Treatment implications of the Naviaux study (PNAS, August 2016)

[Biarritz13]

One has to remember that this study is looking only at plasma, and not trying to account for intracellular contents or activity. Having said that, it appears that DHA is high in most of us, while phospholipids, and especially sphingolipids, are low. One could go the expensive Garth Nicholson route, as has been suggested in the main thread, but one could also shift gears from fish oil to krill oil, which contains lower amounts of DHA and EPA that are apparently more bioavailable because bonded to phospholipids, which contain also some sphingolipids. I am no expert on this stuff, but it would seem an easy and inexpensive move.

Vegepa has 100% of EPA, no DHA and the reviews are very interesting :

http://shop.igennus.com/reviews.php?productid=16133

 

[helen1]

Who here can claim remission from the "methylation protocol"? I like many others here have tried it with no real change.

Others apart from Johnmac and ahmo appear to have done well with methylation. Here are some I've noted over the past 4 years:

stridor (did other things too to improve),
Idie (says recovered using freddd's protocol),
howirecovered (used methylation mainly),
greenshots (says 95% recovered via mainly methylation),
sherlock (freddd's plan),
Red04 (his wife actually - used mainly methylation)
caledonia (says much improved with methylation)

 

[PennyIA]

But this sentence can explain why some have been better or near a remission state thanks to methylation. No?

That's what I'm thinking...


I have gone into remission during methylation protocol. It doesn't last forever and I have complications (I believe because of not having a biochemistry background which means I'm probably not doing everything I need to).

BUT IT DEFINITELY DID NOT CURE ME.

I realize I'm taking something complex and tying it to something else complex - but it may help explain why some people do better with methylation treatment (cure or not, quality of life improvement is all I'm seeking while waiting for a cure).

1) If I were to try to stick a fictional number on the PERFECT amount of energy supplied to a person (bear with me).

Let's pretend that you EAT everything you should, do everything perfectly and have no toxins, viruses NOR a hypometabolic state of afairs.

Patient A Score = 1000

2) You have methylation defects (again, not everyone ill has these, but lets pretend patient A does....

And the current *rough* numbers I've seen is that depending on the severity of methylation defects you only absorb a percentage of the nutrition intake... so even if you are on the perfect diet with the perfect mix of nutrients, not all of those nutrients will go to energy production. How much? well.. jury is out right? But I've heard between 20% and 60%... let's stick with 30% so that we're on the conservative side.

Patient B Score = 1000 * (100 - 30 -- or 70%) = 700

3) Now you are exposed to a toxin (mold) or a virus (Epstein Barr, etc) or just about anything that would induce the TEMPORARY state of hypometabolic... and during this SHORT TERM - incoming nutrients are diverted from energy production to life preservation (if I'm understanding the study correctly)....

So, even if you get 1000 or get 700 in... some of that is no longer used for energy production. How much? no idea... but what if it's something like 50% (and I wouldn't be shocked if it's higher)... but lets stick with a small number - let's say 20% (again conservative side):

Score for patient A is now 800
Score for patient B is now 560

Now, let's face it - if you ate junk for one or two days and only GOT IN 560 or 800 'energy input'... your body adapts and you feel weak and ill - but you start eating better and it's not the end of anything.

If you are in a chronic hypometabolic state - well, you start FEELING HORRID. BUT... if you can INCREASE your score from 560 to 800 by methylation treatment - well, that might seem like an improvement, if not remission.

We still don't know enough to know if relapse/remitting is part of this scenario or what controls the on/off state of hypometabolic for us - but I don't think this precludes the fact that some people feel better on methylation treatment and others REALLY DON'T... and that it's because it's feasible that poor methylation (or toxin load or viral load) contribute to the overall net loss of energy.

NOTE: when I'm in 'remission' - I see myself at around 80% of what ought to be my normal; but PEM can still apply.

 

[Gingergrrl]

I believe that there are many people who have had some improvements from the methylation supplements, just that I was not one of them! And there is an equally large (or larger?) group of people who cannot tolerate these supplements no matter how hard they try. So I wouldn't want the new research paper to lead doctors to think that methylation supplements can "cure" or even help the majority of us vs. what I would call one "sub-group" (for lack of a better term).

 

[Sushi]

Others apart from Johnmac and ahmo appear to have done well with methylation. Here are some I've noted over the past 4 years:

I had a modest improvement.

 

[Rooney]

B12 injections took away my hand tremors. Adding folate took away my headaches. I'm still writing from a prone position though.

 

[Ben H]

Pushing B vitamins has never cured anyone and never will and it makes many severe ME/CFS patients worse. Disappointed to see that sentence in the paper.

Hey @Sidereal,

I think from what I have gathered so far, and is implicated in the study, it will require a multi-focal approach to treatment.

This may mean plugging/replenishing the metabolic shortfalls, and then using some treatment (antipurigenic?) to switch us out of this dauer-like state to access those resources.

So Naviaux isn't really just saying 'b vitamins' and that's that. I get where you are coming from however, totally, in terms of treatments that have been let downs, B vitamins being one of many for lots of people.

This is all just guesswork though, I may be totally wrong. But the study isn't really enough to tell us what to do right now. Especially as it seems 75% of metabolites results found seem unique to the individual, which will likely require an individual approach.


B

 

[Sidereal]

This may mean plugging/replenishing the metabolic shortfalls, and then using some treatment (antipurigenic?) to switch us out of this dauer-like state to access those resources.

So Naviaux isn't really just saying 'b vitamins' and that's that. I get where you are coming from however, totally, in terms of treatments that have been let downs, B vitamins being one of many for lots of people.

Thanks for your comments. I appreciate that he's not 'just saying B vitamins and that's that'; I wasn't trying to imply that. I disagree with the overall approach of replenishing these downregulated metabolic pathways, I'm afraid. If the hypometabolic state is adaptive/protective, as some have argued over the years, then switching off the dauer-like state may bring about an increase in functional capacity at the expense of killing us faster by means of conventional diseases.

 

[adreno]

If the hypometabolic state is adaptive/protective, as some have argued over the years, then switching off the dauer-like state may bring about an increase in functional capacity at the expense of killing us faster by means of conventional diseases

I am not recommending anything, but have personally become more functional as a result of B vitamins and other supplements (plugging metabolic holes). Will I die sooner because of this? Perhaps, but so far nothing dooming on the horizon, and I value my functionality.

 

[Sidereal]

I am not recommending anything, but have personally become more functional as a result of B vitamins and other supplements (plugging metabolic holes). Will I die sooner because of this? Perhaps, but so far nothing dooming on the horizon, and I value my functionality.

I think it's impossible to say without long-term follow-up studies of untreated people vs. those who tinkered with supplements and meds.

 

[L'engle]

I've had temporary improvements (lasting a day, needing constant reloading) from loading methylcobalamin as per Freddd's protocol but nothing near remission. I didn't experience any cumulative healing from it unfortunately.

 

[taniaaust1]

Incremental improvements in NADPH production could theoretically be supported by interventions directed at folate, B12, glycine, and serine pools, and B6 metabolism, however the safety and efficacy of these manipulations have not yet been tested in a rigorously designed clinical trial.

Ultimately, effective treatments for CFS are likely to be achieved by careful attention to nutrition, metabolism, triggers, stressors, and physical activity as an integrated system,

That is probably a very good start I think to things for many of us. In my case active folate forms and methyl B12 help a bit. (I didnt notice B6 helping me though). Getting my diet right eg finding out all my different dietary issues and then not having certain things helps me too.

i think any treatment on us should be integrated and we do need to know our triggers so we know what to avoid doing which makes us worst.

anyway, I think they are "half" on the right track. looking at these things.

When I collected peoples who had ME/CFS, their experiences with the B group vitamins, (I got responses on if any of the B vitamins were useful or not of 30-32 different people here), to my surprise I found that 3 out of every 4 people here (75%) had had a positive experience with one of the Bs. With around 50% of those here having a positive experience with one of the various forms of B12.

75% positive response (even if slight improvement) is an amazing response when one compares this to the response of other supplements and drugs we commonly try (there was nothing else which even come close to having this many say it helped). The issue is finding out which Bs will help us and what forms of them will help as it varies so much.

 

[taniaaust1]

I've had temporary improvements (lasting a day, needing constant reloading) from loading methylcobalamin as per Freddd's protocol but nothing near remission. I didn't experience any cumulative healing from it unfortunately.

I was like that with hydroxy B injections (I only got very slight brain improvement) but it would wear off after 3-4 days. I did those for about 2 years or so. (they were obviously helping thou even so as I could clearly feel the wear off).

I have had better improvement with methyl B tablets daily under the tongue and they did seem to start bringing possibly to me a more cumulative healing as long as I had my pacing and everything else right too.

This is an area I personally think does need a lot more study as something is helping many of us with this even if it doesnt cure.

 

[taniaaust1]

If there is one thing we have exhausted, it is B-vitamins.

B vitamins though no cure, they have helped many of us and from my study of over 30 different people at this website, I found it helped more of us then any other supplement or medicine (it was actually 75% of those I asked)

the issue is its different Bs for different people here and also even with something like B12, individuals can find they do well with one form of it but not the other or even get negative responses to some forms. There can also be like start up reactions (one of my first experiences with B12 was bad, I ended up looking like someone who had taken acid fortunately I had been warned about start up reactions so continued it. This vitamin esp if in a certain form of it is helpful to me).

So its not one size fits all with this stuff and any good study done in this area would also need to focus on working out which Bs the person did well on and which forms eg hydroxyl or methyl B12.. and then only when they have that info for each individual to then compare with a control group. Doses for patients may be quite individual too eg B12 injections, some with ME/CFS found they needed daily, in my case it was every 3-4 days.

I dont think one could do a good study on this with just giving everyone the same, this treatment needs to be tailored for each individual. I do not think this has been well researched.

 

[PennyIA]

I dont think one could do a good study on this with just giving everyone the same, this treatment needs to be tailored for each individual. I do not think this has been well researched.

Agreed. I'm hopeful that the metobolics study that explains that 75% of the markers were unique and distinct to individuals and calls out that to address those, you'd have to have individualized treatments is a light that may help us on our way to understanding who shouldn't bother even trying the B's, who should stay away from methylolate, who should load it up, etc.

 

[J.G]

The methylation cycle is linked to the production of NADPH, which was found lacking in the study. This has been suspected for a long time. The problem with adaptive syndromes like ours seems to be that they are beyond remedy using simple nutritional approaches, because the body keeps reverting to the newfound, now preferred (mal)adaptive homeostasis.

Fully agree with you. Discounting placebo effect, the 'altered state' potentially explains why for so many PWME certain combinations of supplements seem to bring brief improvement before losing their effectiveness. The supplements are quickly subsumed under pre-existing altered state metabolism, and insufficient by themselves to drag the body out of it.

 

[alex3619]

We used to discuss this kind of thing before, including even here on PR I think. The usual analogy was in terms of chaos theory, and strange attractors. An attractor is a central point which a system is always tied to, a central tendency about which it revolves, though both those analogies are only half right. If something changes and that attractor is moved, then it shifts to a new stable state. You might push the system a bit, and it will change, but unless the attractor moves to a position that is healthier you have not done anything much.

A stable dynamically enforced system will attempt to revert back to its prior state if its perturbed. If there is some kind of loop between various sensor mechanisms and other mechanisms enforcing a suppressed metabolic state, then its possible that certain things might even drive the health down further. I think aerobic exercise might be a candidate there. Symptomatic relief would be more about playing a tune on the metabolism, rather than a cure.

I suspect full cure will require understanding of both the on mechanisms and the off mechanisms for a suppressed metabolic state. We now have some idea what to look for, but its not clear we have found it yet. Latent pathogens, toxins, etc., are not ruled out, but they are not ruled in either. We need more data.

I think we will have treatments before full cure, though just treating some patients might lead to a cure, and Rituximab might be the first agent to do that. Ampligen will likely be useful as treatment not cure. Though I do have to wonder, if you start mixing immune modifying agents and nutrients, what will happen?

 

[mermaid]

It's taken me a long time, but I have become more functional this year by fixing or managing my worst symptoms - it had become a kind of vicious circle in that I felt too ill to do anything much. I now don't feel ill mostly, and have done a reasonable recovery even from a detached retina operation 4 weeks ago.

I have been taking most of the methylation supplements plus others for quite a long time, see a medical herbalist, have fixed my diet as well as I can, and try to pace (not very well). The problem that remains is presumably mitochondrial as I lack stamina and cannot walk or exercise as far as normal people. I especially find standing for more than a few minutes very difficult (not dizziness exactly, just energy draining which I guess is the orthostatic intolerance).

 

[J.G]

@alex3619 Yup. Finding a full cure for ME might require jolting the body from the 'dauer' stable equilibrium, as Naviaux et al. put it, to a normal stable equilibrium. Finding a central trigger for ME, i.e. understanding why the body goes into an altered state, might yield clues on how to reverse this change. I think this is precisely what a group of scientists - can't remember whom, exactly - are trying to do: reverse-engineer ME in vitro and subsequently try and undo the process.

 

[loops]

Are they still thinking in terms of anti purinergic therapy do you think? Suramin etc
(Have to say I'm in awe.....there are some clever people on PR. Imagine what they'd be like without brain fog!!!)