Thursday, 8 March 2018

L-Carnitine, ketolytic enzymes and therapeutic ketogenic diets for cancer management.

L-Carnitine plays an absolutely vital role in the metabolism of fatty acids.

Mo Farah is recently, somewhat controversially been pruported to have had an injection of L-Carnitine before the 2014 London Marathon for performance gains. It is worth noting that Mo Farah is an endurance athlete, so fat is the predominant fuel source. Fat oxidation rate is high so if you can sustain this for a longer period of time you can improve limits of exhaustion.

Carnitine shuttle (1)
This IV administration by Mo Farah is now being seen by the media in this country as 'cheating within the rules' with increased scrutiny recently of 'marginal gains' in athletic performance and sport in general after the cycling 'scandal' with Team Sky riders making the most of Therapeutic Use Exemptions (TUEs) that are known to improve performance for endurance athletes.

What helps athletes often has great potential for cancer patients- ie. infusion of nutrients, certain drugs, nutritional supplements, hyperbaric chambers, cold induced thermogenesis, infrared saunas, etc.

It is interesting....

Like Mo Farah I also take L-Carnitine because it ensures efficient transfer of long-chain fatty acids to mitochondria for subsequent β-oxidation. The brain has an abundance of mitochondria and if you subscribe to the mitochondrial defect theory of cancer as I do its kind of a no brainer (pun intended) that you would want to make the most of everything you can do to do try and restore mitochondrial function here. This can potentially be very beneficial for ensuring that ketone bodies produced during fasting, or fats on the ketogenic diet actually get used so that we can attempt to attain more healthy mitochondria.

This is what I take
There is exhaustive evidence showing how supplementation with L-Carnitine could benefit cancer patients, mostly for reducing general fatigue during chemotherapy (2) but also for normalising lipid metabolism for more general health (3). Anti-dementia effects have been proposed and suggested when co-administering L-Carnitine with medium chain triglycerides (MCTs) and other agents (5, 6). A higher rate of absorption would result in rapid perfusion of the liver, and a potent ketogenic response.

Perhaps an important consideration: 

If you are thinking of taking this as a brain cancer patient however, it may be worth some exploration to see if your tumour has increased activity of ketolytic enzymes to see if it can use fats to proliferate. You can ask about this from histological findings. 

Ketone body ketolytic enzymes to assess expression of include (4): 

Succinyl CoA: 3 Oxoacid CoA Transferase (OXCT1)
3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and BDH2) 
Acetyl-CoA acetyltransferase 1 (ACAT1) 

This can be the case in more aggressive tumours rather than typically lower grade, more solid tumours. I suspect this may be because the tumour is more diffuse, and as such the cell membrane may lack integrity and become more permeable. This is a theory I have based on research looking at alterations of membrane integrity and cellular constituents in neuroblastoma and glioma cells (8). 

I could be completely wrong with that theory, but either way there is often an overexpression of Fatty Acid Synthase (FASN) in high grade gliomas (7), a key lipogenic enzyme in glioma stem cells (GSCs), as well as other important metabolic enzymes, meaning aggressive tumours will try to use whatever they can to grow and thrive and are excellent at adapting to use alternative fuels when you restrict main substrates. These tumours will use glucose, amino acids, fats and nucleic acids for energy, and while the demand will be different for each, as the tumour becomes more aggressive the amounts will change and it becomes more and more resistant to even the most aggressive treatments. 

6. Odle, J., 1997. New insights into the utilization of medium-chain triglycerides by the neonate: observations from a piglet model. The Journal of nutrition127(6), pp.1061-1067.

1 comment:

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