Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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That is worrying but I think we should wait for the published paper to see what Hanson has measured and what results she got before we declare doom and gloom. If I recall correctly, her sample size was tiny.
OK, I'm VERY non technical about ME stuff but I think even I can appreciate this View attachment 17084
This is where Dr Hanson is comparing some of the results from her metabolic study that she talks about to the recent study by Dr Naviaux (Naviaux on left, Hanson on right). Significant common results found and both studies confirmed a hypometabolic state!!
Skip to 18 mins in if you want to get straight to the metabolic stuff
@Rose49, I’ve been following your Twitter account, and I want to say how sorry I am that you’ve been on the receiving end of abusive posts from a few patients regarding the Naviaux paper.
I’m shocked and appalled by these insulting comments, especially in light of what your daily life is like as a caregiver, and in light of the enormous help you and Dr. Davis have given our community.
I’m truly baffled by these patients’ motivations. I understand that sickness can lead to boredom, irritability and lashing out, but their recent conduct is absolutely inexcusable. Unfortunately, every community has a few bullies.
Please know that these patients do not speak for 99% of us. The vast majority of us recognize that the Naviaux paper is promising and we deeply appreciate the work of Dr. Naviaux, Dr. Davis, Dr. Gordon, and the other researchers working to help us.
I wish people would stop imputing to Drs. Naviaux and Davis ideas that these scientists have never expressed. If people want to critique the paper and subsequent statements on scientific grounds, fine! They should quote the material rather than hurling invective. And when quoting, they should not use ellipses to conveniently remove the part of the quote that undermines their claim. (That’s a common trick of academics and bullies.)
@Rose49, if you wanted to take a break from Twitter, we would understand. We know that you need to protect yourself and Dr. Davis so that you can take care of Whitney.
(@Ben Howell, could you send this to Janet? Thank you!)
We are getting organized and way too strong for the taste of a lot of people. They will try to divide from within. There are too many agendas and interests being threaten.
Do not fall on provocation, do not attack people trying to help us.
Always question if the person is really CFS patient, we all know each other around here.
Be aware of new people.
Of course hidden behind the 96% score may be exactly such a 60/10 split for some major variables and it may pan out as something of key importance. Maybe we need a friendly FOI request for the raw data!
I’m shocked and appalled by these insulting comments, especially in light of what your daily life is like as a caregiver, and in light of the enormous help you and Dr. Davis have given our community.
I'm also fed up with what I've seen on Twitter. I think it's particularly out of order because Rose is acting as a carer and as a go-between, and she's been good enough to do that in spite of the huge demands on her time. I'm very happy with the huge amount of work being done by Ron Davies, Naviaux, and others.
You may be right. But there is something that does not quite fit for me here. If this is a question of a heterogeneous mix of overlapping pathway shifts then it is extremely unlikely that any replicable formula based on MVA will identify 94-96% of cases correctly. As you know you can always produce a formula that will identify a group this precisely within a cohort but if things are very heterogeneous then almost by definition this is going to be a non-replicable formula.
Of course hidden behind the 96% score may be exactly such a 60/10 split for some major variables and it may pan out as something of key importance. Maybe we need a friendly FOI request for the raw data!
More to the point a rapid re-run with another blinded controlled cohort like the UK Biobank could turn this from a maybe into a racing certainty.
I was thinking there may not be an obvious formula (or cluster) but rather a broad region for ME that would be separable from normal and other illnesses. Not necessarily from different pathways but just as the disruption of a system in one direction may not be particularly consistent or predictable.
For any classification system it needs to be tested on unseen data which this clearly has not been. It is that testing that would give the real performance figures as you say not some fit of a model on the data you are fitting.
From what I remember for each dimension you add to a model you are fitting it is a good idea to double the size of your dataset. So I suspect we need vastly more data - both for normal, ME and other illnesses.
It would be interesting to see the data as you say.
My initial thought was if the data is replicated and it suggests certain metabolic systems are functioning strangely does that point us in a direction for say an what an auto-antibody may be doing?
Have we seen any comment on Naviaux's explanations from other mitochondrial experts? Or on him or his work in general, for a point of reference? I mean, he (and his team) seems to be blazing a wonderfully revolutionary trail, with CDR, new techniques and equipment, and in his 2012 'Oxidative Shielding' paper he's explicitly railing against the orthodoxy:
I report evidence that the mainstream field of oxidative damage biology has been running fast in the wrong direction for more than 50 years.
Dr. Matthew O' Connor:
Reading this quickly I'm going to give a snap reply that our mitoSENS project might not help this kind of "homeostasis" problem, if that problem isn't caused by the loss of mito encoded genes. Mitochondrial are indeed complex organelles with much cross-talk with the rest of the cell so our philosophy is always that the underlying problem needs to be addressed. If the problem is in the nuclear genes then that's what needs to be fixed. If the problem is in the lysosome - resulting in reduced mito turnover then we need to fix the lysosome rather than the mitochondria.
Aubrey de Grey:
Exactly. It is often forgotten that mitochondria are constantly recycled even in non-dividing cells, and thus that the only damage they can possibly accumulate other than as a side-effect of something extramitochondrial is DNA damage, and only then if somehow mutant mtDNA is selected for. Historical aside: after Harman first suggested the role of mitochondria in aging in 1972, the only published reaction by anyone prominent was that Alex Comfort in 1976 rejected it on exactly this basis. He did not, of course, consider the bizarre possibility that mutant mtDNA could be selected for, which was only shown in 1993.
As anti-climatic as expected, heh. Although this opened my eyes to how mitochondria are continually being autophagocytosed (by cell lysosomes) and each last only 2-4 weeks at most [1], perhaps as little as 1-2 days (e.g. in mouse liver cells [2]). Any accuracy advances on those time scales? Pretty fast either way.
It's not something one hears or thinks about much in the context of 'mitochondrial damage'. That to be in a state of bad repair they would presumably have had to have been dealt significant damage in the previous few days (to weeks), or else have been 'born' with irreversible mtDNA damage, as seems ubiquitous with regular aging (AKA senescence).
So I think Naviaux's mitochondria switched to a low-power mode, makes good sense, given that, unlike aging, it's sometimes possible to reverse/escape CFS, currently.
Sorry, I don't know what forum threads there are already examining the ins and out of mitochondria(?). Also, I've dived in at the deep end here, for a first forum post, and feeling somewhat intimidated by the ample experience on hand. I've tried to read as much of the thread as possible over previous weeks, but I keep slipping away before getting through enough to make a fully informed reply...
Personally, I was very enthused by the study, follow-up Q&A, reading up on the cell danger response, etc. Naviaux's explanations felt very assured and authoritative. Except for this little bit about methylation related B-vitamins as a therapy, which seemed vague and halting by comparison - second hand insights from CFS clinical experts he's worked with on this?:
Incremental improvements in NADPH production could theoretically be supported by interventions directed at folate, B12, glycine, and serine pools, and B6 metabolism (SI Appendix, Fig. S6), however the safety and efficacy of these manipulations have not yet been tested in a rigorously designed clinical trial.
I feel that his work on how CDR activation at specific ages causes developmental disorders is extra-intriguing in it's potential explanatory power, for my case specifically, since I have ADHD-PI and consider myself on the shallow end of the autism spectrum. Also, that these cognitive idiosyncrasies have merged fairly seamlessly into gradual onset CFS, such that I've only been confident to call it such for the last few years, since age 30 (despite having derailed half my life).
It makes me wonder if I (and maybe other, rarer, 'graduals') have something like a 'more pure' from of CFS... Naturally gravitating to the state, rather than being knocked into it like a metabolic umbrella blown inside-out by infection/trauma (as is more usual). Would this mean that 'recovery' is not then a stable state to be flipped (back) into, with enough well directed efforts? (Or alternatively, if I've just had a stealthy, problematic, latent virus since youth.)
Sick but never sick, fits me too. Refreshing correlation, as frequently fluey often seemed like a core symptom, one I was lacking. Like PEM, which I could never really discern in myself (until recently), having had more like a blanket fatigue; it seemed mostly like reduced brain arousal via cytokine mediated action on the brain stem/hypothalamus - I was able to swing into action for the right type of sport without much comeuppance, just generally lethargic. Since dietary restrictions (which were initially a massive boon) it's like decreased inflammatory (intolerance) signals has increased my ability for low level activity, but exposed a more fundamental cellular metabolic energy limit just beneath, that I was protected from. (Or else I've induced nutritional deficiencies, as I first thought.)
Unexpectedly high DHA is an indicator that fits me, and I'm another one who's perceived a seeming choline difficulty (and fleeting improvement promise via supplementation), so would love to know if reduced sphingolipids (which I'd never heard of before) indeed buttress with that. But unhelpfully anecdotal individual metabolites, sorry...
What's best about recent developments, and Naviaux in particular, is the more integrated systems engineering mentality I'm starting to glimpse....
...Not just big data, but big, deep, understanding of overarching principles. I've found methylation cycle protocols tantalizing, but trying to get through turn-by-turn instructions has been ludicrous in the face of a seemingly Borg like adaptive illness that won't tow the line.
I feel we pwCFS are going to be early beneficiaries of the transition from poking at individual health factors to instead modeling whole complex, dynamic systems, where their characteristic behaviors and interplay are considered, rather than looking for isolated static signposts. I mean, medical science has so far been like trying to describe the minutia of a modern car engine, in plain text, to people who have no intuitive notion of the basic laws of physics, or experience of the 3rd spacial dimension, or time!; one metabolite pushes this one other thing in this direction, sure... But is the serum half-life 5 seconds or 5 months?! And what are the dozen other factors that may affect it several orders of magnitude more, and under what circumstances?!
It's hopeless to model all this in a single human brain (even before accounting for (epi)genetic personalisation). So I'm wondering what the state of bioinformatics is, regarding detailed modeling...? My expectation is that computer modeling (plus expert systems, deep learning, whatever) will fairly soon take big data metabolite measurements from yes/no diagnostics, and painstakingly personalized expert advice, to the point of providing precise, potent, dynamic, intervention recommendations that would often be utterly unexpected and unintuitive to any clinician. Not just for CFS, but for pretty much everything; for continuous health optimization. I wanna see those "novel mass spectrometry-based method"s [3] shrunken down to an implantable chip that give real time readout! Or, well, at least a fairly convenient blood glucose finger prick monitor linked up to a phone app.
@Rose49, I’ve been following your Twitter account, and I want to say how sorry I am that you’ve been on the receiving end of abusive posts from a few patients regarding the Naviaux paper.
I’m shocked and appalled by these insulting comments, especially in light of what your daily life is like as a caregiver, and in light of the enormous help you and Dr. Davis have given our community.
I’m truly baffled by these patients’ motivations. I understand that sickness can lead to boredom, irritability and lashing out, but their recent conduct is absolutely inexcusable. Unfortunately, every community has a few bullies.
Please know that these patients do not speak for 99% of us. The vast majority of us recognize that the Naviaux paper is promising and we deeply appreciate the work of Dr. Naviaux, Dr. Davis, Dr. Gordon, and the other researchers working to help us.
I wish people would stop imputing to Drs. Naviaux and Davis ideas that these scientists have never expressed. If people want to critique the paper and subsequent statements on scientific grounds, fine! They should quote the material rather than hurling invective. And when quoting, they should not use ellipses to conveniently remove the part of the quote that undermines their claim. (That’s a common trick of academics and bullies.)
@Rose49, if you wanted to take a break from Twitter, we would understand. We know that you need to protect yourself and Dr. Davis so that you can take care of Whitney.
(@Ben Howell, could you send this to Janet? Thank you!)
Thank you for posting this! It's easy to be a dismissive "armchair expert" from home, out of touch with the extremely hard day-to-day work and deep thinking that have gone into the Davis/Naviaux research. Plus, the Davis's motivations are clearly totally aligned with those of the patient community since they have a severely ill son. I'm grateful to them and to the other people that support their valuable work, which cannot continue without financial support. I'm sure they will try to put together all the missing pieces of the puzzle, as fast as they can. Sending love and hope to @Rose49.
Hi, I occasionally check out the Follow ME in Denmark website. The most recent blog considers the Naviaux paper and also some recent research into type 2 diabetes (among other research). The diabetes research links gut bacteria to insulin resistance and altered serum (blood) metabolmics. I think I noticed earlier in this blog that someone referred to the Hornig/Lipkin research on gut bacteria and metabolmics; and highlighted that the Hornig/Lipkin research may validate the metabolmics findings in Naviaux's paper. It will be interesting to see if Hornig/Lipkin microbiome study identifies gut bacteria which are responsible for the altered metabolmics in MECFS. It's late and I hope this makes some sense.
Unless we are talking disease, where fat metabolism is slowed?
One example is if the ME CFS sufferer has developed adult Growth Hormone deficiency, which requires a special test practically no patient has had (GH Stimulation test) on here, as most doctors mislead the patient and tell them if their IGF-1 is normal, they can't have adult GH deficiency.
Post diagnosis, If you take injections of GH, the fat falls off your boobs (both sexes) hips and tummy and you feel less anxious, have a stronger heart, less anxiety, basically it makes you way better than trying to exist with a blow pituitary gland.
And it's funny in a way, that a major sign of the 2nd paragraph huge benefits, are being 'skinny fat', or looking like a rotund apple shape which of course we would all miss and put down to genetics or poor diet, as we as patients, tend to believe all the things we have wrong with us is 'ME CFS'.
There was a study done years ago by a woman called greta moorkins I think it was. I remember Nancy klimas saying that if she has used better endpoint/outcome measures that the study would have shown benefit from growth hormone
There was a study done years ago by a woman called greta moorkins I think it was. I remember Nancy klimas saying that if she has used better endpoint/outcome measures that the study would have shown benefit from growth hormone
The efficacy of growth hormone (GH) therapy was evaluated in patients with chronic fatigue syndrome (CFS) who had peak serum GH levels below 10 microg/l during stage-controlled sleep. Twenty patients (7 men, 13 women; age range, 30-60 years) with CFS were randomized to receive placebo or GH therapy, 6.7 microg/kg/day (0.02 IU/kg/day), for 12 weeks. Following this double-blind treatment period, the 17 patients remaining in the study were given GH therapy at the above dose for an open period of 9 months. Mean (+/- SD) serum levels of insulin-like growth factor I (IGF-I) increased during GH treatment, from 173 +/- 46 microg/I to 296 +/- 89 microg/l (P < 0.001); IGF-I SDS values increased from -0.45 +/- 1.14 to +1.43 +/- 1.09 (P < 0.001). Fat-free mass and total body water were significantly increased after 12 months of treatment. Although quality of life, as assessed using two different questionnaires, did not improve significantly during GH treatment, four patients were able to resume work after a long period of sick leave.
I have posted about it on here before. There was no real progress unfortunately as it was too expensive to continue for more than a month.
Although hard to say from such a small trial it probably isnt a cure. In my case anyway. Although I have heard some say their cfs turned out to be low hgh.
I was on the minimum dose and was told I wouldnt feel anything for a few months. I felt a good improvement from the first or second day so may be due to its antinflammatory effects.
The other thing is im told my hgh levels are fine. But then I dont think I have had the correvt test to properly judge that. The other thing is the levels may be normal but the receptors are not utilizing it properly.
Id like to try again but its hard to source and very expensive. I think it was dr Cheney who used to say it was one of his most effective treatments
Regarding use of growth hormone. I'm not going to add much to the sum total of knowledge here but the Naviaux study should help in assessing potential treatments. Also, I'd be surprised if the folks at the Open Medicine Foundation (Ron Davis, Naviaux ---) were unaware of the research you refer to re use of growth hormone. Why not drop the folks at the Open Medicine Foundation an email and ask if they are aware of this/this warrants further investigation?
Also, while you've missed the formal period for submitting suggestion to Vicky Whittemore, you should check the responses received (I was notified that the responses were posted online some time ago) to see if anyone else highlighted this research; if they didn't then consider sending an email to Vicky Whittemore re this research.
It may be difficult to measure the level of this hormone directly in blood (i.e. an easily available sample type) but try online (sorry if I have not read/understood above emails). I keep saying this, here in Northern Ireland Government laboratories get £200 ($270) to measure various things in food (including hormones) using mass spectrometry i.e. technique used in Naviaux study (your Government has a similar program re food safety monitoring). These laboratories also use (from distant memory -- and therefore not up to date) various immune assays to measure hormones.
Diagnosing a problem re receptor for growth hormone is interesting; how do they do that? E.g. in diabetes I think they give you glucose and see how long it takes for your blood glucose levels to return to normal. Presumably if you have normal levels of insulin in your blood (chemical messenger) and you give glucose then if the blood glucose levels do not return to normal in the normal time then the insulin receptor is faulty. To check out your growth hormone you'd need to give -- and check the level of ---.
All been done before I'm guessing so look online.
The scientific challenge of assessing how effective growth hormone is, is one thing; getting your Government to put the systems in place is a whole different challenge!
