Dr. Anthony Komaroff’s Responses to Follow-Up Webinar Questions

image001On November 10, the Solve ME/CFS Initiative hosted a webinar with Dr. Anthony L. Komaroff, Simcox-Clifford-Higby professor of medicine at Harvard Medical School and senior physician at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Komaroff has followed up with his responses to the numerous questions that were unable to be answered during the webinar due to time limitations. To watch the full video of the webinar, go here.

Q: To what extent are different researchers with their different focuses converging on a single, generally agreed explanation for the cause of ME/CFS and the mechanism or mechanisms that maintain it?

A: Abnormalities involving multiple organ systems have been identified, and there are theories that could tie together many of those abnormalities, but proving any of those theories is going to take much more work.  In the Webinar, I discussed one theory, about how low-grade inflammation in the brain, or inflammation elsewhere in the body that could theoretically lead to low-grade inflammation in the brain, could be responsible for the symptoms of ME/CFS.

Q: How soon will we see approved drug treatments, and which will be the first to be approved?

A: For drug companies to pursue a drug for ME/CFS, they need a target for their drug to shoot at.  While many different biological abnormalities have been reported in people with ME/CFS, it’s not clear which are central to the illness―and, therefore, good targets.

Q: In light of Fluge & Mella’s success with Rituximab and Cyclophosphamide they commented that in those that have had significant improvement they notice that the gut issues go away. Wouldn’t that suggest that the gut is a secondary issue in this disease?

A: Fluge and Mella, themselves, have not said that these two treatments are “successful”.  Indeed, they said at the IACFS/ME meeting in Fort Lauderdale in late October, 2016, that doctors should hold off using those treatments at least until they complete their current study―which will not end until late 2017. They also said that the treatments do not work for a substantial fraction of patients with ME/CFS. So let’s wait for more evidence before assuming these treatments will help patients―and hope that they prove to be helpful.

I don’t think the research Fluge and Mella have reported thus far says anything about the possible role of the gut microbiome, if I understand your question correctly.

Q: Your portion of the Grand Rounds was excellent, but others were quite not. Why did the Grand Round include recommendations of CBT and GET?

A: If you are referring to Public Health Grand Rounds at the CDC in February 2016, you would have to address your question to the speakers who made that recommendation.

Q: Could the lactic acid increase be due in part to deconditioning?

In most of the studies I cited, the healthy control subjects to whom the ME/CFS patients were compared also were similarly deconditioned.

Q: Were the level of cytokines in the spinal fluid different for patients who had been sick for less than 3 years as well as more?

A: That’s a good question.  The study of cytokines in the spinal fluid did not include enough patients (some ill less than 3 years, and some ill more than 3 years) to answer that question.

Q: Do you think that the electron transport chain is damaged in ME/CFS?

A: Some studies have suggested that its function is impaired.  That functional impairment, if true, doesn’t require physical damage to mitochondria, however, if that is the thrust of your question.

Q: Has anyone examined whether there is a correlation between severity of CFS/ME symptoms with serum levels of histamine? I have evidence of elevated serum histamine in one test and when I do things that cause the release of histamine (e.g. ingest alcohol or sorbitao) the symptoms get worse. I have not seen anything about this in the IOM report or in the other literature that I have been well enough to examine.

A: There is not enough research to answer this question.  During the Webinar, Dr. Nahle referred to a recently-published scientific study (not of patients with ME/CFS) that raised the possibility that histamine biochemistry could be involved in ME/CFS―but this is just a theory. The study was recently published online in Nature Genetics (doi:10.1038/ng.3696).

Q: What is the latest information about using Low Dose Naltrexone as a medicine to help those with ME/CFS?

A: I’m not aware of any large, carefully conducted randomized trials of LDN in ME/CFS.  I hope there will be.

Q: Is celiac disease a common factor in ME?

A: No.  Very few patients with ME/CFS also have full-blown celiac disease.  There is another condition, “gluten sensitivity”, which medical science is only beginning to understand.  I’ve seen some patients (but only some) who have ME/CFS and also appear to have gluten sensitivity.

Q: In the sickness behavior model, whether it is due to persistent infection or persistent inflammation, how could you explain the defect in energy metabolism outside the brain? Is there some sort of signal that the brain sends to mitochondria in order to produce less energy?

A: That’s a very good question, and a recent paper in the journal Cell (doi: 10.1016/j.cell.2016.08.042) suggests that such a signal from a “sick” brain to mitochondria outside the brain is possible.  To be clear, this study was not of people with ME/CFS: indeed, it was a study of a worm.  But that worm has taught us a lot about human biology.

Q: Has this presentation been given to NIH?

A: I spoke at NIH in June 2016, and made some of the same arguments.

Q: Would drug therapies that reduce brain inflammation help with symptoms?  What about gut anti-microbe therapies. Even off-label

A: Theoretically, such therapies might help.  But “inflammation” is a big, complex process, and finding the right inflammatory molecules to target will not be easy.  And until we have solid evidence that the gut microbiome plays a role in ME/CFS―and just what abnormalities in the gut microbiome are responsible―it won’t be easy to develop effective treatments.

Q: What is the simplest way to repair the gut microbiome – beyond Probiotics and whole foods which most of us already take?

A: We don’t know enough yet to answer that question.

Q: Have there been any studies done that compare test results during remission and during relapse?

A: There have not been enough such studies to say anything definitive.

Q: Why does my well-known neurologist still not use the term ‘ME’?

A: The term “ME” is unfamiliar to most doctors in the U.S.  On the other hand, the term “CFS” is now familiar to most U.S. physicians.

Q: I did not hear any study information that addresses the onset of the illness. Are studies not being done that include historic information being collected that would identify any common denominator with the beginning of the illness? ie flu, immunization, environmental exposures

A: There are many epidemiologic studies that have studied how the illness starts.  My summary of these studies is as follows. Studies conducted among patients who come to medical practices that specialize in ME/CFS find that the majority of patients report that the illness started with some sort of “infectious-like” illness.  In community-based studies, where research teams identify people in the community with ME/CFS who may never have sought medical attention, the fraction who say they had an “infectious-like” illness at the start is somewhat smaller.

Q: I live in an area where few doctors recognize ME/CFS as a genuine disease.  Can you suggest ways to increase awareness of this information in this area (Wilmington, DE.)

A: I would suggest that they read review articles about ME/CFS in the medical literature.

November 16, 2016
  • Nikoli McCracken

    I’ve had CFS/ME since 1981. After five years, my adult children didn’t want to hear any more about ‘Mom’s mystery illness.’ But then, both of them, one by one, got it. My daughter began with Mono, then just never got well. She progressed, through the years, to MS. My son, has primarily fibromyalgia, result of a motorcycle accident. Both have since apologized to me for not understanding that I didn’t fake an illness.
    I am now 79, have a reasonable level of comfort, but even slight extra exertion can wipe me out for several days. Early on, doctors kept saying to ‘do physical therapy.’ Being a perfectionist, I tried to comply. The result was always a flare-up. I don’t do regular exercise anymore. It’s an invitation to more pain, and I am not a masochist! I do, during the summer, swim in our town’s ‘ol swimmin’ hole, which is 84 degrees. I can still swim like a fish, and it is the one exercise I can both enjoy, and not get hurt. I still have dizziness upon standing. IBS is a constant, but I keep it reasonably controlled by taking meds first thing in the morning, and then I CAN’T eat for two hours. After that, it’s OK. I cannot shop for myself unless the supermarket (Walmart, Safeway) provide handicap scooters. They are a godsend. I can and do still drive, but must rest up for several days if I drive any distance.
    I still collide with doctors who don’t believe the illness is ‘real.’ So do my adult kids, both military veterans, when consulting VA doctors. Quite a few of the medications given to others, and which work for them, don’t work for me. Elavil turned me into a zombie for six days! Prozac made me suicidal. Xanax works to help me sleep, and Flexeril helps with muscle pain. I also have to take Potassium, as Slo-K, or I get big Charley horses in my muscles. One good thing with Xanax: I used to ‘startle’ awake on other meds, and that caused me to jerk an arm or leg – HARD. Which hurt my already-damaged spine. (Three drunk drivers over 10 years) One doctor forced me to wean off Xanax. When I did, the startle thing came back. One medication with a GOOD side effect. It also gets rid of the Restless Legs syndrome – and made it unnecessary to take Klonopin. I cannot take most opioid meds – only Demerol for migraine. I don’t need to take it often. All other opioid meds make me feel ‘wired’ and jittery. I hate the feeling! I cannot consume alcohol, not even in the smallest quantity. Same effect; wired. Not worth drinking! No problem. I don’t smoke, drink, do drugs, or abuse my medications, and never have. So, I keep hoping for a cure. But of course, first we have to find a cause. Blessings on everyone who suffer this awful illness – which a friend and I abbreviate in emails as ‘the DD’ – for damned disease! Anyone who wants to use that, is welcome.