A Novel Nutriceutical Treatment of ME/CFS, 2017, Comhaire

I came across a reference to Comhaire on a blog I like (Follow ME in Denmark) which was discussing impaired pyruvate dehydrogenase (PDH) functioning in ME/CFS i.e. Fluge & Mella's 2016 study.

The blog also refers to a study on those born with a genetic impairment of PDH (Patel et al: The spectrum of pyruvate dehydrogenase deficiency) and the study showing elevated lactate in ME/CFS (Natelson et al: Multimodal and simultaneous assessments of brain and spinal fluid abnormalities in chronic fatigue syndrome).

Fluge & Mella proposed that "something/s in the blood" was impairing PDH functioning. So presumably you need to find and turn off the production of that something/s. Ron Davis, as well as Fluge & Mella (and others) are looking for that something/s.

I'm grateful to those who wrote the above posts ie. pointing out the flaws in Comhaire's claims. Presumably until we know more about the causes of ME/CFS there will be suggested cures/treatments which simply do not help.

We need to try to help Ron Davis, Fluge & Mella (and others), possibly by trying to get our Members of the European Parliament/Members of the Westminster Parliament/other parliament to fund this type of biological research. The UNREST film might help.

Thanks again for the cautionary comments re Comhaire's suggested "treatment" and please think about how we might influence those who can fund research.

 

Thank you all for constructive comments. Yes, this is a preliminary trial. Today, more than 20 patients have been enrolled. The initial cases have taken the treatment during 6 months, and continue to benefit. Yes, a placebo-controlled trial should be performed. But, in order to start such a trial it is mandatory to perform a initial trial for dose finding, assessment of possible adverse effects, and estimating the proportion of patients who are expected to respond favourably.

The paper highlights the fact that many patients do not suffer from primary idiopathic ME/CFS, although they were all labeled with this diagnosis by specialised ME/CFS reference centres of the Belgian Universities.
All patients were "refractory" to previous treatments, including CBT and GET, and - commonly - also long-term antibiotic intake or hormone treatment.
The paper highlights the aspect of failed diagnosis, where patients suffered from "ME/CFS nondisease", since they were all given this particular diagnosis based on criteria and complementary tests, but in fact had "secundary" ME/CFS requiring a different treatment.

The paper also sustains the recent hypothesis regarding the metabolic pathogenesis of primary ME/CFS.
The application of the main constituent of the nutriceutical (or nutraceutical) for the treatment of ME/CFS-patients is submitted for patent application. Therefore, temporary discretion must be respected. As soon as the patent has been granted alle details will be revealed.

During their long lasting disease period (average over 8 years) these patients have not noticed any benefit of previous treatments. More than half of the patients in the present trial equally did not respond to the treatment. This suggests that the "placebo" effect may not be of pivotal importance. Moreover, a few patients who had to interrupt the treatment because of a stock brake of the nutriceutical, recorded a recurrence of their poor health situation after no longer than 3 days.

Please read this paper for what it is aimed at, as clearly expressed in the title. It is not more, but also not less than the message in it.

 

Good morning ME/CFS welcome to S4ME, we're delighted to have you join us and discuss this trial.

 

The problem with citing the failure of CBT/GET or other previous treatments to create an ongoing placebo effect, is that the placebo effect wears off eventually. For example, PACE showed mild subjective improvements from CBT/GET months after those therapies ended, but the 2.5 year followup showed that the effect had worn off. Hence I don't think that the general lack of a long-term susceptibility to a placebo effect can be used to demonstrate that patients are not susceptible to such an effect in the shorter term.

Will you be using more appropriate outcome measurements in the future? Fatigue scores are a bit of a bad joke. Many of us would much rather see something objective which is relevant to being physically disabled, and which takes PEM into account. 2-day CPETs would probably be the gold standard, but that's somewhat impractical due to causing further illness. Perhaps actometers could be worn for a week before the trial and again at the end of the trial?

For researching efficacy of a treatment (versus misdiagnosis rates at fatigue clinics) it's also essential to use a diagnostic criteria where PEM is mandatory, such as the ICC, CCC, or IOM criteria. Otherwise it's impossible to know if the research actually applies to ME/CFS, or if it merely applies to a broader range of fatigue where the results of ME patients may be masked by the results of a larger group of non-ME patients.

 

I would go a bit further and perhaps look at at least 8 weeks follow up using both subjective and objective measures for activity and cognitive function (although the latter would be more tricky). Preferably looking at 3, 6 and 12 month reviews.

 

I don't think it will work either (as a cure), but it might provide symptom relief/improvement. At least this is my personal experience.

 

I heard the term years ago when a vet recommended a neutraceutical (for my pet). As I hadn't heard of it at the time I did some reading - I concluded it is a mix of minerals, vitamins, trace elements etc that are mixed together to treat a type of condition (rather than being a general supplement). In my case it was for joint degeneration. So it probably would also cover equivalent human treatments ie glucosamine & condroitin & whatever else.
It may well have been a term created to make it sound like it is more scientific than a "supplement" and therefore they can charge more for it! But it is a well used term in vet speak.

 

Would this be the same vets as are apparently using homeopathy, or different ones

 

https://www.merriam-webster.com/dictionary/nutraceutical

 

thanks, once again, for constructive remarks.

Fatigue is a subjective feeling which is extremely hard to objectivate. Exhaustion, lactic acid accumulation, sleep disturbance etc. can be measured, but the feeling of fatigue can only be estimated by using questionnaires. Patients expressing that they were clearly less tired, and could resume their activity, and in whom the FSS was decreased by at least 15%, were considered responders. If the subjective feeling of fatigue was decreased, but the FSS was not, or vice versa, they were considered non-responders.

Again I insist on the fact that the nutriceutical (food supplement containing vitamins, amino acids, minerals and plant extracts with medical application, in French called ALICAMENTS) are not to be confounded with homeopathy. The effect of several of such nutriceuticals has been proven for the treatment of e.g. male infertility, migraine, metabolic syndrome, hyperlipaemia, and benign prostate hyperplasia. For each of these conditions, specific mixtures of ingredients are being used. I have published the results of trials with these nutriceuticals, both open-label trials and placebo controlled studies. Several of these studies add biological "surrogate markers" to the clinical findings, whenever possible.

I repeat that the prime purpose of treating patients with fatigue is to make them feel better, to increase their "energy" so that they can resume their "normal" professional and familiy life, albeit often with limitations. In general, this is the purpose of medicine.
Now, giving insulin to patients suffering of diabetes does not cure their disease, but improves their health and quality of life. Giving the nutriceutical I have used DOES NOT CURE ME/CFS, but it interferes with (one of) the probable pathogenetic mechanisms, improving the quality of life of a proportion of them. Since the nutriceutical is not toxic and causes no adverse effects, the benefit over risk ratio is positive. Also, the basic ethical rule "first do not harm" (primum non nocere, Hippocrates of Kos, MD, 460-377 BC) is honoured.

Regarding poor studies SUCH as PACE etc. I like to refer to my publication in attachment.

I am a retired professor of internal medicine, endocrinology and metabolic diseases, having published approximately 700 scientific papers, and lectured at 400 congresses and symposia over the world. I have been teaching at Ghent Univesity for 40 years and have personnaly treated several tenthousands of patients. I have organised several multicentre trials in my function of steering committe member of the World Health Organisation. I know the limitations of the present paper, which I clearly mention. So, once again, read the paper for what it contains, and not more nor less.

 

The problem with this is that we don't care about "fatigue". Fatigue isn't what disables us, or makes our lives more unpleasant. When we initially go to a doctor, it usually isn't because we are fatigued. It's because we're disabled, in pain, can't stand up without getting light-headed, or a dozen other symptoms. And if we had a list of symptoms we'd like to go away, fatigue probably wouldn't make the top 20.

There's a reason patients hate the name "chronic fatigue syndrome", and it's because we aren't particularly fatigued. We're sick and disabled. The primary source of our disability is post-exertional malaise, where we get very sick after activity, lasting for days or weeks. PEM involves a variety of symptoms, primarily the exacerbation or onset of neurological, immunological, and muscular symptoms. PEM is what keeps us housebound, bedbound, or unable to live like we used to. Accordingly, it's typically the symptom which we care about the most, and would find most indicative of actual improvement or worsening.

Even if a treatment doesn't help with PEM, it might be helpful if it impacts upon another symptom, especially if it improves our quality of life with regards to sleep, pain, etc. But if your work remains focused on fatigue, it's of little value to us. It's especially problematic if a treatment makes patients feel more energetic with no corresponding increase in activity capacity, as it can push us into over-exerting and crashing and being less functional, all while feeling less "fatigued".

 

It must be possible to measure this objectively, eg., with the actometers others have mentioned. Relying on questionnaires about fatigue is just bad science - they are too easily influenced by whatever bias you want to name.

 

Echoing what Valentijn said above. Fatigue is not the main symptom in ME/CFS. For example, I never feel particularly tired or fatigued, but very, disablingly, ill (flu-like) and that is the case for most of us. I truly rue the day that a panel of doctors in the 1980s decided to invent the laughably inappropriate name 'chronic fatigue syndrome' as a replacement for the more aptly descriptive myalgic encephalomyelitis. As a result, an entirely different condition called 'chronic fatigue' began being mistakenly conflated with 'chronic fatigue syndrome' because of the similarity of names, and then CFS proceeded to get simplified into just 'fatigue' or 'tiredness' (especially thanks to the awful Oxford Criteria), when nothing could be further from the truth. Valentijn's description of the condition is spot-on.

The work you're doing sounds very laudable, but may be more of help to those with chronic fatigue and possibly not so much for chronic fatigue syndrome, especially if fatigue is the only symptom you're measuring. Still could be worthwhile for those who do have a fatigue-based condition.

ETA: Yes, as mentioned in the above post, objective measures such as actometers would be a good idea.

 

I regard a day when my only symptom is "tiredness" or "fatigue" as a good day.