3 ms·

Robert Naviaux is the real deal and his theory on the Cell Danger Response is fascinating [1]. In addition to ASD, he recently made a significant discovery in t

Robert Naviaux is the real deal and his theory on the Cell Danger Response is fascinating [1]. In addition to ASD, he recently made a significant discovery in the characterization of Chronic Fatigue Syndrome as a metabolic illness [2]. [1] http://naviauxlab.ucsd.edu/wp-content/uploads/2016/09/cell_danger_response.pdf http://naviauxlab.ucsd.edu/wp-content/uploads/2016/09/cell_d... [2] http://naviauxlab.ucsd.edu/wp-content/uploads/2016/08/PNAS-2016-Naviaux-1607571113.pdf http://naviauxlab.ucsd.edu/wp-content/uploads/2016/08/PNAS-2...

DiabloD3 9y ago
Wait, how was Chronic Fatigue not a metabolic illness? I always assumed it was a mitochondrial disfunction from the way it was described in the literature.
- lsiebert 9y ago
  Many people believed it to be a psychological disorder.
  - stult 9y ago
    Maybe it's my philosophical materialism, but I've never found that to be a satisfactory alternative explanation for anything. What can explain a psychological disorder other than underlying physical disease? Attributing a disease to psychological disorder is indistinguishable from saying "we don't understand what causes this."
    - naasking 9y ago
      > What can explain a psychological disorder other than underlying physical disease? Attributing a disease to psychological disorder is indistinguishable from saying "we don't understand what causes this." It might be ultimately reducible in this way, but the treatments for various psychological conditions are often very different than physiological problems.
      - didibus 9y ago
        Right, but that's also often just due to limitations in science. All psychological problems are physical, they're just very complex physics and chemistry of the brain which we still don't understand and have no medicated or surgical ways of altering for the better. Just as you can heal a muscle injury with simple rehabilitating exercises, some psychological injuries can be rehabilitated similarly with exercise of the brain. That doesn't change the physicality of it.
    - cpncrunch 9y ago
      >What can explain a psychological disorder other than underlying physical disease? It's well established that the causality works both ways, i.e. physical illnesses can cause psychological symptoms, and psychological factors can cause physical symptoms, e.g.: - fever-causing illnesses cause "sickness behaviour" consisting of depression, anxiety, fatigue, brain fog and other symptoms, causing by pro-inflammatory cytokines. - exam stress has been shown to significantly increase EBV antibodies. - psychological stress causes significant changes to the immune system through the effects of cortisol and adrenaline (the two main stress hormones are also two of the main immune modulators). - psychological stress causes a release of TNF-a (a pro-inflammatory cytokine that is involved in sickness behaviour). - fear causes bowel movements, due to the fact that the HPA axis (the main stress system) also influences bowel motility. >Attributing a disease to psychological disorder is indistinguishable from saying "we don't understand what causes this." Not really. If there are factors that point to psychological causation, it should be considered as much as other possible causes.
- zkms 9y ago
  There was an infamous clinical trial called "PACE" that purported to show that psychotherapy (CBT), along with exercise ("graded exercise therapy", or "GET") gradually increased beyond one's initial limits, was an effective treatment for chronic fatigue. The idea is that CFS patients do not have a metabolic illness; rather, they are suffering from self-reinforcing "unhelpful beliefs" that cause them to fear and avoid physical activity. Even the very act of attributing one's chronic fatigue to a physical illness is itself pathologised (and is to be attenuated via CBT) under this framework. However, the PACE trial was a complete bodge; the protocol and criteria for classifying "recovery" were changed during the trial (to the point that a patient that got worse could nevertheless be classified as having "recovered), the outcome measures were subjective and self-reported (which are liable to be affected by CBT or other forms of social pressure), and conflicts of interest were not reported to participants. Re-analyses of the data were thwarted by the fact that the researchers did not publish anonymised trial data, which violated the requirements of one of their funding sources and the requirements of one of the journals in which they published. There were plenty of methodological criticisms of the trial (http://www.virology.ws/2015/10/21/trial-by-error-i/ http://www.virology.ws/2015/10/21/trial-by-error-i/) but the actual trial data was still not available. Academicians and patients alike unsuccessfully tried to get access to anonymised PACE data for years, and the PACE researchers did their absolute best to prevent that from happening -- including labelling legitimate requests for anonymised trial data (that they were obliged to publish) and criticism of their study as "vexatious" and "harassment" in a BMJ feature article (https://doi.org/10.1136/bmj.d3780 https://doi.org/10.1136/bmj.d3780). The Information Commissioner's Office ordered the PACE researchers to release the trial data, the researchers appealed that decision -- and got laughed out of court. The tribunal concluded that there indeed was a very strong academic interest in the data being released, that it was sufficiently anonymised to prevent re-identification, and went as far as to say that the PACE researchers were overly disparaging of patient groups and skeptical researchers -- and that legitimate requests for trial data and criticism of the PACE study did not constitute harassment. Given how hard the PACE researchers tried to prevent release of the anonymised trial data, the results of the independent re-analysis (http://dx.doi.org/10.1080/21641846.2017.1259724 http://dx.doi.org/10.1080/21641846.2017.1259724) should not be too surprising. There was no basis for an in-flight change to criteria and protocols and CBT/exercise did not provide a statistically significant change in recovery. There are other serious issues with the PACE study's methods that are addressed in http://www.virology.ws/2017/03/13/an-open-letter-to-psychological-medicine-about-recovery-and-the-pace-trial/ http://www.virology.ws/2017/03/13/an-open-letter-to-psycholo... or in the independent reanalysis linked (and there's a quite decent timeline and overview of the PACE trial here: http://me-pedia.org/wiki/PACE_trial http://me-pedia.org/wiki/PACE_trial). Serious biological research (not nonsense by CBT-obsessed wankers who lie with statistics) into CFS continues and there's indeed many findings on potential biomarkers for CFS -- more keeps getting published, 10.1186/s40168-017-0261-y nor 10.1186/s12967-017-1161-4 weren't there last time I looked into this, for example. There's robust evidence of biomedical anomalies in CFS patients -- far more than enough for CFS to be considered a legitimate medical syndrome and not a psychiatric/psychological/"somatic" syndrome. That we haven't yet identified a biomarker useful for diagnosis nor know an aetiology certainly shouldn't disqualify CFS from being a medical syndrome! Since there's plenty of evidence against the PACE trials' findings -- why do CFS patients object to it? After all, papers regularly do get proven wrong or have their findings revised, it's kinda how science operates. It's not the actual publication of the PACE results that have caused harm -- it's how the results were used. Since PACE was the first clinical trial of its scale on CFS patients, its findings ended up single-handedly defining clinical policy, treatment recommendations, and public policy relating to welfare and insurance. CBT and making patients do physical exercise is infinitely cheaper than any sort of medical treatment; and if the PACE trial happened to find that those will help people with CFS "recover" and get back to work, well, that's just a happy coincidence. That CBT is useless and excessive physical exercise harmful to CFS patients is immaterial; there's research that says it helps, so if you're a recalcitrant patient who complains, you're clearly not doing the CBT or the exercise enough! Similarly, the mere belief that CFS has a physical (and not psychological) cause is explicitly called out as one of the "harmful beliefs" that CBT is to neutralise -- disagreement with the treatment method (or familiarity with current medical research) is itself a sign that you're not taking CBT seriously. It is not just through treatment guidelines (and denial of medical access beyond CBT and forced exercise) that the PACE results have materially harmed patients. Extremely unusually for a clinical trial, PACE was funded by the UK DWP -- and could not have returned better results to justify the DWP's agenda of cutting disability spending: http://www.centreforwelfarereform.org/uploads/attachment/492/in-the-expectation-of-recovery.pdf http://www.centreforwelfarereform.org/uploads/attachment/492... . The DWP wanted findings to show that CBT and GET would get disabled people off benefits; and the PACE researchers (by changing the protocol/criteria halfway through) handed that to DWP on a silver platter. That CBT/GET are, in reality, useless (at best) is immaterial here -- DWP doesn't give a flying fuck whether people actually do get better or even manage to survive without disability benefit, they only needed these published findings to justify benefit cuts.
themgt 9y ago
Wow, that abstract is quite simply epic: The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.
- deleted 9y ago
  [deleted]
kineticfocus 9y ago
Research connected to cellular metabolism seems to be gaining momentum, I recall something on high levels of folic acid [1] not too long ago. [1] http://time.com/4327645/folic-acid-autism-pregnancy-b12-folate/ http://time.com/4327645/folic-acid-autism-pregnancy-b12-fola... [2] Effect of High Folic Acid Diet on Mitochondrial DNA Content in Young Adult and Aged Mice - http://www.fasebj.org/content/30/1_Supplement/1171.4 http://www.fasebj.org/content/30/1_Supplement/1171.4

DiabloD3 9y ago

Wait, how was Chronic Fatigue not a metabolic illness? I always assumed it was a mitochondrial disfunction from the way it was described in the literature.

lsiebert 9y ago
Many people believed it to be a psychological disorder.
- stult 9y ago
  Maybe it's my philosophical materialism, but I've never found that to be a satisfactory alternative explanation for anything. What can explain a psychological disorder other than underlying physical disease? Attributing a disease to psychological disorder is indistinguishable from saying "we don't understand what causes this."
  - naasking 9y ago
    > What can explain a psychological disorder other than underlying physical disease? Attributing a disease to psychological disorder is indistinguishable from saying "we don't understand what causes this." It might be ultimately reducible in this way, but the treatments for various psychological conditions are often very different than physiological problems.
    - didibus 9y ago
      Right, but that's also often just due to limitations in science. All psychological problems are physical, they're just very complex physics and chemistry of the brain which we still don't understand and have no medicated or surgical ways of altering for the better. Just as you can heal a muscle injury with simple rehabilitating exercises, some psychological injuries can be rehabilitated similarly with exercise of the brain. That doesn't change the physicality of it.
  - cpncrunch 9y ago
    >What can explain a psychological disorder other than underlying physical disease? It's well established that the causality works both ways, i.e. physical illnesses can cause psychological symptoms, and psychological factors can cause physical symptoms, e.g.: - fever-causing illnesses cause "sickness behaviour" consisting of depression, anxiety, fatigue, brain fog and other symptoms, causing by pro-inflammatory cytokines. - exam stress has been shown to significantly increase EBV antibodies. - psychological stress causes significant changes to the immune system through the effects of cortisol and adrenaline (the two main stress hormones are also two of the main immune modulators). - psychological stress causes a release of TNF-a (a pro-inflammatory cytokine that is involved in sickness behaviour). - fear causes bowel movements, due to the fact that the HPA axis (the main stress system) also influences bowel motility. >Attributing a disease to psychological disorder is indistinguishable from saying "we don't understand what causes this." Not really. If there are factors that point to psychological causation, it should be considered as much as other possible causes.
zkms 9y ago
There was an infamous clinical trial called "PACE" that purported to show that psychotherapy (CBT), along with exercise ("graded exercise therapy", or "GET") gradually increased beyond one's initial limits, was an effective treatment for chronic fatigue. The idea is that CFS patients do not have a metabolic illness; rather, they are suffering from self-reinforcing "unhelpful beliefs" that cause them to fear and avoid physical activity. Even the very act of attributing one's chronic fatigue to a physical illness is itself pathologised (and is to be attenuated via CBT) under this framework. However, the PACE trial was a complete bodge; the protocol and criteria for classifying "recovery" were changed during the trial (to the point that a patient that got worse could nevertheless be classified as having "recovered), the outcome measures were subjective and self-reported (which are liable to be affected by CBT or other forms of social pressure), and conflicts of interest were not reported to participants. Re-analyses of the data were thwarted by the fact that the researchers did not publish anonymised trial data, which violated the requirements of one of their funding sources and the requirements of one of the journals in which they published. There were plenty of methodological criticisms of the trial (http://www.virology.ws/2015/10/21/trial-by-error-i/ http://www.virology.ws/2015/10/21/trial-by-error-i/) but the actual trial data was still not available. Academicians and patients alike unsuccessfully tried to get access to anonymised PACE data for years, and the PACE researchers did their absolute best to prevent that from happening -- including labelling legitimate requests for anonymised trial data (that they were obliged to publish) and criticism of their study as "vexatious" and "harassment" in a BMJ feature article (https://doi.org/10.1136/bmj.d3780 https://doi.org/10.1136/bmj.d3780). The Information Commissioner's Office ordered the PACE researchers to release the trial data, the researchers appealed that decision -- and got laughed out of court. The tribunal concluded that there indeed was a very strong academic interest in the data being released, that it was sufficiently anonymised to prevent re-identification, and went as far as to say that the PACE researchers were overly disparaging of patient groups and skeptical researchers -- and that legitimate requests for trial data and criticism of the PACE study did not constitute harassment. Given how hard the PACE researchers tried to prevent release of the anonymised trial data, the results of the independent re-analysis (http://dx.doi.org/10.1080/21641846.2017.1259724 http://dx.doi.org/10.1080/21641846.2017.1259724) should not be too surprising. There was no basis for an in-flight change to criteria and protocols and CBT/exercise did not provide a statistically significant change in recovery. There are other serious issues with the PACE study's methods that are addressed in http://www.virology.ws/2017/03/13/an-open-letter-to-psychological-medicine-about-recovery-and-the-pace-trial/ http://www.virology.ws/2017/03/13/an-open-letter-to-psycholo... or in the independent reanalysis linked (and there's a quite decent timeline and overview of the PACE trial here: http://me-pedia.org/wiki/PACE_trial http://me-pedia.org/wiki/PACE_trial). Serious biological research (not nonsense by CBT-obsessed wankers who lie with statistics) into CFS continues and there's indeed many findings on potential biomarkers for CFS -- more keeps getting published, 10.1186/s40168-017-0261-y nor 10.1186/s12967-017-1161-4 weren't there last time I looked into this, for example. There's robust evidence of biomedical anomalies in CFS patients -- far more than enough for CFS to be considered a legitimate medical syndrome and not a psychiatric/psychological/"somatic" syndrome. That we haven't yet identified a biomarker useful for diagnosis nor know an aetiology certainly shouldn't disqualify CFS from being a medical syndrome! Since there's plenty of evidence against the PACE trials' findings -- why do CFS patients object to it? After all, papers regularly do get proven wrong or have their findings revised, it's kinda how science operates. It's not the actual publication of the PACE results that have caused harm -- it's how the results were used. Since PACE was the first clinical trial of its scale on CFS patients, its findings ended up single-handedly defining clinical policy, treatment recommendations, and public policy relating to welfare and insurance. CBT and making patients do physical exercise is infinitely cheaper than any sort of medical treatment; and if the PACE trial happened to find that those will help people with CFS "recover" and get back to work, well, that's just a happy coincidence. That CBT is useless and excessive physical exercise harmful to CFS patients is immaterial; there's research that says it helps, so if you're a recalcitrant patient who complains, you're clearly not doing the CBT or the exercise enough! Similarly, the mere belief that CFS has a physical (and not psychological) cause is explicitly called out as one of the "harmful beliefs" that CBT is to neutralise -- disagreement with the treatment method (or familiarity with current medical research) is itself a sign that you're not taking CBT seriously. It is not just through treatment guidelines (and denial of medical access beyond CBT and forced exercise) that the PACE results have materially harmed patients. Extremely unusually for a clinical trial, PACE was funded by the UK DWP -- and could not have returned better results to justify the DWP's agenda of cutting disability spending: http://www.centreforwelfarereform.org/uploads/attachment/492/in-the-expectation-of-recovery.pdf http://www.centreforwelfarereform.org/uploads/attachment/492... . The DWP wanted findings to show that CBT and GET would get disabled people off benefits; and the PACE researchers (by changing the protocol/criteria halfway through) handed that to DWP on a silver platter. That CBT/GET are, in reality, useless (at best) is immaterial here -- DWP doesn't give a flying fuck whether people actually do get better or even manage to survive without disability benefit, they only needed these published findings to justify benefit cuts.

themgt 9y ago

Wow, that abstract is quite simply epic: The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.

deleted 9y ago
[deleted]

kineticfocus 9y ago

Research connected to cellular metabolism seems to be gaining momentum, I recall something on high levels of folic acid [1] not too long ago. [1] http://time.com/4327645/folic-acid-autism-pregnancy-b12-folate/ http://time.com/4327645/folic-acid-autism-pregnancy-b12-fola... [2] Effect of High Folic Acid Diet on Mitochondrial DNA Content in Young Adult and Aged Mice - http://www.fasebj.org/content/30/1_Supplement/1171.4 http://www.fasebj.org/content/30/1_Supplement/1171.4