Carbs and Cancer

I've just finished reading an interesting review article on the relationships between carbohydrate intake(sugar!) and cancer incidence and metabolism. There are some important lessons here and worth giving serious thought to. For example:

Cancer, which might be considered a disease of civilization, has consistently been reported to be very rare among uncivilized hunter-gatherer societies [1-4].

... 

Data from 229 hunter-gatherer societies included in the revised Ethnographic Atlas indicate
that hunter-gatherer diets differ from typical Western ones in basically two aspects: first, a
strong reliance on animal foods (45-65% of energy or E%) and second, the consumption of
low-GI plant foods such as vegetables, fruits, seeds and nuts [7]. This is consistent with stable
isotope studies of human fossils [8, 9].

Full details of the paper overleaf.


Paper details:


Is there a role for carbohydrate restriction in the treatment and prevention of cancer?

Nutrition & Metabolism 2011, 8:75 doi:10.1186/1743-7075-8-75

Rainer J Klement (rainer_klement@klinik.uni-wuerzburg.de)
Ulrike Kammerer (kaemmerer_u@klinik.uni-wuerzburg.de)



Website download full paper:
http://www.nutritionandmetabolism.com/authors/instructions/

Abstract

 Over the last years, evidence has accumulated suggesting that by systematically reducing the
of cancer, and that proliferation of already existing tumor cells could be slowed down. This
hypothesis is supported by the association between modern chronic diseases like the
metabolic syndrome and the risk of developing or dying from cancer. CHOs or glucose, to
which more complex carbohydrates are ultimately digested, can have direct and indirect
effects on tumor cell proliferation: first, contrary to normal cells, most malignant cells depend
on steady glucose availability in the blood for their energy and biomass generating demands
and are not able to metabolize significant amounts of fatty acids or ketone bodies due to
mitochondrial dysfunction. Second, high insulin and insulin-like growth factor (IGF)-1 levels
resulting from chronic ingestion of CHO-rich Western diet meals, can directly promote tumor
cell proliferation via the insulin/IGF-1 signaling pathway. Third, ketone bodies that are
elevated when insulin and blood glucose levels are low, have been found to negatively affect
proliferation of different malignant cells in vitro or not to be usable by tumor cells for
metabolic demands, and a multitude of mouse models have shown anti-tumorigenic properties
of very low-CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucose
metabolism characterized by insulin resistance and may profit from an increased protein and
fat intake.
In this review, we address the possible beneficial effects of low CHO diets on cancer
prevention and treatment. Emphasis will be placed on the role of insulin and IGF-1 signaling
in tumorigenesis as well as altered dietary needs of cancer patients.
Key words: Ketogenic diet, cancer, review, low carbohydrate diet, cachexia, insulin,
insulin-like growth factor 1 (IGF1)

amount of dietary carbohydrates (CHO) one could suppress, or at least delay, the emergence

 I have repeated read that cancer is rare in animals and hunter gatherers. I have never looked at the evidence and take it on faith that all these researchers are correct. What might be interesting is to compare cancer rates of wild species with long lived domesticated animals, including pets and milking cows. As household pets are now typically overfed, under exercised, and stay indoors (no sunlight exposure), and live much longer than in the wild I would expect to see higher cancer rates in household pets.

Damn the Carbs, Burn the Sugar! 

A diet high in carbohydrates has been consistently associated with metabolic syndrome, diabetes, cancer, and dementia. Here is a fascinating observation from the paper:

Treating diabetic patients, A. Braunstein observed in 1921 that in those who developed cancer, glucose secretion in the urine disappeared.

It is now well established that cancer cells rely very much on glucose as their principle and perhaps only energy source. Carbohydrates cause big sugar spikes in our bloodstream which in turn induces inflammation, so the increasing emphasis on carbs and sugar in our diet is very much elevating the risk of cancer in modern societies.

The Warburg Effect

Cancer metabolism is very much about glucose. We can be assured of that. This is commonly referred to as the Warburg Effect, first proposed by Otto Warburg and others in the 1920's. The Warburg Effect is essentially a ubiquitous feature of tumours, though I suggest that it is a consequence of tumour growth rather than a cause of tumour growth.

The nutshell is this:

1. Most cells generate the "energy molecule", ATP. For an excellent introduction see this page. 
2. In cancerous or precancerous cells ATP is generated through a much less efficient process known as glycolysis. This page offers a somewhat complex introduction.  It would appear that glycolysis arises as a consequence of tumour growth. 
3. Note though that we do not fully understand why glycolysis replaces mitochondrial ATP production. This paper puts forward a number of hypotheses for the emergence of glycolysis. Please be aware that if anyone tells you why glycolysis occurs so frequently in cancerous cells that person is probably wrong. I suspect the path to glycolysis dependence will be varied according to the microenvironment and other factors.
4. The instantiation of glycolysis dependent ATP production appears to promote tumor growth and tumourigenesis. 
5. Glycogenesis promotes acidification of the microenvironment by generating lactic acid and H+ ions. This has important implications for tumour survival because ... 
6. Acidification of the microenvironment further induces apoptosis in normal parenchymal and stromal cells [74, 75] and therefore provides a strong selective growth advantage for tumor cells that are resistant to low pH-induced apoptosis [76, 77].

The last point highlights why many people of alternative medicine inclination stress the importance of alkalinity. However, whether or not drinking alkaline water will have any significant impact on the microenvironment seems problematic to me because the constant stream lactic acid and H+ production will probably mitigate against that. What would be interesting is the direct application of alkaline promoting agents to the tumour.

We still do not understand the emergence of the Warburg Effect. I'll take the easy way out: many paths to the Warburg Effect and this paper does a good job of outlining those potential pathways.

Sugar, Insulin, Insulin Growth Factors.

Growth factors are often regarded as "youth hormones". That is a very dangerous way to describe growth hormones yet only today on Mercola's website the naughty doctor did just that. Elevated growth hormones and their receptors are a key feature in many cancers. As we age growth hormone levels decrease markedly. Sugar and carbs give growth hormones a boost. Caloric restriction very much impedes growth hormone function either through reducing its production or increasing the production of its binding protein IGFBP. Caloric restriction should be regarded as a good personal strategy to treat cancers. As this article states CR may not even be necessary, simply switching to a ketogenic diet  may be a better strategy because ketone bodies and cancers do not get on well together ... .

The relationship between sugar, insulin, and growth factors is a cardinal aspect in understanding carcinogenesis. I suggest that any cancer patient give serious consideration to cycling through fasting and\or a ketogenic diet. This paper highlights a number of studies in this area but unfortunately human studies are very limited. That is a neglect that needs to be corrected. As the authors state:

These findings again underline the importance of controlling blood sugar and
hence insulin levels in cancer patients. Dietary restriction and/or a reduced CHO intake are
straightforward strategies to achieve this goal.

Conclusion

If you are familiar with the relevant literature this paper is worth a read. Contrary to the opinions of some conventional medicine is not constrained by Big Pharma to the extent that these novel approaches are ignored. Where there is a problem is that because there is no money in these novel approaches little research is devoted to the issue. That needs to change. There is, at the research level at least, a very active investigation across a range of strategies to address cancer. That is exactly as it should be because cancers are very diverse in their metabolism, mutations, and formation.