracted mitochondrial damage to cells of myeloid origin. Tumor cells of myeloid origin would naturally embody the capacity to exit and enter tissues. Two major conclusions emerge from the hypothesis; first that many cancers can regress if energy intake is restricted and, second, that many cancers can be prevented if energy intake is restricted. Consequently, energy restricted diets combined with drugs targeting glucose and glutamine can provide a rational strategy for the longerterm management and prevention of most cancers.

Patrick

Thanks for posting this link and abstract. It's fascinating. I'm very interested in the effect of intermittent fasting and carb restriction on cancer prevention and treatment, and this article (admittedly challenging for me to understand) suggests that research is pursuing answers to those questions. Many thanks!

I think this is an excellent well thought out paper. The full text is online free if you click the provisional PDF link in the box. Although some parts are a bit complex if you stick with it there is plenty there you will find easier. I think we are all aware of the following.

Quote:

A transition from carbohydrate to ketones for energy is a simple way to target energy metabolism in glycolysis-dependent tumor cells while enhancing the metabolic efficiency of normal cells. The shift from the metabolism of glucose to the metabolism of ketone bodies for energy is due largely to the shift in circulating levels of insulin and glucagon, key hormones that mediate energy metabolism. Insulin, which stimulates glycolysis, is reduced under dietary restriction, while glucagon, which inhibits glycolysis and mobilizes fats, is increased.
Glucose reduction not only reduces insulin, but also reduces circulating levels of IGF-1, which is necessary for driving tumor cell metabolism and growth

it boils down to many cancer cells need sugar to reproduce. Ill bet that study won't make a big splash in the mainstream media.

And I bet that at least one of the 31 possible mitochondrial dysfunctions is a result of glycation, or more specifically advanced glycation end-product, just another effect of sugar.

Cancer proliferation and therapy: the Warburg effect and quantum metabolism
those who found the original paper interesting may also enjoy this one.

From the paper mentioned in my previous post I found this
Energy-modulating vitamins – a new combinatorial therapy prevents cancer
cachexia in rat mammary carcinoma
In conclusion, the above ﬁndings indicate that net ATP production was diminished in tumour-bearing animals, which ultimately leads to cancer cachexia.
Treatment with EMV enhanced the activities of the Krebs cycle enzymes, and oxidative phosphorylation as a consequence enhanced ATP production.
This increased amount of ATP was utilized by normal cells for their routine metabolism, reducing the cancer cachexia.
In addition, the anti-carcinogenic and anti-proliferative effects of EMV suppress tumour cell proliferation.
This suggests that the new combination of EMV could be of major therapeutic value in breast cancer management.

They were looking at some ways improving Mitochondrial function may improve cancer prognosis.
The energy-modulating vitamins used were riboﬂavin (45mg/kg body weight per d), niacin (100mg/kg body weight per d) and coenzyme Q10 (40mg/kg body weight per d) for 28 d. It's a rat study and scaling those amounts up to human terms results in quite high doses.

But it makes me wonder if the answer to Eades/Colpo argument over metabolic advantage may be found in the many roles of mitochondria?

Long article -- The Concept of Gamma-Glucose

Quote:

he opined that there was a qualitative difference between dietary glucose from sugar and starch and the kind received from animal fats.

So far as I can tell, the gist is that the body turns fat into a kind of glucose that it can burn easily, while glucose in the diet can't be burned as well. However, if anyone reads this & understands it better, dish. :)

I keep coming across studies like this one. Thanks for posting this :thup:

Thanks for posting this.

I don't believe there is a Gamma-Glucose

http://www.rpi.edu/dept/bcbp/molbio...Monosaccharides

Quote:

Originally Posted by LC FP

I don't believe there is a Gamma-Glucose

Me either. After going to the link by Beth

Quote:

Originally Posted by Beth1708

Long article -- The Concept of Gamma-Glucose **Here is the base page for the page Beth linked to.**

I have concluded that Benjamin P. Sandler, M.D. created the idea of Gamma-Glucose as a molecule that would explain the fall in oxygen absorption in some experiments on people. It is sort of like the concept of "ether" that was first used to explain the transmission of radio. Note, that like ether, Gamma-Glucose could not be isolated. The explanation for that being that is was so reactive.

Quote:

Originally Posted by Beth1708

If I were forced to guess, from some of what I have read on what Dr. Sandler was concerned with understanding, the "missing" substance he needed to explain the oxygen absorption quandary was ketones. Ketones are made from fat and are "burned" easily by most cells, even preferred by some. So the "preference" for ketones may have been what caused Dr. Sandler to say "glucose in the diet can't be burned as well."

Very nice Thank you ! Ron

Thanks Larry and everyone who has posted on this. I do need a little translation and really appreciate you putting your minds to the topic and your ideas out for others' benefit.

Dr. Thomas Seyfried: A Calorie-Restricted Ketogenic Diet Could Be The Cure For Brain Cancer (Episode 302)
It's worth listening to Thomas Seyfried's interview with Jimmy Moore.