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Thursday, 6 December 2012

Rich Van Konynenburg R.I.P. - Methylation and Glutathione.

I was saddened to learn of the death of independent researcher Rich Van Konynenburg PhD. last month.
Rich was a researcher into the causes and treatment of chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) and his outstanding contribution was to grasp the importance of glutathione and the methylation cycle to this disease, then adapt the autism research of Dr Amy Yasko to suggest the concept of methylation cycle blocks and deficient antioxidant protection from glutathione as its characteristics.
There is a vicious cycle mechanism; glutathione protects B12 from the denaturing effects of, for example, mercury or peroxynitrite, and B12 is the co-enzyme that transfers methyl groups to homocysteine, creating SAMe (AdoMet).

This hypothesis struck me as obviously relevant to hepatitis C. Liver disease is produced experimentally by dietary deficiencies, i.e. a diet deficient in choline (a methyl donor) and/or methionine (the source of both SAMe, a methyl donor, and the cysteine moiety of glutathione). Deficiency of selenium will cause hepatic necrosis, and selenium is the co-factor for those enzymes that use glutathione to remove free radicals.

I contacted Rich Van Konynenburg by email and corresponded with him for some time. Re-reading my emails they are breathless and prolix, and there were too many of them, and Rich's replies are detailed and not at all dismissive. He corrects my mistakes gently and encourages my interest.
Rich was like the hedgehog in Isaiah Berlin's parable who knew one thing but knew it very well. He knew the methylation cycle and transsulfuration pathways (the parts of biochemistry concerned with the non-protein functions and metabolism of the essential amino acid methonine) intimately, the proteins and genes involved, the polymorphisms that influenced metabolism one way or another, and how this related to various diseases, especially CFS/ME, autism, and Lyme disease.
The methylation cycle and transsulfuration pathways are a good place to start if you are interested in biochemistry, because their simplicity belies their overall importance to health. There are only 3 vitamins required (folate, B12 and B6) and 3 minerals (magnesium, molybdenum, and selenium), yet the products of the system include many of the chemicals popular as energy supplements; carnitine, creatine, phospholipids, taurine; and of the neurotransmitters, besides the role of glutathione and taurine in bile production and of both methylation and glutathione in neutralizing toxins.

Methylation Cycle

This site gives a link to Rich's many papers; and here is the wiki page on which the hypothesis was expounded and referenced in all its detail. Anyone familiar with the work of Chris Masterjohn at Weston A. Price will know about the importance of glutathione and choline in the diet - here is the repository of the technical and clinical data that underlines that importance.
Both Rich's help, and the example provided by his very existence as a respected independent health researcher, were of the utmost encouragement to me as I strove to educate myself. His scrupulous accuracy and honesty - exemplified by his case reports of adverse reactions to his suggested treatment protocol - set a high standard for others to aspire to. My regret is not being able to catch up with him again before his sudden death. 


john said...

Hi George,

I was interested in your comment on Hyperlipid and responded with "George,

Lactate I think is correlated with glucose metabolism and carbohydrate intake, along with glycogen amount in muscles and muscle fiber type.

What are your practical ideas from your comment, or what do you think that quote about BHB, lactate, pyruvate, and glucose reveala about diet? "

Would you expand a bit on your idea?

George Henderson said...

At the moment it seems more of a mnemonic, something that make a useful educative soundbite.
In metabolic syndrome there is an excess of glucose and fatty acids in circulation. Would converting some of the glucose to lactate (by exercise) and/or some of the fatty acids to ketone bodies (by intermittent fasting and/or carbohydrate restriction) restore metabolic flexibility? This seems to be what happens.
What mechanisms might account for this in the case of lactate?

If nothing else it is a simple way to bring the benefits of exercise into the tent of basic metabolism, so is deserving of some investigation.

Incidentally, lactate is how muscle glycogen can be accessed by the brain. That amount that escapes into circulation and is not re-used by muscles can be converted to hepatic glycogen, or perhaps used directly.
Does lactate usage require less insulin overall?
Interestingly, the lactate receptor GPR81 is related to the ketone body receptor GPR109a.

john said...

I think Taubes' book tarnished the sentiment toward exercise because he seemed (I don't know if he's changed at all) to view it as nothing more than a way to burn calories. Perhaps that is true in the case of something like jogging, where long term effects are even negative. I think higher intensity workouts are clearly positive.

Are you familiar with It is a nice place, like a database, for reading on ...brain fuels.

George Henderson said...

I think Taubes had exercise as great for fitness, in moderation, but lousy for weightloss. But most things are lousy for weightloss in controlled studies that isolate them - even low carb, though it comes out best, isn't all that. I think you're right, that Taube's choice of words has caused people to dismiss exercise a little - but there is an effect of true inactivity, so we should be factoring it in again.
Thanks for the link; interesting!

George Henderson said...

There's a paradox - if exercise is useless because it only burns calories, why should losing 300 calories a day from metabolic advantage be any different from exercising or fasting that much?

john said...

That's a good question. Perhaps that's why it's productive to try to understand physiology of fat storage and appetite, as opposed to worrying about calorie number itself. Discussions of calorie threshholds (after which all calories "just get stored as fat") and setpoints aren't very insightful.

George Henderson said...

My default position is that ketosis corrects disordered appetite in the same way it corrects say epilepsy. The neurons that govern the appetite for food and the instinct for activity - that co-ordinate the two - are damaged (which can also play out as hyperactivity) and if anything can fix them, ketones can. Therefore calorie loss by ketotis is more therapeutic than by other means IF the problem is neurological (Peter's "icepick").
But only by association.

phooey said...

Hi George,
Have you ever looked into Tauroursodeoxycholic acid (TUDCA)for liver issues? There is not a lot of research but what I have found looks interesting.


George Henderson said...

No, I haven't seen that before, but supplementing taurine can be good, and this will help you make TUDCA.
Good especially when the problem is in the gall bladder, i.e. elevated bilirubin, or characteristic gall bladder-related right quadrant pains.
In which case dandelion root should also be used.