Experience with LDN?

When you put it in those terms I’d say crossovers need to be out definitively in ME because of the way that PEM accumulates - then hits after 6mnths of just pushing your boundaries to the limit (and getting away with it … then not .. boom)

you can kid yourself a regime of whatever is making you better because you get the ‘ability to do’ or walk the tightrope but that’s not really ‘tackling ME’ but ‘IS ME’ (and I think where much of the medical profession is still stuck - because even patients need years of living doing this same false hope mistake to realise ).

to me what would/should be really accurate is the plain ‘a year on’ comparison of groups - with yes good measures to that.


Just as I think the public don’t get that PwME would have walked through hot coals of hell with GETs hurt doesn’t equal harm for the promise of that having an endpoint to their disability. Or even just a ‘chance’ of that being worth the effort. BUT Anyone voluntarily signing up would have asked from a medical professional one question alone: will/could it make me worse?

And I almost have to remind myself of that too when looking at measures.

 

The difficult thing is that the weeks where I’m actually worse and going downhill from having overdone things by no choice aren’t necessarily’less active’ because PEM affects my ability to get good rest (I’m already severe and doing little do the next stage is pain and having to ‘rest to get good rest’.)

If sensible patterns were being used and looked at not just snapshot then maybe better but I’d also add in a function measure for essential things like showering (how often, what help, how long and how much rest needed after before dressing) or tooth brushing in order to triangulate - with a proviso that a decline in those latter 2functions is likely to mean decline even when simultaneously ‘activity data’ seems like their body is more ‘active’

 

Yes, they say in the paper they didn’t measure ESR after treatment which is a huge error, so I guess which is why the follow up paper.

 

I've tried LDN and found it had a useful effect and seemed to work on a deeper level than other treatments I've tried, but it was only a temporary improvement in my case. Once I'd carefully worked up to a therapeutic dose, which started around the 2.5 mg range and above for me I noticed reduced inflammation and better cognitive function. This treatment response lasted for maybe 2 or 3 months before it tailed off. Eventually I started getting issues with dry skin and sinuses that I identified as side effects from the LDN, so I reluctantly stopped treatment. The side effects resolved and there was no loss of function from stopping, so I decided in my case I was overall better without it but I'd be willing to try it again at some point.

One point I'd like to make is that the form and supplier of LDN could be important. The syrupy liquid version made up by a pharmacy very experienced in compounding LDN worked best for me, see my post #3 here:
https://www.s4me.info/threads/trial...ens-hospital-health-centre.28368/#post-426494

 

Here are the links to Prof Theoharides studies.

https://me-pedia.org/wiki/Theoharis_Theoharides

Prof Theoharides spoke at The IIMEC13 Anne Örtegren Memorial Lecture.

https://www.youtube.com/watch?v=HNNPsZlDTEQ

 

I cannot see any results for controls in the cytokine paper?

 

I use these -
http://www.ldnnow.com/ - Jayne Crocker is from the UK and is contactable. I would think she would be very helpful.
https://www.ldnscience.org/

The other admin for the ME and Fibro facebook page is a PHD Medical Biologist. I have asked him if he would be happy to gather some evidence for you or talk with you if needed.

Jarred Younger has been trying to get funding for dextro for several years.

 

Googled "Jarred Younger + dextro" and found that --naltrexone ---- dextro naltrexone.

 

The ldnnow website says:

"LDN is not a miracle drug. It is a drug that implements the biotherapy approach to medicine, which is all about artificially stimulating the bodies own defences and systems in order to restore control over systemic diseases. This control is how most people remain clear of these diseases in normal health. The immune system we have has evolved over billions of years and does many jobs far better than our modern, symptom relief drug culture ever can." LDNNow

About Us:-
LDNNow are a political/pressure group of individuals dedicated to getting Low Dose Naltrexone (LDN) accepted into modern medicine and dedicated to the myriad of uses it is believed it shows benefit for. These uses include autoimmune diseases and many cancers (cell proliferative diseases).

This looks like quackery to me. I have never heard of a 'biotherapy approach'. The text is highly misleading and likely to make people turn to unproven therapies when they might get genuine help - particularly in the case of autoimmune disease and cancer. LDN has nothing to do with either as far as I am aware.

 

If the immune systems does things better than drugs, why offer a drug?

 

I don’t think that low ESR’s are necessarily the case. Cort’s report in HR in 2019 on “clumpers and sliders” discus Ron Davis and Dr Bella Chheda’s results, and the results of the biobank study -

“As an infectious disease doctor, Dr. Bela Chheda had run hundreds, probably thousands of ESR or sedimentation rate (SED) tests prior to working on ME/CFS. She ordinarily encountered increased sedimentation rates in her patients with infections, but then came ME/CFS – a disease triggered by infection which many people assume is inflammatory in nature. (ESR tests, it should be noted, do not pick up all kinds of inflammation.) The ESR or SED rates in many of her patients, though, were not just low but bottom of the barrel low (usually 2). (She thought the reason she didn’t see even lower numbers was that the test probably wasn’t sensitive enough.)

In fact, so many people with ME/CFS had very low sedimentation rates that she began to think of it as a kind of non-specific biomarker and wondered if something different might be going on in her patients with normal or higher ESR rates.

Chheda’s anecdotal reports appeared to jive with Ron Davis’s finding of reduced SED rates in his Stanford red blood cell deformability study.

But then came, surprise, surprise, a very large British Biobank study which found normal ESR rates (median=5) in more severely ill patients and slightly increased ESR rates (median=7) in less severely ill patients.

Another seemingly consistent finding in ME/CFS went to pot! Not able to explain the differences that are showing up and still hanging on to my consistently low SED rates (they must mean something), here’s a poll with a twist to add a another slice to the data. Using Dr. Natelson’s supposition that people with ME/CFS differ from people with ME/CFS and FM, the poll will be divided up into three categories”:

 

http://ldnnow.com/48501/90412.html

References: at the link
http://ldnnow.com/48501/90512.html

 

https://www.facebook.com/LDNNow

 

Yes, but although I haven't read through all of the text put below that, the beginning bit is complete nonsense. Just make believe.

 

I have read through. The information is grossly misleading, as well as being incoherent in places. I would assume that if this was written in the context of any commercial venture it would be illegal on trades description grounds. I actually think it should be illegal to put out such misleading documents in any circumstance. We are not told who the author is, as far as I can see. I strongly recommend that it is removed, for the sake of patients who may be misled.

 

I think we are in agreement that the residual/longer term measures are needed - ie 1yr on. And that the 6mnths on from treatment is the black box. ie 'condition 4' is the most interesting of those listed below

I was under the impression in this instance placebo ergo double-blinded would be made hard by the side-effect/dosing issues for LDN. But we need a control. And objective measures in that context are vital.

It's just that condition 3 below only adds benefit if blinding to control for placebo possible/as a placebo? , and without that then if we are looking at how we could interpret the possibilities

But it still leaves questions/interpretation in a way having 3 straight groups of 1yr control, 1yr treatment, 6mnths treatment--> 6mnths control might elucidate more? With measures at start and finish of each 6mnths for all groups.

But then I guess any 'placebo' might be the other way in as far as one group stops treatment half-way through (which they would anyway) but at least we'd have the 'staying on/off the drug' graph to compare it to?

I can see why it gets really hard if you have things like abifily where people have to take breaks vs something that 'might fix upstream before work downstream or vice versa' ergo take time for real effect to work vs 'stimulant category' type treatment that focus on helping get thru fatigue and crashes short-medium but don't treat underlying issue.

My brain is hurting from trying to work out the possibilities, so I might have got it wrong below?


Maybe - if we are working on blinding/placebo (trial effect) being impossible and ergo focusing on objective measures, then switching to: control for 1yr, treatment for 1yr, treatment 6mnths-->no treatment 6mnths. Basically taking all the measures at 6months of below but swapping out the control--> treatment for

I'm trying to 'game out' the possibility of if say 80% of patients were 'performing' 20% higher on treatment you'd have measures of:

1. placebo/control 6mnths - no difference

2. treatment 6mnths - 20% more activity more activity between start and finish

3. treatment (after placebo/control) 6mnths - 20% more activity between start and finish

4. 6months on from stopping treatment/placebo 6mnths after treatment 6mnths: which to me isn't the same as placebo in the context of ME/CFS. Because it is 'after having: both had treatment for 6months and done 20% more activity for 6months' + 'stopping treatment'


The bit I'd be most interested in is that last group 4 - to be reassured it isn't like many other treatments which make you think it is helping because it allows you to 'perform' by pushing your boundaries more for a while. But people might be tempted to look at 'treatment arms' and their start-finish differences.

But does that group 4 - if people crash and is the least active group - tell us that stopping treatment doesn't work, or that the treatment leads to a crash around 6months, 7mnths, 8mnths?

Or as Jonathan mentioned - if it's a drug that works, but the benefits are more obvious over time for various reasons that might be possible with ME - then that is the most active 6months?

Or - if somewhere in-between half-life/effectiveness-wise - shows a decline in activity from start - finish, or some sort of bobbling pattern


Group 3 exists because it allows for double-blinding where this is possible.

 

We could be waiting forever if we wait for "well-designed clinical trials". I've had ME for 32 years now and I'm still waiting.

 

Tried it a long time ago, back when it was all the rage. It’s hard to recall the specifics. Some mild initial improvement in ME symptoms but it was coupled with worsening of sleep disturbance and gastroparesis so I had discontinue it.