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10 years later, what is the current consensus on the validity of the Rich Van Konynenburg documents?

I have been reading them, after sending the web page to the Kindle app, and there's a massive wealth of knowledge there. Also, it's the most accurate explanation I've found for how my wife symptoms developed and how they've been helped by glutathione and B12.

However, 10 years later, there are still many people with CFS.

So, I wonder what is the current view on Rich's ideas after 10 more years of research studies and N=1 self-studies by members of this forum.



Senior Member
Most research doesn't get followed up due to lack of funding. There is a chance the answer to at least treatment has already been released but it never got followed up. But supplements have not proved to be universally useful yet and the answer where it's easy to get is likely not to be the answer for most people.


Senior Member
So, I wonder what is the current view on Rich's ideas after 10 more years of research studies and N=1 self-studies by members of this forum.

There are far fewer people interested in Rich's ideas these days. And if you look at this survey, only 3% of patients reported major improvements from the methylation protocol. Although 28% obtained more minor improvements, so it may still be worthwhile trying the methylation protocol.

Note thought that some of the discussion you read about the methylation protocol borders on pseudoscience. For example, people talk about "methylation blockages", and they promote this notion that if you can only just overcome your blockages, you are going to fall into much improved health. So then people spend months or years trying to surmount their mythical methylation blockages.

Yet I have never come across anyone on this forum who initially failed to get any benefits from the standard methylation protocol detailed by Rich, and then only later succeeding in getting it to work after identifying and addressing one of these proverbial "methylation blockages".

But certainly some ME/CFS patients do report benefits from vitamin B12 injections, and/or from active folate. But whether this relates to the effects of these supplements on methylation, or is due to some other metabolic effect the supplements have, is not known.

In my case, if I take methylfolate daily, even doses as low as 100 mcg, I find that after some days it starts to cause an overstimulated mental state (such overstimulation is believed to be a result of overmethylation), as if I had drunk too much coffee. In this overstimulated state, it can seem as if your ME/CFS is better, because the stimulation gives you energy and mental focus.

However, I suspect I would get the same energy and focus from a stimulant drug. So I wonder if some of the benefits that patients report from doing the methylation protocol might simply derive from being mildly overstimulated by overmethylation, rather than increased methylation actually addressing any root causes of ME/CFS.

I also notice brain fog improvements from methylcobalamin, in the form of Dr Greg Russell-Jones's B12 transdermal oils (which deliver more B12 into the bloodstream than even injections). This is not due to an overstimulation effect. Somehow this B12 improves my brain fog a little.
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Senior Member
East Coast, USA
Homocysteine is involved in the inflammation/immune balance. Homocysteine activated NLRP3 inflammasomes in THP-1-differentiated macrophages and promoted subsequent production of IL-1β and IL-18 in macrophages, which were blocked by NLRP3 gene silencing or the caspase-1 inhibitor Z-WEHD-FMK https://pubmed.ncbi.nlm.nih.gov/28394319/ High homocysteine following folic acid or vitamin B12 deficiency also down-regulates peroxisome proliferator-activated receptor (PPAR) expression. Homocysteine has recently been found to be a competitive inhibitor of the nuclear transcription factors: Peroxisome proliferator activated receptors (PPARs) alpha and gamma https://link.springer.com/article/10.1186/1475-2891-3-4

Vitamin B12 involved with methylation is inactivated as a consequence of high itaconate (itaconate shunt). "itaconyl-CoA is a cofactor-inactivating, substrate-analog inhibitor of the mitochondrial B12-dependent methylmalonyl-CoA mutase (MUT). Our work de-orphans the function of human CLYBL and reveals that a consequence of exposure to the immunomodulatory metabolite itaconate is B12 inactivation." So yes there may be 'blockage" https://pubmed.ncbi.nlm.nih.gov/29056341/ Glutathione appears to be involved with B12 conversion. Also B12 appears to react with superoxide when glutathione is depleted causing further reduction. This may happen with ongoing inflammation or infection as zinc uptake is lowered and further becomes unavailable to utilize and is needed as a glutathione cofactor. https://forums.phoenixrising.me/threads/sterile-methylcobalamin-powder.90523/post-2441209 Perhaps the added methyl B12 frees glutathione from depletion which then not only helps with superoxide but then becomes available again for the other functions.
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