Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

Cancer, ketones, dichloroacetate

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I wrote a very long essay on cancer last year but took it down, and I really need to get it back online. In it I mentioned how a ketogenic diet has shown a lot of promise in treating cancer. Eades posted a couple of items on it last September.

The theory behind it is that cancer cells have defective mitochondria that make them 1) unable to burn fat and 2) forced to burn glucose through anaerobic fermentation, producing lactic acid as an end product.

This is copied directly from the marvellous New Scientist magazine:

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020).

Michelakis suggests that the switch to glycolysis as an energy source occurs when cells in the middle of an abnormal but benign lump don’t get enough oxygen for their mitochondria to work properly (see diagram). In order to survive, they switch off their mitochondria and start producing energy through glycolysis.

Crucially, though, mitochondria do another job in cells: they activate apoptosis, the process by which abnormal cells self-destruct. When cells switch mitochondria off, they become “immortal”, outliving other cells in the tumour and so becoming dominant. Once reawakened by DCA, mitochondria reactivate apoptosis and order the abnormal cells to die.

“The results are intriguing because they point to a critical role that mitochondria play:

they impart a unique trait to cancer cells that can be exploited for cancer therapy,” says Dario Altieri, director of the University of Massachusetts Cancer Center in Worcester.

The phenomenon might also explain how secondary cancers form. Glycolysis generates lactic acid, which can break down the collagen matrix holding cells together. This means abnormal cells can be released and float to other parts of the body, where they seed new tumours.

DCA can cause pain, numbness and gait disturbances in some patients, but this may be a price worth paying if it turns out to be effective against all cancers. The next step is to run clinical trials of DCA in people with cancer. These may have to be funded by charities, universities and governments: pharmaceutical companies are unlikely to pay because they can’t make money on unpatented medicines. The pay-off is that if DCA does work, it will be easy to manufacture and dirt cheap.

Paul Clarke, a cancer cell biologist at the University of Dundee in the UK, says the findings challenge the current assumption that mutations, not metabolism, spark off cancers. “The question is: which comes first?” he says. Cheap, safe drug kills most cancers

Acetic acid is basically vinegar, and one of the major ketones produced during low carbing, fasting, or weight loss. Wiki’s entry on Dichloroacetic acid:

Dichloroacetic acid (systematic name dichloroethanoic acid) is an analogue of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. It is prepared by the reduction of trichloroacetic acid.

The chemistry of dichloroacetic acid is closely related to halogenated organic acids. It is a member of the chloroacetic acids family.

Dichloroacetate stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting the enzyme pyruvate dehydrogenase kinase (Stacpoole PW. 1989; PMID 2554095). As such it decreases lactate production by shifting the metabolism of pyruvate from glycolysis towards oxidation in the mitochondria. This property has been used to treat lactic acidosis in humans (Stacpoole et al, 1988; PMID 3337517).

In recent experiments at the University of Alberta, dichloroacetate has also been shown to regulate and restore normal metabolic functions in damaged mitochondria. This has proved particularly interesting in cancer cells, which do not self-terminate upon detecting abnormalities due to damaged metabolic functions. Tiny doses of dichloroacetate shrunk breast, brain, and lung cancers in both human and rat specimens.[1] Dichloroacetic acid

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Written by alienrobotgirl

19 January, 2007 at 10:58 am

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