Professor Ron Davis's response to Naviaux study, including Q and A with Dr Naviaux

[Ben H]

@Ben Howell, @Rose49

I'm not sure if this question has already been asked, but does Dr. Naviaux or Dr. Davis have an opinion concerning how, if at all, this newly discovered hypometabolic response might be related to the shifting ME/CFS cytokine profile found by Drs. Hornig and Lipkin?

Noting it down @Forbin

Thanks,

B

 

[paolo]

I asked Bob Naviaux to respond to this. Here is his response. I hope it clears things up!
Hi Ron and Janet,
Janet told me about your keen commentary on our paper and told me about what people were calling a “disagreement” between us. I don’t see any disagreement. I’ve added the point to our Q&A. Please let me know if this “agreement” is too controversial for the CFS community at the present time.
Q7. How would you respond to Dr. Ronald Davis’s recent statement: “"What is important to note is that in the absence of evidence of an active infection, it is plausible that the long-term antimicrobial treatments often used for ME/CFS patients are doing more harm than good."

I am in complete agreement.Many antibiotics like tetracyclines, erythromycin, and the fluoroquinolones (eg, Cipro), and antivirals like acyclovir, fialuridine, AZT, and ddC also inhibit mitochondrial functions when used chronically (usually for more than about 3 weeks).Because mitochondria are descendants of free-living bacteria, their machinery for protein synthesis and DNA replication are susceptible to many antibiotics, and for reasons unique to mitochondrial DNA synthesis, they are also sensitive to antivirals.Chronic use of these drugs can do more harm than good if there is no longer good evidence for an active infection.When mitochondrial functions are critically impacted by long-term use of certain antibiotics, a ripple effect in metabolism and gene expression is produced that can further impair energy production by mitochondria, converting an active cell danger response that occurs during active infection to a hypometabolic survival response.

In the field of mitochondrial medicine we are particularly sensitive to these issues of iatrogenic toxicity because some of the drugs that inhibit mitochondrial functions are very commonly used in patients without mitochondrial disease.For example, statins, valproate, and metformin can each produce problems in patients with pre-existing mitochondrial dysfunction.


Bob

Robert K. Naviaux, MD, PhD
Professor of Genetics
Biochemical Genetics and Metabolism
Departments of Medicine, Pediatrics, and Pathology
Co-director, The Mitochondrial and Metabolic Disease Center (MMDC)
UCSD School of Medicine

Thanks Janet @Rose49 for your efforts in this field. This new study is having a big resonance here in Italy. And many of us are interested in performing the metabolic profile. Is it possible to send blood samples from Italy?

As for the above comment by prof Naviaux about the use of antimicrobials in CFS, it still doesn't answer the question about the role of persistent intracellular infections in this disease. In his paper he states that "low sphingolipid profile in CFS ... may represent a fundamental response to oppose the spread of persistent viral and intracellular bacterial infections".

I am particoularly interested in this point as after more than a decade of CFS-like illness (I fulfill IOM criteria, with OI and PEM), I discovered an ongoing infection by Borrelia burgdorferi (PCR+). Treatments for this condition led to the resolution of a form of hypoesthesia (with a pattern suggestive of B. afzelii infection) and to improvements in some of my cognitive issues. Nevertheless, the core CFS symptoms remain, and I am still house-bound with poor cognitive function. I don't like the idea of long-term antibiotics, as I can't find reliable evidence for their efficacy in 'chronic Lyme'. But the concept that this spirochete may be still there is plausible at least in some cases, according to some studies on animal models of infection, which demonstate the survival of spirochetes after even aggressive treatments (Embers, 2012), (Yrjänäinen, 2010).

I think that this study may be relevant in those cases of Lyme disease which fulfill CFS criteria. In fact, those patients who develop a CFS-like illness after the exposure to B. burgdorferi will not manifest macroscopic damages from this infection (heart damages, permanent paralysis, brain lesions); and at the same time, those who are left with lesions to tissues, don't have CFS. I am not able to give a particular reference for this observation, but I have noted this pattern since I entered the Lyme comunity, two yeras ago. And I have always wondered the reason for this different response to the same infection. Now I belive that the answer is in the down regulation of sphingolipids in lipid rafts: those who eneter the hypometabolic state are less vulnerable to intracellular spreading by B. burgdorferi and thus they will not develop permanet tissues damages. The price to pay for preserving their organs, is the sospension of their physical and intellectual life. On the other hand, those who don't use this defensive metabolic response, will not enter the CFS nightmare, but will lose some of their organ integrity, as a consequence of apoptosis.

As Naviaux himself has noted in his paper (supporting information, page 3) B. burgdorferi is one of those bacterial infections (along with Coxiella burnetii) whose intarcellular spreading might be inibithed by the down regulation of sphingolipd-rich and cholesterol-rich lipid rafts. This support the above expressed hypothesis of two disitinc patterns in the immune response to B. burgdorferi.

 

[Gingergrrl]

Laurel's will not be at OMI. It will be through the CFSResarch Center at Stanford, which Ron runs. More details from Laurel soon.

Thanks for clarifying this and I did not understand that part but now do!

That's good to hear you didn't have a head injury. No worries, I am so far behind in reading threads/posts; been focused on Naviaux & Davis.

Thanks and I am really far behind on responding to PM's, e-mails, texts and just about everything. I have gotten totally swept away by this study as well and trying to keep up with the related threads.

 

[Ben H]

I have answered the Montoya part of this q in another thread. Ben, could you find it? Thank you!

I believe this is it @Rose49 :

The CFS Research Center at Stanford (Ron Davis) and the Stanford CFS Initiative (Jose Montoya) are completely separate, independent organizations. Dr. Montoya is a physician that sees patients, and he elicits collaborations with physician/scientists and with research scientists at Stanford so those scientists can investigate various aspects of CFS, and Dr. Montoya provides the patient samples. Ron Davis's training is in biochemistry and genetics, he is a research scientist, not a doctor, and he is investigating the biochemical basis of ME/CFS and the genetic contributions to this disease. He has extensive experience in developing technologies and is developing new technologies for finding a diagnostic test, treatment, and cure for CFS. Dr. Davis has worked with Dr. Montoya using Davis's new technology to sequence the HLA region of patients' DNA from several hundred of Montoya's patients. He has also helped Dr. Montoya with statistical analysis of results on several projects. The CFS Research Center is where Davis does his science, but he plans and coordinates the grand End ME/CFS Project as Director of the Scientific Advisory Board of the OMF.

@msf


B

 

[Never Give Up]

has he tried acupuncture?

Yes. Didn't do a thing.

 

[Starfive]

I also had a retinal hole some 7 years ago @Starfive which though a different condition, involves the vitreous inside the eye pulling on the retina. Some people get detached retinas due to the shape of their eye ball apparently - they are short sighted, but this is not so for me.

Apparently there are a couple of other conditions that have higher incidence of retinal detachment and one of them is Ehlers Danlos Syndrome, and there are quite a few people with ME who also have EDS. I don't think I do have this but I do have hypermobility (severe hypermobility is one of the key features of EDS).

Another vulnerability for retinal detachment is Lattice Degeneration which is a kind of fraying on the edges of the retina and about 10% of the population have that (including me apparently!). It's not usually an issue unless you are going through Posterior Vitreous Detachment which is a kind of normal process that happens in middle age. I think the 2 conditions probably caused my detachment.

thanks for your reply... I have related it to the dryness, major dry eyes and mouth which I experience 24/7... Hope the other eye stays free of fraying!

 

[Sidereal]

The price to pay for preserving their organs, is the sospension of their physical and intellectual life. On the other hand, those who don't use this defensive metabolic response, will not enter the CFS nightmare, but will lose some of their organ integrity, as a consequence of apoptosis.

This is probably the best description of ME/CFS I've ever seen.

 

[Ben H]

Updated initial post with Dr Naviaux's response (Q 7). Will continue to do so (so you guys can just go to the first post and see all answered questions if you lose track in this thread).


B

 

[msf]

I asked Bob Naviaux to respond to this. Here is his response. I hope it clears things up!
Hi Ron and Janet,
Janet told me about your keen commentary on our paper and told me about what people were calling a “disagreement” between us. I don’t see any disagreement. I’ve added the point to our Q&A. Please let me know if this “agreement” is too controversial for the CFS community at the present time.
Q7. How would you respond to Dr. Ronald Davis’s recent statement: “"What is important to note is that in the absence of evidence of an active infection, it is plausible that the long-term antimicrobial treatments often used for ME/CFS patients are doing more harm than good."

I am in complete agreement.Many antibiotics like tetracyclines, erythromycin, and the fluoroquinolones (eg, Cipro), and antivirals like acyclovir, fialuridine, AZT, and ddC also inhibit mitochondrial functions when used chronically (usually for more than about 3 weeks).Because mitochondria are descendants of free-living bacteria, their machinery for protein synthesis and DNA replication are susceptible to many antibiotics, and for reasons unique to mitochondrial DNA synthesis, they are also sensitive to antivirals.Chronic use of these drugs can do more harm than good if there is no longer good evidence for an active infection.When mitochondrial functions are critically impacted by long-term use of certain antibiotics, a ripple effect in metabolism and gene expression is produced that can further impair energy production by mitochondria, converting an active cell danger response that occurs during active infection to a hypometabolic survival response.

In the field of mitochondrial medicine we are particularly sensitive to these issues of iatrogenic toxicity because some of the drugs that inhibit mitochondrial functions are very commonly used in patients without mitochondrial disease.For example, statins, valproate, and metformin can each produce problems in patients with pre-existing mitochondrial dysfunction.


Bob

Robert K. Naviaux, MD, PhD
Professor of Genetics
Biochemical Genetics and Metabolism
Departments of Medicine, Pediatrics, and Pathology
Co-director, The Mitochondrial and Metabolic Disease Center (MMDC)
UCSD School of Medicine

That´s very interesting, thanks Rose49 for asking him.

So, if I have understood his answer correctly, the results of the study do not make the persistent infection hypothesis less likely, but they do change the risk/reward ratio with regards to antibiotic therapy. Or perhaps he only answered the question that was put to him. It´s hard working out what other people think! I really appreciate both Rose49´s and Ben Howell´s efforts in this area though.

 

[mermaid]

thanks for your reply... I have related it to the dryness, major dry eyes and mouth which I experience 24/7... Hope the other eye stays free of fraying!

Well I have not heard of retinal detachment in relation to what you mention, but I am no expert. What do your opthalmologists put it down to? I always like to know reasons but they don't always tell you do they? What kind of age are you?Have you explored Sjogren's syndrome re the dry eyes/mouth issue?

Unfortunately it seems that the fraying issue is in both my eyes (may have contributed to both events I now think as I had retinal tears in both).

 

[snowathlete]

I don't have a pet theory. I pointed out that the researcher isn't even aware of the current state of the art in terms of persistent infection in lyme--which was written up in Scientific American, as I linked to, so isn't hard to find. That 20% have persistent symptoms, ie ongoing infection. Johns Hopkins' research on persisters is pretty widely known, too. I have no pet theory, as I said, but if he's going to say that only a small percentage of people who get lyme go on to chronic symptoms, he's wrong. He ought to know better before he makes statements like that. Moreover, as I said, EBV is not equivalent to nor should it be classed with lyme. It's a universal infection that most of us handle--that is, except for later-in-life cancers, such as b-cell related cancers (where EBV resides)

Where do you get off telling renowned scientists that they ought to know better? According to you, who makes offensive and unfounded accusations against researchers who are working hard to figure the disease out when they could go and get paid loads more easily by taking their skills and reputations and looking into a more trendy disease where funding comes easy. It's really stupid to bite the hand that feeds you, which makes me wonder what your motive is here.

To answer your point above, they don't say that it is "a small percent of people who are acutely infected with Lyme disease go on to develop chronic symptoms. The sentence includes EBV and HHV6. Taking the three together, they are absolutely right, it is a small percent. It it not 1 in 5 who develop chronic symptoms from EBV, HHV6 or Lyme. 1 in 5 is also small compared to 4 in 5, so they wouldn't be wrong even by your misconstrued version, but that isn't what they said so it is irrelevant.

Why do they mention EBV, HHV6 and Lyme? Well, I suspect because they are common infections that cause similar symptoms to ME and which have each been linked with causing ME, or ME-like disease. I don't think it is meant as an exhaustive list, but rather than attacking them, you could ask them why they picked these three, in a respectful way.

Pretty much everyone here thinks this research is top quality, if you don't like it, that's fine, but either engage respectfully or go and do something else. The last thing I want to see is you create a situation where these researchers decide not to engage with us because of a lack of basis courtesy. They don't have to do this research for us, and they certainly don't have to answer our questions and let us feedback into their work by engaging with us. They are doing that for our benefit, but you seem to be trying to ruin that.

 

[msf]

I think people should be reminded to be courteous, especially with those researchers who are actually trying to engage with the ME community. It would be pretty ironic though if a couple of accusations put off someone like Davis, whilst Wessely happily carries on knowing that almost everyone with ME despises him.

 

[ClarkEllis]

Having interviewed Ron Davis for an article on Phoenix Rising, I can say without a shadow of a doubt that Ron is by far the most brilliant scientist I have spoken with. He is probably the smartest and most knowledgeable person I've ever spoken with in any area of life actually. And he was very generous with his time. He is a very nice person, and incredibly humble. He has one motive, which is to do good science, find how this disease works and cure it. He is not interested in credit, or anything like that; he doesn't need it because he already has buckets of it from his previous work. I can't understand the sense in attacking him, and it saddens me.

 

[Ben H]

Where do you get off telling renowned scientists that they ought to know better? According to you, who makes offensive and unfounded accusations against researchers who are working hard to figure the disease out when they could go and get paid loads more easily by taking their skills and reputations and looking into a more trendy disease where funding comes easy. It's really stupid to bite the hand that feeds you, which makes me wonder what your motive is here.

To answer your point above, they don't say that it is "a small percent of people who are acutely infected with Lyme disease go on to develop chronic symptoms. The sentence includes EBV and HHV6. Taking the three together, they are absolutely right, it is a small percent. It it not 1 in 5 who develop chronic symptoms from EBV, HHV6 or Lyme. 1 in 5 is also small compared to 4 in 5, so they wouldn't be wrong even by your misconstrued version, but that isn't what they said so it is irrelevant.

Why do they mention EBV, HHV6 and Lyme? Well, I suspect because they are common infections that cause similar symptoms to ME and which have each been linked with causing ME, or ME-like disease. I don't think it is meant as an exhaustive list, but rather than attacking them, you could ask them why they picked these three, in a respectful way.

Pretty much everyone here thinks this research is top quality, if you don't like it, that's fine, but either engage respectfully or go and do something else. The last thing I want to see is you create a situation where these researchers decide not to engage with us because of a lack of basis courtesy. They don't have to do this research for us, and they certainly don't have to answer our questions and let us feedback into their work by engaging with us. They are doing that for our benefit, but you seem to be trying to ruin that.

I think people should be reminded to be courteous, especially with those researchers who are actually trying to engage with the ME community. It would be pretty ironic though if a couple of accusations put off someone like Davis, whilst Wessely happily carries on knowing that almost everyone with ME despises him.

Basic courtesy is absolutely paramount.

Janet @Rose49 has said and addressed this but to reiterate-if you are going to engage in discussion with Prof. Davis, or Dr Naviaux, courtesy is a basic necessity.

We are unbelievably lucky with this research, and with the researchers onboard. They absolutely do NOT have to answer questions but they do so to help us all.

Comments like ' The researcher isnt even aware in terms of the current state of the art in terms of persistent infection in lyme' is not only wrong, it is an incorrect assumption over a completely reasonable comment. The same goes for the 'follow the money' comment-absolutely false. Prof. Davis is only funded by donations at the moment. This disease is hardly a path to richness.

We are grateful to have people engaging in this-its exactly what we want. And you don't have to agree. But if you do not, state your reasons respectfully.

Lets keep it positive

Thanks,


B

 

[msf]

I think there is a difference between questioning someone´s knowledge and someone´s ethics, too. There will be things about ME that Davis, or any researcher for that matter, doesn´t know, but it is better to question whether they know something rather than just assuming that they don´t. Questioning their ethics (except in clear cases like White and his links to insurance companies) is going too far though.

 

[Hutan]

I think that this study may be relevant in those cases of Lyme disease which fulfill CFS criteria. In fact, those patients which develop a CFS-like illness after the exposure to B. burgdorferi will not manifest macroscopic damages from this infection (heart damages, permanent paralysis, brain lesions); and at the same time, those who are left with lesions to tissues, don't have CFS. I am not able to give a particular reference for this observation, but I have noted this pattern since I entered the Lyme comunity, two yeras ago. And I have always wondered the reason for this different response to the same infection. Now I belive that the answer is in the down regulation of sphingolipids in lipid rafts: those who eneter the hypometabolic state are less vulnerable to intracellular spreding by B. burgdorferi and thus they will not develop permanet tissues damages. The price to pay for preserving their organs, is the sospension of their physical and intellectual life. On the other hand, those who don't use this defensive metabolic response, will not enter the CFS nightmare, but will lose some of their organ integrity, as a consequence of apoptosis.

That was really well put.

I am reminded that a couple of people on PR have reported that MRIs done very early on in their ME illness (at the stage when most of us were still just wondering what an earth had hit us and trying to convince our GPs and ourselves that we weren't imagining things) showed brain lesions. But that MRIs done later showed that the lesions had healed. This would be consistent with the idea of the hypometabolic state being protective.

I wonder if the fact that so many of the Ebola survivors now have ME-like symptoms means that their bodies too adopted this defensive metabolic response to limit damage by the virus.

 

[Mrs Sowester]

Careful people! You run the risk of bringing that poster back for a rematch!
@Rose49 dealt with that situation beautifully - with compassion and class. Our community is behind her and Ron, I'm certain they feel that.
Let's remember that people can behave badly when they are frightened and project their own motivations onto others; kindness and reassurance can be all that is needed to diffuse these situations and that is what Ron and Rose have offered. Very good people, big brains, big hearts!

 

[BurnA]

This is science not religion based on Belief. It is science that will cure them.

Class !

 

[alex3619]

Thanks and I am really far behind on responding to PM's, e-mails, texts and just about everything. I have gotten totally swept away by this study as well and trying to keep up with the related threads.

Its easy to see that happening. I hope you continue to cope.

 

[justy]

Yes, this has been my pattern too. EBV in early 20s, which left me mod-severe for 3.5 years before partial remission (around 65 on Bell scale) for about 15 years, then relapse (severe) 2.5 years ago in my early 40s. I wonder whether my remission (which was never full. I worked, but not full time, was exercise intolerant, and needed lots of downtime) was like a ticking time bomb... something that was inevitably going to blow up. It would be terrific for researchers to compare relapsing/remitting types to those who have not had any sort of remission.

yes! I REALLY want to know how the results of this study could tie in with those of us who have had long remissions or occasional short ones. Last year I had two great months after 8 weeks of myers cocktials with glutathione (3 x a week) - as usual the remission doesn't hold.