I want you all to see an article I just found via Relative Risk Blog. Its about ‘Chronic Lyme Disease’. About a young woman who was aggressively treated by a ‘questionable’ practitioner who had ‘cured herself’ of ‘Chronic Lyme’. No one believes in ‘Chronic Lyme’. ‘Everyone’ was ‘against’ this practitioner, while she insisted she ‘KNEW’ what she was talking about. Questionable tests. Off-label prescriptions. And this practitioner almost killed this young woman.

Janet Love and Dana Rosdahl come across as sincere in their belief that doctors routinely misdiagnose the disease, leading to unnecessary pain and bad health for literally millions of people.

“We know how Lyme works, and we know how to fight it,” Dana Rosdahl says. “But it’s not an easy road for the patients or for us.”

“I believe that at least 70 percent of the population are infected [with Lyme], whether they know it or not,” Love says. “I didn’t, in my own case, for 15 years. We are passing infected blood directly into the blood supply. Some people think this is wacko, but it’s not.”

Alyssa never did test positive for Lyme disease, despite extensive blood work and other evaluations.

But that didn’t stop the clinic from continuing to treat the ailing young woman for full-blown Lyme.

That included a regimen of potent antibiotics that landed Alyssa in a Gilbert emergency room in February 2010.

The most common blood test for Lyme, called the ELISA, provides so many false-positive readings that most doctors won’t use its results as a sole basis for diagnosis.

Prescribing long-term antibiotics to treat what supposedly is “chronic Lyme disease” (in itself a controversial diagnosis) is a practice most doctors see as perilous.

But Rosdahl and Love say what went awry was not their fault.

“Alyssa is a sweet little girl,” Love says, “though I didn’t think she would have the discipline for our program. But Dana decided to treat her out of compassion. We never hurt her.”

She [Love] keeps the desktop devices in her Remnant office and says they accomplish amazing things, including having saved her own life from a vicious bout with Lyme disease.

Insurers also are loath to cover more than a few weeks of antibiotics at a stretch, so Remnant’s long-term patients (which are most of them) have to pay for everything out of pocket.

But business has been good at Remnant since it opened in early 2010.

“I feel better than I have in 30 years since I hooked up with Dr. Dana and Jana and realized what was up,” says Clovis Jones, a 65-year-old Vietnam War veteran and retired airline pilot. “They have saved my life. They know what they are doing, and they know Lyme disease.”

Some Lyme-ites cling to wispy theories of a lingering U.S. government/big-insurance-company conspiracy against the masses.

They consider Lyme as an evildoer of monumental magnitude, and that the “medical establishment,” which includes the insurance industry and the U.S. government, intentionally has misled the American public as to its prevalence.

“If we could support them, they would have been here a long time ago. But people are desperate to figure out what’s making them sick, and they grab onto a Lyme diagnosis whether it’s right or not.”

Some Lyme-ites, including those at Remnant, suggest that the disease also can be transmitted in utero or by sexual contact.

Janet Love is adamant that she contracted Lyme disease genetically from her parents, natives of Missouri and Texas. She also says she’s sure that she transmitted it to her son Garrett (who is Remnant’s office manager).

Alyssa Goodale’s mother, Lynn, says both Love and Dana Rosdahl informed her that all six Goodale children contracted Lyme genetically.

“When Dana first told me that Lyme was passed along in families, it rocked my world, to say the least,” Lynn Goodale says.

Dr. Horwitz adds, “To take a disease and to extrapolate and say that everyone is infected — that based on alleged clinical symptoms, this is Lyme, even in the absence of data — makes no sense to me.”

He adds a cautionary note relevant to Alyssa Goodale’s case:

“In the absence of a clear diagnosis, you shouldn’t just assign something based on your own theories or probabilities and promulgate a myth. That’s when you take a step that’s beyond what we do.”

A recent paper by the American Lyme Disease Foundation concluded, “There is no epidemiological or clinical data to support the sexual transmission of Lyme disease.”

The CDC goes further, saying there is “no evidence that Lyme disease is transmitted from person to person.”

I definitely think Chronic Lyme Disease and Chronic Fatigue Syndrome have something in common, but its not XMRV.

Comments

  1. #1 AZSkeptic
    May 10, 2011

    Yep, that’s here in the Phoenix, AZ area…

    One of the therapists quacks in the story (Janet Love) advertises her qualifications thus:

    She is a board-certified Biofeedback Therapist… as well as a Licensed Quantum Biofeedback Therapist, a Reiki Master, DNA Reprogramming Therapist, Life Coach, and is proficient in Emotional Freedom Technique.

    What could go wrong?

  2. #2 JohnV
    May 10, 2011

    “Alyssa Goodale’s mother, Lynn, says both Love and Dana Rosdahl informed her that all six Goodale children contracted Lyme genetically.”

    What does that even mean? :p

  3. #3 Jon H
    May 10, 2011

    “What does that even mean?”

    It means instead of one patient, now there’s seven! KA-CHING!

  4. #4 ERV
    May 10, 2011

    “What does that even mean?”
    I think its an example of homologous recombinaltion tiniker.

  5. #5 Prometheus
    May 10, 2011

    Hey, we use Quantum Biofeedback at my office. We send out interns to bring us back lunch….a significant “quanta” of lunch.

  6. #6 Bone Oboe
    May 10, 2011

    Reads comment #2; light bulb appears over head.

    Reads comment #4; filament in light bulb breaks and joke is extinguished.

  7. #7 Jesse
    May 10, 2011

    I was diagnosed with Syringomyelia a couple of years ago after a spinal MRI. The condition is very underdiagnosed, and I expect that at least some cases of “chronic lyme disease” can be explained by it. The symptoms are identical.

  8. #8 JohnV
    May 10, 2011

    Good answers :P

  9. #9 stogoe
    May 10, 2011

    Reads comment #6; wonders how many individuals of acceptable target group Y are required to change said light bulb.

  10. #10 Mu
    May 10, 2011

    I find it ironic that the patient in question was saved by her naturopath – woo fight.

  11. #11 John
    May 10, 2011

    The issue isn’t just about whether or not the spirochete persists in ‘Chronic Lyme’, which is what the subject of ‘chronic Lyme’ is often reduced to, but rather what exactly is the nature of post-infectious fatigue syndrome(s)?

    There are numerous infections that have been shown to be followed by a ‘post-infectious’ or ‘chronic’ fatigue syndrome (even though whether they are all truly ‘post-infectious’ is still very much open to question), ranging from EBV/infectious mononucleosis, Coxellia Burnetti/Q-fever, Ross-River virus, SARS, West Nile virus, acute Lyme disease, Giardia lamblia, etc.

    The questions raised by these PIFS’s are many- are all PIFS’s one and the same ‘syndrome’ or is each illness/disease followed by it’s own distinct PIFS? PIFS patients are commonly included in CFS studies, would this make PIFS a subset of CFS, a potential model for CFS or is PIFS a confounding factor in CFS research? How widespread is the issue of PIFS truly? Unexplained fatigue is one of, if not the single most, common causes of visits to physicians and undoubtedly consumes vast quantities of resources, why then is research funding for CFS/PIFS among the lowest of all federally funded research categories?

    When you look just a little further at the issue there are many more relevant questions besides ‘how can I make fun of CFS patients in the most wink-wink nudge-nudge way possible’?

    Refs-

    Chronic Widespread Musculoskeletal Pain, Fatigue, Depression and Disordered Sleep in Chronic Post-SARS Syndrome; a case-controlled study
    http://www.biomedcentral.com/1471-2377/11/37/abstract

    High rate of fatigue and abdominal symptoms 2 years after an outbreak of giardiasis
    http://www.ncbi.nlm.nih.gov/pubmed/19185898

    The Long-Term Outcomes of Human West Nile Virus Infection
    http://cid.oxfordjournals.org/content/44/12/1617.abstract

    The health status of Q-fever patients after long-term follow-up
    http://www.biomedcentral.com/1471-2334/11/97/abstract

  12. #12 Rogue Epidemiologist
    May 10, 2011

    “DNA Reprogramming Therapist”??? She creates mutants?

  13. #13 LLMD
    May 10, 2011

    So-called Lyme-literate doctors (I’ll sell you anything you ask for, even if it’s dangerous) have their parallels in the CFS industry. But the CFS doctors are more weirdly diverse. There are the Jamie Deckoff-Whoevers who prescribe antivirals and immune system stimulants, but they’re almost mainstream compared to others. There’s one doc who says CFS is caused by low blood volume and will be reversed if you give the patient IV saline daily. So he installs central lines, people get infected through the ports, risking death and heading to the hospital for weeks, and all for what? So people get something the entire world would call a placebo: PBS! It’s hard to blame only the doctor, though. Some patients demand this treatment, risking a fatal infection to treat a non-fatal illness that some people think might be caused by an infection.

  14. #14 LLMD
    May 10, 2011

    By the way, John, general fatigue is not even in the top twenty most common reasons for visiting a physician. It’s an important problem, but it’s not the top problem in health care! Research money would be forthcoming if anyone showed a link between CFS and infection.

  15. #15 John
    May 10, 2011

    It’s not about showing a link between CFS and infection, that has already been shown repeatedly. If you want to watch an overview on the relation between CFS and infection(s), Anthony Komaroff has done several*.

    The current thinking is that CFS most likely has different subtypes and therefore there will never ever ever ever be one distinct cause of ‘CFS’, ie the same pathology and/or abnormality presenting in all cases. This is what keeps allowing people to claim that ‘there’s no link between CFS and X’. There are links between CFS and infection, CFS and autoimmune processes, CFS and immune dysfunction, CFS and low blood volume, etc. but since these abnormalities do not occur in all patients (again the subtype thing) then it leaves a loophole for people to erroneously claim that ‘no abnormalities exist’ in CFS patients and therefore the research money does not get extended.

    I can’t find a reference for CFS and healthcare usage, but I couldn’t sworn that I remembered reading again and agian that ‘unexplained fatigue’ was one of the top reasons for visits to the doctor, even up to 40% of the total. Maybe I’m mistaken.

    The latest research on CFS- Anthony Komaroff
    *http://www.masscfids.org/videofiles/Komaroff/Komaroff.html -54:37

    Overview on HHV-6 and Chronic Fatigue Syndrome- Anthony Komaroff
    http://www.scivee.tv/node/6831 -14:38

  16. #16 daedalus2u
    May 10, 2011

    John, syphilis is an infection by a spirochete that has a chronic phase that affects people who can’t clear it. It was called neurosyphilis and was a leading cause of mental health problems. It was a fatal disorder that killed people in a few years. The first effective treatment was fever therapy. It was the “standard of care” for a couple of decades. It saved thousands of lives and cleared the sanitariums. The person who developed it won the Nobel Prize.

    http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-fever.html

    Neurosyphilis has some similarities to what is called “chronic Lyme”. I don’t think there is such a thing as “chronic Lyme”. I think that “chronic Lyme” is what happens when the immune system and physiology get into a “bad state” that they can’t get out of, and this “bad state” persists long term.

    I think that Fever therapy was a way to get out of this “bad state”. A dangerous and highly risky way.

    My philosophy is that all chronic disorders have to do with the chronic regulation of the physiology that is out of whack with that disorder. If something is out of whack long term, then the physiology that is regulating that physiology has to be out of whack long term. If the long term regulation wasn’t out of whack, then the physiology wouldn’t be out of whack either. Kind of a truism, but the truest philosophies are all truisms.

    I think that just about any infection, if it is serious enough and goes on for long enough can cause CFS. What is important is to “turn off” the immune response that is trying to deal with the infection after the infection has been cleared and have physiology go back to its pre-infection state. Unless that happens, the immune system responses are perpetuated and long term they lead to what is called CFS.

    In neurosyphilis there is chronic neuroinflammation. Chronic neuroinflammation is not good, it causes “brain fog”. If you are in sepsis, you want neuroinflammation because that keeps your brain alive. The neuroinflammation that keeps your brain alive during sepsis needs to be turned down after the infection is cleared. If it isn’t turned down, then you are SOL.

  17. #17 Smurfette
    May 10, 2011

    Chronic Lyme is in worse shape than Chronic Fatigue Syndrome. CFS woo for the most part is still at the research level while Lyme woo is mainly at the treatment level. (Only a very few people are actually taking anti-retrovirals for CFS while most people who go to “LLMD”s take serious antibiotic treatment among other stuff.) I don’t know of any research being done on post-Lyme syndrome but there is respectable research in CFS outside of XMRV.

    I don’t even follow what’s going on in Chronic Lyme even though I got sick when I was bitten by a tick and got the Lyme rash. There are a whole bunch of people who had neither a tick bite, rash, nor recognized test who probably are making it harder for the people who actually have post-Lyme syndrome.

  18. #18 Kemanorel
    May 11, 2011

    Am I the only one that turns the voice of the lyme disease nuts into Ralph Wiggum?

    Dear Miss Hoover, you have Lyme disease. We miss you. Kevin is biting me. Come back soon. Here’s a drawing of a spirochete. Love, Ralph

  19. #19 SYBRcream
    May 11, 2011

    John and some CFS researchers are as sure of themselves as the Lyme doctors, but the data’s thin on both sides. There is only circumstantial evidence that infections are associated with CFS. “X% of CFS cases are diagnosed within six months of an infection” does not mean CFS is caused by infections. Who hasn’t had an infection in the last six months? “CFS is diagnosed disproportionately in the winter months” does not mean CFS is caused by infections. It is one explanation, but affective disorders are another. “CFS has symptoms similar to some infections” does not mean CFS is caused by infections. “Several people in one place complained of CFS symptoms” does not mean an unknown infection is the only explanation.

    The immunological dysfunction caused by a variety of factors is an attractive theory of CFS but there is not much evidence for it, either. The data is from very selective cohorts, the controls are often crap, and the findings are not shown to apply to CFS patients overall.

  20. #20 Smurfette
    May 11, 2011

    “X% of CFS cases are diagnosed within six months of an infection” does not mean CFS is caused by infections. Who hasn’t had an infection in the last six months?

    This is not possible since CFS can’t be diagnosed until you’ve had the symptoms for six months. The data is thin for affective disorders also. With the exception of Epstein-Barr/mono which is still not something people get every six months, the infections that are hypothesized to be associated with CFS– SARS, West Nile, Q Fever, giardia, Lyme– are not the type and severity of infections that most people ever get. They are not the run-of-the-mill infections you are talking about. Nobody says colds are associated with CFS.

  21. #21 SYBRcream
    May 11, 2011

    “This is not possible since CFS can’t be diagnosed until you’ve had the symptoms for six months.”

    Right. That’s why it’s so strange actual CFS researchers propose this. Are you familiar with Leonard Jason and his group? According to them, the winter months have the highest incidence of colds/flu and other viral infections, explaining why CFS is more likely to appear during this time of year.

    Colds, flu, and almost every infection known to science, from run-of-the-mill to too-exotic-to-matter, has at some time been proposed as a cause or marker of CFS.

  22. #22 daedalus2u
    May 11, 2011

    CFS can’t be “diagnosed” until one has had the symptoms for 6 months, but if you have a condition with the symptoms of CFS for 8 months, they say you have had CFS for 8 months, not that you have had CFS for 2 months after you had the symptoms for 6 months.

    Some “infections” are really severe, things like sepsis, SARS and ARDS. When there are persistent effects from really severe infections,

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071317/?tool=pubmed

    The symptoms are often quite similar to symptoms of CFS.

    ARDS can be caused by multiple different infectious agents. My guess is that it is a long and severe infection putting the immune system into a “bad state” that it can’t get out of.

  23. #23 Rorschach
    May 11, 2011

    ARDS can be caused by multiple different infectious agents. My guess is that it is a long and severe infection putting the immune system into a “bad state” that it can’t get out of.

    ARDS is not just caused by infectious agents, trauma is also a common cause. Your “bad state” guess is unscientific nonsense. And there is no need to guess, we know exactly how ARDS happens.

  24. #24 daedalus2u
    May 12, 2011

    So you are saying that CFS is not a “bad state”? That physiology is working just fine in CFS? That it is all psychological?

    I don’t agree with you that CFS is psychological and not due to physiology. There is plenty of evidence that shows that most CFS is due to physiology. Maybe your CFS is due to psychology, but most CFS is not and your rejection of the idea that CFS is due to physiology is not helpful to those who have CFS mediate through physiology.

    If CFS is due to physiology (which it is), and is long term (which it is), then CFS must relate to the long term regulation of physiology (duh).

    If that long term regulation of physiology is not restoring a “good state”, then that long term regulation of physiology must be maintaining a “bad state” (duh).

    If the long term regulation of physiology is not restoring a “good state”, then to “fix” the “bad state” of CFS, the regulation of physiology needs to be changed so that physiology can restore a “good state” (duh).

    What exactly in that chain of reasoning is “unscientific nonsense”?

  25. #25 Rorschach
    May 13, 2011

    So you are saying that CFS is not a “bad state”?

    I said nothing at all about CFS, can you read ??

    Maybe your CFS is due to psychology, but most CFS is not and your rejection of the idea that CFS is due to physiology is not helpful to those who have CFS mediate through physiology.

    Are you on drugs ? I don’t have CFS, I didn’t say anything about CFS, I commented on your incorrect assertions about ARDS.

    What exactly in that chain of reasoning is “unscientific nonsense”?

    Pretty much all of it.

  26. #26 daedalus2u
    May 13, 2011

    I was talking about CFS being a “bad state”. This thread is about chronic Lyme and CFS. The comments I was responding to were about infections causing CFS. I was talking about severe infections, like sepsis, ARDs and SARS, which are sometimes followed by the symptoms of CFS.

    ARDS can be caused by multiple infectious agents, or even by non-infectious agents. ARDS by any mode of causation can be followed by symptoms of CFS.

    CFS is the “bad state” I was talking about, not ARDS.

  27. #27 Vicki
    May 13, 2011

    Daedalus:

    The missing link in your reasoning chain is “regulation” (which I would like a definition of in this context).

    A person can have a long-term physical problem, with ongoing symptoms, because of a specific trauma. How do you get from “part of brain damaged by stroke” or “difficulty walking because of a hip fracture at age 12 that didn’t entirely heal” to “regulation of physiology”? Those are both obviously physical problems, but if there’s a “regulation of physiology” issue there, it’s the result of the trauma, not the cause. I suspect that you could adjust NO levels until the cows come home without curing my friend’s partial aphasia.

  28. #28 daedalus2u
    May 13, 2011

    Vicki, sorry for not being clearer. CFS is symptoms of fatigue (and other things) that persist long term without a known cause. Aphasia due to stroke is known to be due to damage to a particular part of the brain. My comments are directed to conditions that persist long term without a “cause” (this is complicated because a “cause” may be unknown, but in the case of CFS there probably isn’t a “cause” (i.e. something exogenous)).

    Symptoms that persist long term without a cause, persist because physiology allows them to persist. Either physiology does not have the capacity to “fix” them (sometimes the case following brain damage or other physical trauma), or physiology can fix them but is being regulated to not “fix” them.

    Healing is regulated (just like everything else in physiology). Healing proceeds at different rates. Healing is a complex process of many (at least tens of thousands) steps. Those steps all have to happen “in sync”. If the tens of thousands of steps happen “out of sync”, then healing cannot proceed correctly.

    One of the important parts of the regulation of physiology is the allocation of resources. It takes resources for physiology to do anything, and resources that are used for one thing are not available to be used for something else. It is the regulation of physiology that prioritizes resource allocation. If you are “running from a bear”, healing a minor wound is not a priority. If the regulation of physiology was optimal, it would shut off resource allocation to healing minor wounds so that those resources could be allocated to “running from a bear”. You might only get a few more steps, or a fraction of a foot per second faster speed, but escaping from the bear is of infinite value compared to delaying healing while you are trying to escape.

    It is the “fight or flight” state that stops healing and allocates those resources to voluntary activities such as “running from a bear”. We know that something like this happens because “stress” reduces the healing rate of wounds. “Stress” must be affecting physiology in such a way that wound healing is adversely affected. Wounds still heal, the tissues generated during healing match adjacent tissues (pretty much), they still have pretty much the same function, the healing is just slower. Presumably if the tens of thousands of pathways still happen “in sync” such that their fidelity is maintained, but healing just happens slower, presumably the regulation of healing that keeps it “in sync” is still there and the healing is slow because the healing is regulated to be slow. This is an important point. If healing was “out of sync”, it couldn’t happen because cells would (for example) try to divide before they had sufficient resources to do so.

    If we do a thought experiment, what would happen if an organism stayed in a “fight or flight” state indefinitely? Initially not much except there would be greater allocation of resources to ongoing voluntary consumption by muscle. What would happen long term? If resources are allocated away from repair and healing, there will be less repair and healing. With less repair and healing, damage will tend to accumulate.

    What is “fatigue”? Fatigue is a feeling that your body produces when you are exceeding some physiological threshold that physiology is having difficulty maintaining. Fatigue in a muscle is your body telling you that it can’t generate ATP for that muscle as fast as you are telling that muscle to consume it. You can still tell the muscle to consume ATP, and the muscle will still try to do it, and some muscles (like the heart) will continue to consume ATP until muscle cells die. As you do that, the fatigue progresses to pain, and to severe pain. Eventually the pain stops when the cells necrose and can’t send out pain signals.

    In CFS, you can see (with magnetic resonance spectroscopy) that people with CFS at rest have lower ATP levels in their muscles, and those ATP levels get depleted faster and more completely than people without CFS. We should expect to see people with CFS become fatigued faster and to transition to pain faster than people without CFS. It is not surprising that people with CFS have a lower exercise fatigue threshold, a lower exercise pain threshold, and a lower exercise muscle damage threshold.

    My perception of the problem that people with CFS have is that they have been in the “fight or flight” state for too long and can’t get out of it. If they could get out of it, then healing would turn back on and they could recover faster from the damage that has occurred.

    Nitric oxide is one of the signals that turns off the “fight or flight” state. There are many signals that turn on the “fight or flight” state because there are many potential dangers that organisms need to respond to by invoking “fight or flight”. Even immune system activation has some components of “fight or flight”. If you have bacteria floating around in your blood stream, you have to prevent them from attaching somewhere and forming a biofilm or you are SOL. That is what anaphylaxis and sepsis are, gigantic immune system responses, the equivalent of the “fight or flight” response that allocate all available resources to keeping those bacteria from forming a biofilm. Keeping those bacteria from multiplying is more important than trying to heal.

    Low NO is what turns on the immune system via the respiratory burst. Just like low NO is what turns on “fight or flight”. High NO is the regulatory signal that turns them both down and back to “at rest”.

  29. #29 Mary
    May 14, 2011

    I live in tick country..pulled 3 off me yesterday..with that comes lots of “chronic lymers”..followed by the woomeisters..the woosters get chased out of town pretty quickly..

    Now if I could only get my neighbor to stop saying “I can feel the spirochetes wiggling in my brain”

  30. #30 The Analyst
    May 14, 2011

    I’ll let out one of my dirty little secrets. You may or may not remember me, but I have posted here before.

    I have chronic Lyme. I also Have ME/CFS. And the tick came first.

    Let me tell you, the herxheimer reactions from doxycycline were intially incredibly hard to tolerate. In fact, as strange as it sounds, I had to go on IV before oral to tolerate the die off from oral antibiotics. I believe being able to tolerate it without ending up in the ER every dose had something to do with the anti-inflammatory and glutamate suppressing effects of IV Ceftriaxone. I really didn’t want to go IV, but I was running out of options. Honestly, death was a risk that I was willing to take. I was back and forth to the ER all the time (where they did nothing), and my medical bills amounted to hundreds of thousands.

    I lived in the area of the first major outbreak of ME/CFS, but acquired it long after the outbreak.

    Now one thing I can tell you. Antibiotics do not make me well. They make me better. I have hope they can put CFS/ME into remission. I don’t have reacted viral infections that I know of. I actually just took a break from doxycycline to rid of yeast (which I didn’t seem to have too much of from lack of reaction to antifungals).

    I think CFS/ME may end up being yet another syndrome triggered by Lyme disease or related spirochetes. I have confidence that science will figure this association. It’s only a matter of time in my opinion.

    But that being said, I do think there are plenty of patients that mix up ME/CFS and Lyme. I also think there may be plenty of patients that have both. In fact, I think it’s possible that everyone with chronic Lyme has ME/CFS (but not the other way around of course). It actually does make some sense from an immunological point of view.

    If you have a true herxheimer reaction to treatment, you can’t deny the reaction no matter how much of a skeptic you are. I was one of the unfortunate ones that had excess CT scan radiation because of them. Sure there are other organisms that cause can cause herxheimer reactions that may have an association with ME/CFS. Rickettsiae and C. Pneumonia are a couple. However, at the end of the day, these are just names of different bacteria, and if the treatment helps, well, it helps.

    I consider myself a highly educated patient. I understand risks. However, what I don’t understand is why my physician has to be intimidated by medical boards and the like for prescribing something that helps me. I do not want government to interfere with my medical treatment. Please let me do what you disagree with.

    In terms of the ME/CFS aspect, I am pretty classic. There is not much else to explain my sed rate of 0 while having major inflammation. There’s not much else to explain my piss poor bicycle ergonometry test with VO2 gas analysis along with a complete absence of HGH pre/post exercise (as in 0.0). And no a sed rate of 0 is NOT normsl. It is very low and very abnormal. As far as I know, there are five conditions associated with a sed rate this low (ME/CFS, sickle-cell anemia, hereditary sperocytosis, hyper-gammaglobulinemia, hyper-fibrogenemia). Doctors continue to misinformed about sed rates. There is not much that helps me in terms of CFS but daily B12 shots are godsend. However, it could also be helping the neurological damage I now have. Antibiotics do lessen my CFS symptoms, but they do not go away. I no longer have die-off reactions, but infection comes back about 3 weeks off of doxycycline unfortunately. After several years in a tortured body, you can actually learn to differentiate between a CFS flare and the return of a bacterial infection. Sounds crazy that I’d be able to tell the difference, doesn’t it?

    And I agree that the chronic Lyme people go crazy about a tick bite. It is of my opinion that the vast majority will be able to fight the infection(s) on their own even without antibiotics. And then there are the less fortunate that develop the ill-defined syndrome called Post-Lyme Syndrome. I’m not sure I can take that syndrome seriously if they can’t even define the mechanisms causing persistent symptoms that look nearly identical to Lyme disease.

    It’s fun to call people crazy. MS was “faker’s disease”. It was the MRI that finally helped legitimize MS, Parkinson’s, ALS, and Alzheimer’s.

    What’s more crazy is when the patients are right all along and the people who have the most power and influence turn out to be utterly insane.

    I have grown increasingly skeptical of XMRV, but there are a couple new papers you may be unaware of.

    http://www.retrovirology.com/content/8/S1/A219
    http://merutt.files.wordpress.com/2011/05/mikovits_lombardi-publikasjon-mai2001.pdf

    And evidence for persistent infection with Lyme? How about my 83 page document?

    The Case for Chronic Infection: Evidential persistence of Borrelia species post antibiotic exposure in vivo and in vitro

  31. #31 The Analyst
    May 14, 2011

    daedalus2u -

    It’s good to see intelligence! Everything you state is completely correct.

    In my experience, the NO/ONOO- cycle is very difficult to treat. It seems that you can try to treat the gut till the cows come home, and I don’t see many that are greatly improved by that because I believe are immune system is too shot to help regulate our flora. I wish I could stay off antibiotics (doxycycline) longer in order to treat the gut, but I’ve only been able to make it a few weeks or so until having the grab my antibiotics so shit doesn’t hit the fan.

    Hydroxocoblamin may be a potent peroxynitrate scavenger, and perhaps that’s why it can turn off my “fight or flight” response and make me nearly symptom-free for a while (part of a day). But then again I have nearly the same response to high doses of methylcobalamin, so I sit here confused about what B12 is really doing.

    Perhaps they are both just helping methylation/glutathione, but I don’t think that explains my nearly instantaneous response to each shot. If I can figure out what the B12 is really doing for me, I thnk that will give me a lot of clues.

  32. #32 T gardener
    May 14, 2011

    Dr. Horwitz adds, “To take a disease and to extrapolate and say that everyone is infected — that based on alleged clinical symptoms, this is Lyme, even in the absence of data — makes no sense to me.”
    I agree DR Horwitz You could say the same about psychiatrists they claim everyone has childhood abuse or trauma .Which is said to cause ME CFS a disease!
    Psychiatrists have data but it is mainly their own ideas theories and hearsay and flawed research. They don’t want to find biological answers they want to find psychological answers even if there are none to find. Psychiatrists need ME CFS as they needed HIV, AIDS, MS and so many other diseases and it was proved later that these diseases were not psychological but real and serious diseases. How many times must they get it wrong for people to start asking questions about their motives and ideas?
    He adds a cautionary note relevant to Alyssa Goodale’s case:
    “In the absence of a clear diagnosis, you shouldn’t just assign something based on your own theories or probabilities and promulgate a myth. That’s when you take a step that’s beyond what we do.”
    I agree Dr Horwitz You could say the same about psychiatrists .There isn’t a clear diagnosis for ME CFS and they only have theory’s that it is illness beliefs or mainly psychological .They cannot be challenged, no one in the medical world seems to be questioning there science and they have no real science except theory’s to prop up their ideas. They don’t have to prove anything they just have to say it is so for it to be true.
    Ok a clinic might be making money out of Lyme disease and I feel this is wrong. It is wrong to take advantage of the ill; but criticism shouldn’t stop there I would also be critical of others doing the same who are supported by government.
    There are plenty making money out of ME CFS who are having a good life who are not held to account or investigated they are supported by government in the UK and USA . the people pushing Lightning process CBT or cognitive behavior therapy in the UK and graded exercise come to mind and I suppose the people pushing these therapies
    Are not getting big fat amounts of money? And then you have the psychiatrists how much are the making out of this?
    Would I trust a psychiatrist in their power struggle over the ill? With an abysmal history they have in trying to say real illnesses were psychological.

  33. #33 daedalus2u
    May 14, 2011

    Analyst, I think you are misunderstanding my approach. Most researchers who talk about the NO-peroxynitrite cycle do not understand it and have it wrong. The problem of peroxynitrite is not too much NO, it is insufficient NO. Peroxynitrite only happens when there are near equimolar quantities of NO and superoxide. Physiology (normally) regulates itself into either a high NO state dominated by NO (at rest), or a low NO state dominated by superoxide (the fight or flight state).

    Peroxynitrite only happens during the transitions from high NO to high superoxide of from high superoxide to high NO. There are many things that trigger the fight or flight state. Going from a high NO state (where “high NO” might be only 2 nM/L) to a low NO state (where “low NO” might be 0.2 nM/L) is easy. All physiology has to do is increase the rate of making superoxide above the rate of making NO, and the superoxide destroys all the NO and superoxide then dominates. Mitochondria have unlimited capacity to make superoxide. Normally a few % of O2 consumed is made into superoxide. Physiology can increase that until it runs out of O2.

    The transition from a high NO state to a high superoxide state can happen in a heartbeat. That is what your body does when a bear starts chasing you, it releases stress hormones like adrenaline which generate superoxide and which knock the NO level down extremely fast. Your heart starts racing, your liver starts pouring glucose into your blood stream, your mitochondria start generating superoxide to consume NO to disinhibit cytochrome c oxidase to drive the O2 level at the mitochondria low so a high O2 concentration drives a large O2 flux to the mitochondria to make lots of ATP via oxidative phosphorylation. Initially the mitochondrial potential gradient is dissipated as heat, but it is better to have the mitochondria revved up if you might need that high ATP flux to stay a few steps ahead of the bear.

    Switching out of a high superoxide state is much more difficult. The usual source of NO in the body is the various nitric oxide synthase enzymes. They are set up as signaling mechanisms, not to change the basal NO level. When NO and superoxide are both present, peroxynitrite is formed, and that oxidizes the zinc thiol couple in NOS so it becomes uncoupled and now makes only superoxide. This makes the fight or flight state have hysteresis, which you want because you don’t want to drop out of fight or flight easily. But without a positive source of NO, the system can’t overcome that hysteresis and so it lingers in the equimolar NO and superoxide state, never making enough NO to get to the state dominated by NO. This is where the damage of nitrated proteins comes from, not from too much NO, but from not enough. It is the lingering in the transition from low NO to high NO that causes the damage. That damage would be repaired if the NO level was higher and the full transition out of the fight or flight state could be made.

    I think the chronic use of antibiotics is not an effective treatment. I think that any perceived improvements are transient and are due to a Jarisch-Herxheimer reaction from susceptible bacteria in the gut being killed by the antibiotics. The various antigens from dead bacteria are highly immunogenic, they stimulate a Jarisch-Herxheimer reaction, that causes expression of iNOS, that temporary increase in NO causes a temporary resolution of the symptoms of low NO. Then it comes back worse than ever when the iNOS is cleared.

    I discuss this in my blog post on Morgellon’s. Chronic antibiotic use can not be an effective treatment. If the pathogen is cleared, then antibiotics are not necessary. If the pathogen is not cleared, then antibiotics are going to be worse than useless. If chronic antibiotic use has the appearance of an effective treatment, it can’t be due to its effects on a pathogen.

    If CFS is due to XMRV, then antibiotics, chronic or acute would be completely ineffective.

  34. #34 The Analyst
    May 14, 2011

    Thank you for your NO expertise. I have talked to other so-called experts that seem to have varying theories. I don’t know enough to comment on who is right or wrong, or if we are just looking at a lot of theory.

    However you have a couple statements that I disagree with.

    If chronic antibiotic use has the appearance of an effective treatment, it can’t be due to its effects on a pathogen.

    That’s quite a bold statement. With the presence of biofilms and CWD forms, pathogens can persist (especially if one has immune problems that prevent their body from sweeping the stragglers).

    If CFS is due to XMRV, then antibiotics, chronic or acute would be completely ineffective.

    I think you fail to realize that ME/CFS causes immune dysfunction. A virus or bacteria seem to be able to activate infection. It was bacteria in my case, and I know exactly where I got infected.

    HIV doesn’t cause AIDS either. HIV + 1 or more of associated infections does.

    And all that being said, I also had an unknown intracellular pathogen in both my red and white cells observed under my darkfield microscope. However, I can no longer find them on a smear with treatment.

    So the notion that it’s all the gut is just plain wrong.

    I don’t know if I made it clear, but I don’t want to be on antibiotics. I was against long term antibiotics before becoming ill. I also know that if I stop for more than a few weeks all infectious symptoms return and quality of life doesn’t exist. I don’t have much fatigue on antibiotics, but off of them I couldn’t even walk my dog around the block. It’s pretty pathetic. I am stuck between a rock and a hard place. I’ve even considered doing a fecal transplant at home, but I haven’t done that. There was a recent study demonstrating that fecal transplants in CFS have very positive outcomes, so I will keep it in mind.

    I keep in contact with Stanford’s CFS department, and while they haven’t published their enormous CFS pathogens study, I have heard from them that array of pathogens is enormous.

    http://chronicfatigue.stanford.edu

    Once again, thank you for your perspective and your long detailed reply about NO.

  35. #35 daedalus2u
    May 14, 2011

    I have a written discussion of the role of NO in CFS.

    http://www.chronicfatiguetreatments.com/wordpress/treatments/chronic-fatigue-syndrome-nitric-oxide/

    I have links there to the NO literature. The problem of CFS is a too low basal NO/NOx/RSNO level.

    If a pathogen is persisting in the face of chronic antibiotic use, the pathogen is resistant to the antibiotic being used and a different antibiotic needs to be used instead. If the antibiotic is effective against the pathogen, then the pathogen will be cleared and chronic antibiotic use will not be necessary.

    The idea that you can have an effective antibiotic that needs to be used chronically is incompatible with the infection model of disease.

    There is an association of a great many different bacteria with CFS. I do not consider these to be “infections” because they don’t follow the usual pattern that “infections” follow. Normally infections get worse until the infection is cleared or the patient dies. The bacteria that are found in the blood of CFS patients doesn’t get worse and they don’t die from infections.

    Normally the blood stream is completely sterile and minor bacterial injection due to things like teeth cleaning and such are cleared very rapidly. In CFS, there appear to be a higher level of bacteria, as if the clearing is less rapid. People with CFS don’t have blood born infections that progress to sepsis, they have a background of bacteria in their blood that is higher than what occurs in people without CFS.

    My explanation for this is that the immune system is being regulated to be in a “fight or flight” state and so is conserving resources for when physiology “really needs” them. The same way that in the event of an interruption of blood flow to the heart, the heart still keeps pumping, even as parts of it necrose. A beating heart with necrotic spots is infinitely better than a stopped heart with no necrotic spots. The same way an immune system that allows bacteria to persist a little longer is a lot better than being caught by a bear. A slightly lower clearing rate of bacteria and even viruses is compatible with finding all sorts of stuff in blood at very low levels if you look really hard. That does not mean that what ever is found at very low levels in CFS patients is “causing” the CFS. If those very low levels of stuff are not causing CFS, making them still lower isn’t going to cure it.

    The problem is the allocation of resources by physiology. Physiology allocates resources according to signaling. That signaling isn’t magic, it uses signaling compounds, compounds like NO. If the basal NO level is out of whack, then every signaling pathway that uses NO will also be out of whack. The only way that those NO signaling pathways are going to get back into whack is to restore the proper basal NO/NOx/RSNO level. That is not something that is simple or easy or even possible to to artificially. NO physiology is too complex to do something non-physiologic. Something non-physiologic won’t work and will have side effects.

  36. #36 The Analyst
    May 15, 2011

    Thank you for the great resource about NO.

    I was wondering if B12 shots do anything with NO, because it is B12 shots that are extremely effective at halting the fight or flight response.

    We have theories such as Glutathione-depletion methylation cycle block (which I strongly believe in based on my experience), but I have found nothing that truly breaks the cycle.

    When I lifted my methylation block for a few months (requiring no supplementation), the fight or flight aspect died down in a major way, but I didn’t see any changes in immunocompetence. I saw positive changes with my immune system when starting very high doses of B12, high doses of folate, and P5P.

    But like I said, I have trouble stopping doxycycline, and at this point I don’t know how to do it. Everything started with a tick bite that transmitted Lyme (positive IgM through LabCorp, negative ELISA through LabCorp, positive IgM through Igenex, positive IFA through Igenex), Bartonella, and possibly RMSF (equivocal IgG antibodies only). RMSF may have been previous exposure.

    My sex hormones have about doubled on antibiotics. However, I don’t feel like there is much infection left. I feel like there are a few stragglers that somehow multiply within a few weeks after stopping doxy, and if I let it go on too long I end up in the emergency room like I did years ago. It is not a place that I like to be since they treat me like crap, but I haven’t been there in quite a long time now (knock on wood).

    However, it’s pretty clear I have CFS. Sed rate of 0 (huge hint). Terrible results on a bicycle ergonometry test with VO2 gas analysis (bottom 1%). I have no HGH pre/post exercise (0.0). My cortisol does not respond to exercise. And, if it means anything, I lived where the first major documented outbreak of ME/CFS was.

    I would really like to teach my body to get off antibiotics, and I am studying your page on NO. What I got from skimming it is that eating lots of lettuce and spinach may help. In my mind, it sounds far-fetched, but anything at this point is worth a try. My brain (comprehension) isn’t quite the same as it was, so I may have to read it many times over to comprehend. Doctors seem more than clueless these days, and what’s with all these bright engineers getting involved with health? I think by default, engineers are trained to bring new ideas by thinking more out of the box (yet in a very logical sort of way), and doctors more or less operate by a manual. I think the engineers that are getting involved in medicine see the body as more like a machine.

    I have tried meditation, neurofeedback, biofeedback, etc and none of this seemed to have much effect after many months of therapy. Hypnosis seemed to help the best, but it was so temporary and didn’t seem to have a cumalative effect. I feel that it is nearly impossible for me to reach a meditative state when in the past I could relax my brain to a meditative state with ease.

    More suggestions are welcome and appreciated. Any ideas to make quality of life a little better.

  37. #37 daedalus2u
    May 15, 2011

    I have something that is even better, but I don’t want to exploit anyone over it or allow anyone to be exploited (including me). Are you working with a competent medical provider that could do a trial consistent with the Declaration of Helsinki? I have contact information on my website.

    http://nitroceutic.com/

    Send me an email and we can discuss it.

  38. #38 Kiwi
    May 16, 2011

    The Analyst, I’d suggest you just ignore daedalus2u. His whole idea is a perfect example of tooth fairy science. He’s built up an intricate theory that’s scientific sounding enough to be convincing, but any time anyone points out that the idea it all depends on (that NO levels are low in CFS) just isn’t true all he does is stick his fingers in his ears and say that he can’t hear you.

    It really doesn’t matter how much work you put into an idea, if the starting point is bullshit the end will be too. His starting point’s bullshit. I’ll give him credit that he manages to make it sound more believable than most bullshitters do, but that doesn’t really count for much.

    NO physiology is too complex to do something non-physiologic. Something non-physiologic won’t work and will have side effects.

    The sciencey sounding stuff breaks down every now and then though. What the hell is that even trying to say?

  39. #39 daedalus2u
    May 17, 2011

    kiwi, if you actually knew what you were talking about, you would understand what that statement means. Physiology is complicated, much more complicated than you realize, even researchers working in the field often don’t appreciate how complicated it is.

    The reason physiology “looks simple” is because it always seems to “work” (even though we don’t understand how it works). Physiology is self-regulating. When physiology is “working”, all of that self-regulation is working just fine.

    The NO/NOx/RSNO status of someone is really difficult to measure. Those measurements have not been done on people with CFS. If you think they have, give me a link and I will explain why what the link says is wrong.

    Here is an analogy. A computer is run by electricity, but the regulation of a computer is mostly internal and is complicated. Could you “hack into” a computer using jumper cables and a car battery? A car battery is a source of electricity, jumper cables can carry electricity, why don’t hackers use jumper cables? There are lots of spots where jumper cables could be connected on computers. Why won’t that work?

    The reason is that in a computer, electricity is used as a control signal. It isn’t a “more is better” paradigm, it is a control paradigm. A chip needs the right electric potential on the right lead at the right time and for the right duration. The different electric potentials on the thousands of different leads need to change together “in sync” for the whole system to work.

    Physiology uses NO as a control signal. It isn’t a “more is better” paradigm, it is a control paradigm. A cell needs the right NO level at the right organelle at the right time, and for the right duration. That NO signaling is regulated by upstream pathways so as to activate downstream pathways exactly right and “in sync” with all the other billions of cells.

    A computer uses different electric potential levels as a signaling mechanism. There is low and high. If the low and high levels get out of whack, then the electrical signaling will get out of whack too. If the electrical signaling in a computer is out of whack because some levels are too low, and some are too high, you are not going to be able to fix it by attaching a car battery with jumper cables (analogous to a non-physiological intervention).

    The signaling by electricity in computers and by NO in physiology is communication. It is transferring information from one location to another so that the information can be processed further and used to do things.

    In a computer, the information is encoded in zeros and ones and is used to direct the operations of the computer. Even if you had the ability to modulate those zeros and ones at the right scale, unless you knew the communication protocols, the language that the code was written in, the information that was trying to be communicated and for what purpose, all you could do would be to add noise.

    In physiology, the information coding is a lot more complicated and is not well understood. There are many signaling pathways, NO is an important one, but one that has many different aspects. NO activates guanylyl cyclase which then makes cGMP. There are a number of different isoforms of sGC, in different tissue compartments, and with different thresholds, and with different cross-coupling with other pathways. What is important in NO signaling with sGC is the basal NO level, the rate of production of NO, the distance that particular sGC molecule is from the NO source, the presence of any NO sinks in the area, superoxide or lipid, or heme, The duration of NO production and how all of those things change with time. NO is what causes vasodilatation. In the brain, the fMRI BOLD signal is produced by neurogenic NO mediated vasodilatation. That vasodilatation increases the local oxyhemoglobin level which increases the rate of NO removal.

    The NO level that is important in the fMRI BOLD signal is less than 1 nM/L. That is 30 ppt, that is parts per trillion by weight. There are no techniques to measure that in vivo at the time and length scales that are important. If 1 nM/L is “normal”, in CFS the “abnormally low” NO level might be 0.5 nM/L.

    The reason the NO level is low in CFS is because physiology is regulating the NO level to be low. The only way that will be successful in restoring a higher NO level will be to get physiology to regulate the NO level to be higher. Only a physiological method will be effective because physiology will compensate for any non-physiological method.

    If your computer power supply voltage regulation is off, such that the zero and one signals are not being detected properly, you won’t be able to fix it through a non-physiological method, attaching jumper cables won’t work. You have to go in and fix the control setpoint of the power supply. Physiology is a lot more complicated than any computer. There isn’t one supply voltage regulation, there are trillions of them, all with automatic setpoint regulation.

    NO is one of the few signals that does do long range signaling as well as short range signaling. The reason NO is used by physiology for this is because it is a small, light molecule that diffuses rapidly through aqueous and lipid phases and is highly reactive with unpaired electrons. NO is the idea signaling molecule which is why physiology evolved to use it in so many pathways.

    We don’t know exactly what information all that NO signaling is communicating. Without knowing the information and the coding scheme, we can’t duplicate the signals that are necessary, even if we had the capability of regulating NO levels on the time (sub second) and length (sub micron) scales that we know are important at every point in each tissue compartment.

  40. #40 Kiwi
    May 19, 2011

    Wall of text

    So pretty much, you’re saying you don’t need evidence that NO levels are actually low because it’s super complicated and you totally know you’re right without needing any. Got it.

    And also that just raising NO levels won’t do anything. But buy Nitroceutics™, coming soon to a store near you! It’ll raise your NO levels up good. Just what we all need.

    I’m not sure what you find so difficult about the idea that evidence is actually pretty useful, and that just carrying on about how complex things are doesn’t make up for not having any. You just come across like you’re using the word ‘physiology’ the same way Deepak Chopra uses ‘quantum’ and expecting us to be impressed. I’m not.

  41. #41 W. Kevin Vicklund
    May 19, 2011

    The NO/NOx/RSNO status of someone is really difficult to measure. Those measurements have not been done on people with CFS. If you think they have, give me a link and I will explain why what the link says is wrong.

    Some guy has been coming on this site for the past year claiming that those measurements have been done. I’m trying to think of his name. Something like dead2u? No, that’s not quite right…

  42. #42 daedalus2u
    May 19, 2011

    Kevin, I haven’t claimed that the measurements have been done, Kiwi has claimed they had been done and:

    “the idea it all depends on (that NO levels are low in CFS) just isn’t true”

    Ask Kiwi how he/she “knows” that the idea that NO levels are low in CFS is not true?

    When a person is dehydrated, those treating the dehydrated person don’t measure the concentration of water in the person, determine that it is low and then supply supplemental water until the measurement comes up to normal.

    http://en.wikipedia.org/wiki/Dehydration

    There are several different kinds of “dehydration”, and dehydration is a commonly known and commonly treated disorder. However, there are no suggested ways to “measure” how much water is inside someone and by that measurement determine if they need more water or not. What they do is look for symptoms of dehydration, then rehydrate the person according to best practices depending on what else is wrong. If the dehydration is too severe, they will use IVs. If it is less severe, they will use oral rehydration therapy. Less severe still they will give plain water.

    The best and really only effective way to regulate dehydration is to rely on the normal physiology of water regulation. Give people enough water to drink, enough electrolytes to eat and let their own physiology self-regulate their hydration status.

  43. #43 W. Kevin Vicklund
    May 19, 2011

    Liar.

    CFS patients do have low NO levels.

    - A statement made by daedalus2u at least 50 times on ERV and Respectful Insolence within the past year.

  44. #44 daedalus2u
    May 19, 2011

    People with CFS do have low NO levels. Those low NO levels can’t be measured because there are no techniques to do so. The closest thing to a measurement is the fMRI BOLD technique, which measures vasodilatation, which is triggered by NO activating sGC and releasing cGMP and causing smooth muscle relaxation.

    The fMRI technique measures relative blood flow, usually that relative blood flow is used to infer neuronal activation which it usually tracks pretty well. The fMRI BOLD technique works by looking at the magnetic susceptibility of the brain. Deoxyhemoglobin is paramagnetic, oxyhemoglobin is diamagnetic. The way they do that is take the average over the whole brain and then look at deviations from that average. Unfortunately I haven’t been able to find any good papers on fMRI BOLD trying to look at differential blood flow in CFS. The papers I have found are trying to look at differential neuronal activity to explain CFS, not at the physiology upstream that regulates that differential neuronal activity. However people with CFS do have reduced total brain blood flow.

    http://www.ncbi.nlm.nih.gov/pubmed/16494597

    This result was with xenon and MRI.

    http://www.ncbi.nlm.nih.gov/pubmed/10974961

    In this paper they used SPECT. In both cases they found reduced total blood flow. The authors suggest that this means that the symptoms of CFS are related to brain dysfunction associated with that lower blood flow. My interpretation is that the symptoms are related to what regulates blood flow, that would be nitric oxide with low NO causing reduced blood flow.

    One of the leading hypotheses of depression is that people with depression have low serotonin at their synapses. Has there ever been a measurement of serotonin levels at the synapses of people with depression? No, there hasn’t been. The “hypothesis” of low serotonin is a post hoc hypothesis based on the observation that SSRIs relieve symptoms of depression.

    Do proponents of the “low serotonin hypothesis of depression” claim that serotonin levels have been measured at the synapses of people with depression? No, they do not. Does the fact that serotonin levels in the synapses of people with depression have not been measured invalidate the “low serotonin hypothesis of depression”? No, it does not.

    100 years ago, there was no ability to measure insulin, insulin hadn’t even been discovered. Once insulin was discovered, they knew that diabetics needed more of it decades before they could assay blood to measure how much insulin they had. Should they have waited until there were assay techniques to measure insulin in blood before giving it to diabetics?

    Do you want to discuss the idea as an idea? With facts and logic? Or do you want to discuss it at the level of rhetoric with ad hominem?

    I appreciate that CFS sucks. I appreciate that having brain fog due to low NO sucks. I appreciate that being abused by quacks who are pushing bogus crap at people with CFS sucks too.

  45. #45 Jack
    May 19, 2011

    Hey Daedalus,

    I was interested and all but you are flogging something to death here. I think you might now have lost your audience.

  46. #46 Kiwi
    May 20, 2011

    Every study that’s looked at NO levels in CFS has found them either normal or high. Normal here, here, NO metabolites are higher in CFS here, with a much bigger increase after exercise and other researchers claim to be finding high levels but haven’t published anything yet (see the project description here.)

    None of them use magical, impossible-to-do testing techniques so I’m so you won’t be impressed. It’s more than you’ve got to back up anything you’ve claimed though.

    And NO related vasodilation isn’t the only possible explanation for abnormal brain blood flow. Seeing cholinergic abnormalities (and evidence of auto-immunity against cholinergic receptors here) actually have some evidence maybe it’d be worth considering them first. It’s far from conclusive now, but it’s more promising than just babbling on about how it’s so complicated that no one but you could understand it.

    I appreciate that being abused by quacks who are pushing bogus crap at people with CFS sucks too.

    Well, there’s an easy way you could take out one piece of that bogus crap.

  47. #47 daedalus2u
    May 20, 2011

    The first report you cite is for nitric oxide metabolites, not nitric oxide, even though the authors misidentify what they are analyzing for in the abstract. They analyzed for nitrite plus nitrate, not nitric oxide. The normal basal NO level is less than 1 nM/L (how much less is hard to know, see below). The normal nitrite plus nitrate level is variable but is usually around 10 micromoles/L, about 10,000 times higher. Nitrite plus nitrate can easily go 10x higher during sepsis. During sepsis, the NO level of the blood does not even get to 10 nM/L.

    The levels they report are in the normal range, around 10 micromoles/L. The level of nitrate plus nitrate is highly dependent on dietary consumption of nitrate. The report has no mention of dietary restrictions of nitrate containing foods (green leafy vegetables have a few thousand ppm nitrate), so I presume they did not restrict nitrate intake. That would explain some of the variability and the high standard deviation.

    What can be inferred about the NO level, which is known to be no higher than nM/L range by changes in the nitrate level from 8.3 (6.45) micromoles/L to 8.38 (6.92) micromoles/L? Not much. The groups were also not gender balanced. Women have higher nitrate plus nitrite levels (but they are cycle dependent) because estrogen activates NOS and increases NO production.

    The second report is by the same authors who misidentified what they analyzed in the first report. I can only see the abstract but if they misidentified nitrate plus nitrite as nitric oxide in the first report, they are likely to do so again. I will go to the library and try to get the paper. I see nothing from the abstract to indicate they are measuring NO and not nitrite plus nitrate.

    In the third report they specifically say they are measuring NO metabolites and not NO.

    Concentrations of nitrate plus nitrite reflect the production via NOS, ingestion of nitrate in the diet, excretion in the kidneys and consumption by pathways which remain unknown. The half life of nitrate in the blood is about 8 hours depending mostly on kidney function.

    The levels of NO metabolites do not indicate what the NO level is or was. Trying to infer nitric oxide concentration from concentrations of NO metabolites would be like trying to infer O2 concentration from O2 metabolites. The solubility of O2 in water is about 2.3 mM/L (about the same as NO). In plasma, the normal concentration of CO2 is about 24 to 30 mM/L. Could you infer O2 concentration by looking at CO2 concentration?

    The levels of NO metabolites can reflect NO production rate, but the effects of NO are all concentration dependent, not production rate dependent. The only things that are production rate dependent are kinetic issues.

    A very nice paper on measuring the types of NO levels that are important is here.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009818/?tool=pubmed

    This is state-of-the art in NO measurements. These results were presented at the last Gordon Conference on NO. He showed that cells are sensitive to NO levels down to 1 pM/L, or more than 6 orders of magnitude below the micromolar levels of nitrate.

    Confusing NO for nitrite plus nitrate is a common mistake. It is sloppy and imprecise and promotes confusion in people who don’t appreciate that they are different. It is a trivial and sloppy error, sort of like confusing a virus for a bacterium or confusing association for causation. I appreciate that people who do confuse nitrate plus nitrite for nitric oxide don’t know enough about NO to understand the error they are making. I am trying to not be condescending, but it is a trivial error that you are making, one that could be picked up from Google U. The problem is that when people in the CFS field start making these trivial errors, they can block real progress by people who know more about nitric oxide than they do. Sort of like how people who made trivial errors in exercise physiology attributed CFS to purely psychogenic processes.

  48. #48 SAWells
    May 20, 2011

    Daedalus, you’ve posted this: “People with CFS do have low NO levels. Those low NO levels can’t be measured because there are no techniques to do so.”

    Guh?

    As a scientist, I have to tell you that you have lost it. You’re standing on a corner preaching at passersby to come to Nitric Oxide Jesus.

    Christmas presents really are brought by Santa, Santa can’t be caught delivering presents because there are no Santa traps.

    Please stop.

  49. #49 daedalus2u
    May 20, 2011

    Except we do know that NO does exist.
    We do know that NO is a signaling molecule that regulates many hundreds of pathways.
    We do know that many of the pathways that NO regulates are disrupted in CFS.
    We do know that the pathways that NO regulates that are disrupted in CFS are all skewed in the direction one would expect if the basal NO level was low.
    We do know that a change in the basal NO level will change the output of every NO sensor with no threshold.
    We do know that the levels of NO that are important are too low (pM/L) to be measured in vivo on the time (sub second) and length (sub micron) scales that we know they are important in.

    How is that in any way comparable to Santa Claus?

    Did you understand the paper I linked to? The changes in NO concentration that can be measured as having effects on sGC in vitro are pM/L. There is differential signaling due to differential changes in the NO level received at NO sensors at those levels. A change of 1 pM/L in a 10 micron cube is 600 molecules. At those length scales tissues probably shouldn’t be treated as isotropic continua, isotropic lipid has ~9x higher NO solubility than isotropic aqueous phase.

    What should our default be for the NO levels in vivo that we can’t measure? What should we assume they are to try and understand what levels would be important?

    Zero? aM/L? fM/L? pM/L? nM/L? microM/L?

    Or should we throw together the equivalent of PCR with 127 cycles to find something even if it is just noise? Is that what theh CFS community wants? Something, even if it is just noise?

  50. #50 Stephen Wells
    May 21, 2011

    The most fundamental cause of error is the concealment of real ignorance with pretended knowledge, and you’re claiming to know something – that CFS people have low NO – that you also say can’t possibly be measured, and which ergo you can’t actually know.

    Stop doing that. It’s embarrassing.

  51. #51 W. Kevin Vicklund
    May 21, 2011

    We do know that the pathways that NO regulates that are disrupted in CFS are all skewed in the direction one would expect if the basal NO level was low.

    No, we know that you claim:

    1) NO physiology is so complex that you are the only person that understands it

    2) the scientists who have studied it for 25 years are wrong when they claim that CFS symptoms are consistent with high basal NO levels

  52. #52 daedalus2u
    May 21, 2011

    Stephen, diabetics were given insulin because it was believed they had low insulin for many decades before insulin levels could possibly be measured. Are you saying that those who gave insulin to diabetes before insulin levels could possibly be measured were pretending they knew something that they couldn’t possibly measure? Even now, diabetics don’t assay their blood for insulin, they look at glucose and if glucose is high they presume insulin is low and give more insulin.

    Thyroid supplements were given to people with insufficient thyroid activity long before levels of thyroid hormones could be measured.

    Many other compounds have been administered to “treat” various things before there was the ability to measure them. Essentially all vitamins fall into that category.

    http://en.wikipedia.org/wiki/File:Blood_values_for_print.png

    Vitamin deficiency disorders are (in virtually all cases) diagnosed by symptoms, not by blood tests. Malnutrition is diagnosed by symptoms, not by blood tests.

    http://en.wikipedia.org/wiki/Malnutrition

    In the context that I am using it, NO is more like a vitamin, it is something that is needed at a certain level that can’t really be generated by physiology, it requires a biofilm of a certain type of bacteria. Sort of like vitamin K and vitamin B12 are made in the gut and how vitamin D is made in the skin. I consider CFS to be a symptom of low NO, sort of like how rickets is a symptom of low vitamin D. They were able to treat rickets before they were able to measure vitamin D in the blood. They were able to treat pernicious anemia long before they could measure vitamin B12.

    You are not going to understand NO physiology with a few days at Google U. If you don’t understand the difference between plasma nitrate levels and NO levels, then you don’t have even a rudimentary understanding of NO physiology. You do not have the ability to evaluate anyone’s understanding of NO physiology.

    In all detection issues there is the problem of false positives and false negatives. You think that I have latched onto low NO as the “cause” of CFS as a false positive without knowing and understanding the data that I have used to make that determination. Because I do know what that data is, and I know that you don’t, I understand why you think what you do, and why you happen to be wrong.

    The danger of latching onto a false positive is the danger of wasting research funding on a dead end, plus the danger of administering treatments (like HAART) that are harmful and not helpful. That is what is happening with the XMRV idea.

    The danger of latching onto a false negative and rejecting the correct answer too soon is that finding the ultimate solution is pushed off that much farther.

    What “danger” is associated with my low NO hypothesis of CFS? How much funding is being wasted on it? Zero. Right now there is no funding of the low NO hypothesis of CFS, so there is nothing that can be wasted. What dangerous treatments are being administered? None. The only possible treatments are completely non-harmful and none are being used to treat patients with CFS. The only possible “injury” is the narcissistic injury of people whose feelings get hurt because they don’t like the idea. Sorry, but if you don’t like the idea, you need to figure out how to cope with it other than by trashing the people who have it.

  53. #53 daedalus2u
    May 21, 2011

    Kevin, no.

    1. What I claim is that NO physiology is so complex that a couple of days at Google U won’t give you a sufficient understanding. That happens to be true for just about every field. A real expert in the field, looking at the same data that I have looked at, will come to exactly the same conclusions that I have.

    This is the proven consequence of Robert J. Aumann in his paper “Agreeing to disagree”.

    http://cenet6.nsd.edu.cn/userfiles/2010-5-17/20100517195408915.pdf

    Two individuals can’t have the same priors as common knowledge and then not agree on posteriors.

    2. No one has claimed that the symptoms of CFS are consistent with a high basal NO level. If someone did claim that, they would likely be wrong and I would want to look at their technique and reasoning. The papers that have been cited have not claimed that.

  54. #54 Stephen Wells
    May 21, 2011

    Daedalus, either find this real expert other than yourself or stop repeating yourself, please.

  55. #55 daedalus2u
    May 21, 2011

    I have talked to experts in NO physiology who have nothing they disagree with me about, but they don’t want to work with CFS and/or have not been able to get funding to work with CFS in the context of low NO.

    With the degree of hostility that has been directed at me, it is not surprising that people don’t want to work with CFS in the context of low NO. There are other fields where there is less hostility.

  56. #56 Stephen Wells
    May 21, 2011

    I’m not being hostile to you because of CFS.

  57. #57 daedalus2u
    May 21, 2011

    You have completely fooled me as to why you are being hostile.

    I have a comment that is still in moderation. I presume Abbie will release it, unless she has been Raptured. ;)

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