Sunday, September 30, 2018

OMF conference - The Molecular Basis of ME/CFS

For years I have stayed at the Cardinal Hotel in Palo Alto. This is an old-fashioned California hotel. It has a large, high-ceilinged, tile-floor lobby with fireplace and chandeliers. There is no air-conditioning. Cooling is via ceiling fans, the old fashioned way. Early on the morning of the conference, Saturday September 29, I walked across the fantastic landscape of Stanford’s campus, passing various sculptures by Rodin, Segal and Jack Zajac. The campus is littered with sculpture. It was a beautiful early morning walk, full of anticipation.

This is the second annual patients conference sponsored by Open Medicine Foundation. This conference was well-attended, for the second year in a row. Linda Tannenbaum, the driver of this organization, related to me that “this next year is going to be very important” in terms of advances in research. The conference day was preceded by three days of collaborative research conversations. Dr. Ron Davis said that this part of the conference was expanded - in terms of participants - by 50% this year. OMF seems to want to quickly and efficiently broaden their collaborative effort, which already is yielding results. 

The conference was live-streamed so that some 3,000 patients and advocates world-wide could view the day’s proceedings. I write this brief report for those who might be too ill to follow the day-long presentations.

I was pleased to see Dr. Jose Montoya at this conference. He was missing at last year’s conference. 

This was a very interesting day, this last Saturday in September. There was an anticipation of some good news on this research collaboration effort - and this conference delivered on this. From my perspective, there were several research areas to highlight. All are tied together. 

1.Maureen Hanson gave a presentation on Metabolomics and ME. Maureen has worked in this field for some time and was noted as being a strong and independent researcher. Previously she has worked on the microbiome, but now seems to believe that the center of this illness more likely lies in the area of metabolomics. Various studies - including Dr. Naviaux’s - seem to line up in separating ME patient’s metabolic dysregulations from controls. There is hope that studies of dysfunctional key metabolic pathways can be further expanded or replicated and that soon some treatment interventions can be explored. As we already know, a central drug possibility is Suramin. Information on an upcoming Autism trial using Suramin can be found here. The hope is that ME will not be far behind. The search for other compatible drugs continues, researchers trying to match existing drugs or herbals to the metabolic disturbances. Dr. Ron Davis has a small chip that can be used to test existing drugs and herbals against ME patient’s blood. ME patients have blood that is noticeably different from controls, and the researchers look (with this chip) to see what drugs or herbs normalize ME patient’s blood. 

2. The second important area of research was a lecture looking closely at clonal expansion in T-cells. This lecture, presenting research of Mark Davis’ lab, was delivered by Michael Sikora. This young researcher made an excellent presentation, perhaps the best of the day - in a day of terrific presentations - updating the research presented by Mark Davis at last year’s conference. There is clear evidence now that T cells in ME patients expand or replicate in the presence of “something. At the moment, the researchers are not sure why this clonal expansion takes place. The thought is that the T cells do this either in relation to a real pathogen, or as auto-immune reaction (the body attacking self). According to Mark Davis, a similar clonal expansion takes place in MS. It is a big deal to have proven and observed this clonal expansion, and it will be a big deal to find out why this happens. Again, the hope is that this discovery might lead to some specific treatments. 

3. Closely related to this is the work of Dr. Jerad Younger, who studies inflammation in the brain of ME patients. His belief is that the ME brain is in an inflamed state. Dr. Younger showed  scans demonstrating that ME patients have abnormal inflammation in the brain (compared to controls). He also is able to measure increased temperatures in parts of the brain that are abnormally inflamed. In listening to Dr. Younger, bells and whistles went off as he described the delicate situation of these patients with brain inflammation. It sounded like my daughter’s desperately precarious situation. Any stimulation - the mildest insult - makes the patient sick. The consequence is that the patient, like my daughter, can be subject to repeated daily episodes of feeling sick. Dr. Younger, who has done research regarding LDN in Fibromyalgia, says that LDN might be able to quell this inflammation somewhat. He emphasize that this is unproven in ME. He also postulated that trying to cool off the brain physically might be of benefit, but I was not sure what he actually meant.

4. The last important section was a presentation by Dr. Robert Phair. Dr. Phair is relatively new to this research group and has been pursuing his own hypothesis, what he calls, “a new way of looking at ME”. Dr. Phair started his presentation by citing Dr. David Bell’s 1994 book, “The Doctors Guide to Chronic Fatigue Syndrome”. He also cited Hillary Johnson’s seminal book "Osler’s Web", as being particularly instructive relative to characterizing the several well-known outbreaks of this illness. This outbreak history gave Dr. Phair a key. Dr. Phair’s first foray into examining his hypothesis of a "metabolic block" focused on one pathway involving energy (ATP) production, particularly the relationship of tryptophan to kynurenine. Dr. Phair proceeded to illustrate that this pathway is broken and that the block exists. Again, this effort offers a potential opening for treatments. More work needs to be done, including work on other pathways, but this result has arrived pretty quickly, after only eight months of work.  Four new collaborations on this project have emerged from the scientific discussions. 

Additional lectures were given by Wenzhong Xiao, Jonas Bergquist, Alain Moreau, Ron Tompkins. I would have liked to hear an update from Dr. Naviaux. 

Professor Ron Davis spoke at several times, at one point presenting OMF’s work on developing a biomarker. He also gave insights into the unpredictable, yet positive, benefits of having a three-day working meeting with many willing collaborators. He gave examples of “what getting these people together means”. 

Davis went on to describe the phenomenon of Trytophan being high and Kynurenine being low. Low Kynurenine is a problem. Kynurenine makes NAD, which controls many processes in the body. Kynurenine controls the immune system. Without kynurenine you cannot suppress auto-immunity. “Does that sound familiar?”

The lectures will be on YouTube soon, reflecting OMF’s model of sharing information. Viewing these videos, if possible, is worth the effort. Observing these lectures with their slides and question and answer sessions is a good way to "improve" this modest attempt to get some information out to those who might want it. 

The bottom line is that much has happened since last year's conference. OMF is moving fast but they need more money to hire more researchers. Please consider supporting their work. 

Friday, August 11, 2017


This post is preceded by 2 posts on sleep. These three posts are designed to be viewed together.

I started to get interested in medicinal marijuana about five years ago. There were a few examples of ME/CFS patients who used various marijuana medicinals for pain, inflammation and sleep.  Most resided in states where medical marijuana was legal or about to become legal.

Cannabis has over 70 cannabinoids of which the most well known is THC, the psychoactive part of the plant.  A second component or cannabinoid has recently received a good deal of attention. It is CBD or cannabidiol. CBD is believed to have various medicinal activities.

The Federal government continues to list marijuana as a schedule 1 drug. One very great consequence of this is that research into marijuana is severely and intentionally restricted. With more states legalizing marijuana, the bigger states are starting to do some research into this plant. Research continues in Israel, Spain, UK and Italy, but it is, predictably, underfunded.

Anyone who wants to engage this subject is going to have to proceed on their own, guided by trial and error.

In reality there are two allied plants, cannabis and hemp. Cannabis is loaded with THC, while hemp has very little. Both have a great many other cannabinoids including CBD, CBN, CBG, and CBDa.

CBD from marijuana has always been touted as the gold standard of CBD. Some propose that in order to be effective CBD needs to have a certain amount of THC with it. Marijuana CBD is restricted to states where marijuana is legal. It appears that Mary's Medicinals makes good products. 

About five years ago, there were only a few companies that produced CBD from hemp. These CBDs were legal, but their quality was challenged by many, including the marijuana CBD makers. Also the FDA objected to the claims of some of these hemp CBD producers.

It remains to be determined if hemp CBD is as good as marijuana. However, certainly things have radically changed in the last few years; there has been an astonishing amount of sophisticated hemp CBD that is available through the Internet. Hemp CBD is legal in all 50 states.

There is a growing body of positive anecdotal information of hemp CBD use, but there is very little of what one might call real science. This might change but I wouldn’t hold my breath. The main claim for both forms of CBD is that they reduce pain and diminish anxiety. Hemp CBD has been called “calming drops” by my own daughter.

The question remains. Will CBD be useful to ME/CFS patients? We are about to find out, as more patients are giving this a try. As with almost everything with this illness, the process is wholly trial and error. Additionally, every treatment must be individualized.

The present choice in high grade, organic hemp CBD is quite surprising. At one end one finds Mary’s Nutritionals pure CBD. This has been heated and refined to take all terpenes and additional cannabinoids out of the solution, leaving only pure refined CBD oil. This oil is at the expensive end of the spectrum. One can find similar CBDs at RSHO with their RSHO-X - no trace of THC, pure organic hemp CBD.  At the other end of the spectrum is raw unadulterated, unheated hemp CBD, also organic, some grown in the US.  A good example of this can be found at Nu-Leaf. These products have CBDa and CBD along with terpenes and all the cannabinoids in the hemp plant, producing what is referred to as the "entourage effect". The entourage effect is the supposed but unknown interaction of all the cannabinoids and terpenes working together.  In between, and cheaper, is a heated, partially refined CBD that can be settled on in various places. Read about this at Endoca.

As there are arguments as to whether THC is necessary to make things go, so there are arguments between the use of pure refined hemp CBD oil versus the raw plant oil with all the terpenes and host of cannabinoids that work together to create the “entourage effect”. The positive way to look at this is that there are many options to try.

In addition to oil, there are pastes, extracts, pills, crystals, gels and suppositories. This industry has exploded. Put a Google alert on hemp CBD and start reading.

The rationale for using CBD in ME/CFS lies in the thought that ME/CFS might be connected to an Endocannabinoid Deficiency. Here is an article on the Endocannabinoid system. Here is another one. Finally, here is an interview with Dr. Ethan Russo on CBD and Endocannabinoid Deficiency.

The study of the Endocannabinoid system can be said to have begun by the Israeli scientist Raphael Mechoulam with the discovery of the psychotropic cannabinoid THC in the mid-1960’s. (Dr. Mechoulam remains the foremost marijuana researcher in the world.) Further research identified the brain receptor CB1 in the early 1990s, quickly followed by the discovery of a second receptor CB2 located throughout the human body. With these discoveries the Endocannabinoid System was identified, leading to discoveries that this very system helps regulate a host of processes in the body - and the awareness that deficiencies might have some connection to chronic illness. 

With so many dysregulations and disconnects in this strange illness of ME/CFS, it is worth considering that these patients suffer also from Endocannabinoid Deficiency System. The supposition is that these deficiencies, these Endocannabinoid deficiencies, can be corrected – with CBD or other cannabinoid items. Certainly the symptoms of Endocannabinoid Deficiency seem to shadow ME/CFS symptoms.

There is additional study and use of other cannabinoids from hemp and cannabis for seizures, sleep, pain, anxiety, migraines, wound healing, and the rest. You name it and some cannabinoid is reputed to help treat it. THCa is in the raw cannabis plant. If one heats THCa it converts to THC. The straight marijuana plant can be treated in a cold fashion (unheated) - and the THCa preserved. THCa is a non-psychoactive compound, which is reputed to have many of the qualities of CBD. CBN is another interesting cannabinoid. CBN can be increased in the marijuana plant material by aging the main product, exposing it to sun and light for a long time – months. Converted into a medicinal, either a tincture or a salve, CBN is reputed to have high sedative effects. Others say that the sedative effect of this aged product comes from the aged terpenes. CBG is another cannabinoid that is gaining interest, also for the same properties – its calming and sedative properties.

My main interest at the moment is in these various cannabinoids as sleep enhancing agents. Not to beat a dead horse, but a good sleep sensor is very helpful in seeing changes wrought by different compounds in different arrangements. A pulse and oxygen saturation monitor also could be helpful, in conjunction with low-dose oxygen. A sleep sensor can separate out and determine sleep initiation, sleep duration, length of sleep entirety or sections of sleep. This can be immediately obvious and adjustments made based on the sensor readings.

So the world is working its way back to cannabinoids, which does not make everyone happy. There is a great battle going on, and it is not difficult to identify its outline and terrain. Where this will go we do not know. The surprising thing is that cannabinoids have been used as medicinals for thousands of years before being put out of business in the US in 1934 and then really put in the slammer by Richard Nixon in the mid-1970s.

Both ME/CFS physicians Paul Cheney and John Chia have used CBD with their patients. 

Here is an additional blog that has information on CBD.

What is written about is educational in nature. It is not medical advice. Please consult your physician (if you have one) for medical advice. 

Friday, August 4, 2017

Sleep in ME/CFS

The sensor helps gather some important objective information - when the patient goes to sleep, when she is awake, her heart rate and movement, when the patient awakes. One can quibble that the measurement of various types of sleep are only estimations, but I maintain that over time one gets an idea about what one might be able to do to improve sleep. Certainly, over time, one can decipher a better night's sleep from a worse night's sleep. One can detect patterns of improvement or regression. One can ask why and try various supplements or drugs. 

Let me make some suggestions as to what might help. None of this should be taken as medical advice. I am not a doctor and have never had the slightest interest in being one (although I have taught a number of terrific doctors!).

Vasoactive Intestinal peptide
Vasoactive Intestinal Peptide (VIP) is a neuropeptide with a host of activities in the human body. In ME/CFS, it was studied by Don Staines about ten years ago. Very little follow up study in ME/CFS has been done of this neuropeptide. One wonders why. Both Dr. Paul Cheney and Dr. Ritchie Shoemaker used it in their practices with varying success (until they retired). Dr. Shoemaker describes it here, as it applies to CIRS.  It appears to have broad activity. Dr. Cheney believes it helps reboot the deranged sleep cycle in the illness. The idea is that it needs to be taken from 9-18 months to have effect. VIP is taken in very small amounts by mouth several times a day. VIP can be procured by prescription from one compounding pharmacy in the US. Various testimonials can be found on VIP activities in ME/CFS by searching online, although not a whole lot is available. VIP is a vasodilator that seems to potentiate other drugs or supplements. It is believed to help with sleep. As part of the Cheney protocol it is described here.  This is from several years ago. Testing VIP levels can be done at ARUP labs. Other labs appear to be unreliable.

In the last two or three years, I have learned about transdermal or liposomal delivery of various items, including B12. B12 can be very effective when injected, either methyl or hydroxyl or both. However, for certain patients, injections present a real problem. One very nice solution is the transdermal b12 oils, made in Australia. They can purchased through This company makes an adenoysl B12 spray as well as both methyl and hydroxyl and various other combinations, including a transdermal b-complex. The oils are delivered by a predetermined sized spray to be rubbed directly on the skin. There are several discussions of b12 oils on Phoenix Rising. This product increases B12 on an OAT test. B12 is closely linked to B2. One can also buy or make several different liposomal b12s. Liposomal products generally are better absorbed. Taking methyl b12 can help with sleep.

A number of years ago I began looking around for ways to get magnesium in the body other than through pills or injections. I came upon a magnesium sulfate cream made by KirkmanLabs. This is effective for short durations, perhaps an hour or two. Ultimately, I explored how to make transdermal magnesium myself. This could be both cheaper and allow me to make larger amounts. Through the internet I have learned to make a transdermal magnesium chloride cream that allows a serious uptake of magnesium. It is especially helpful if applied prior to sleep. It is relatively inexpensive, and it works. Applied in enough volume to the skin, magnesium is critical in putting a person on the road to sleep. Its duration of activity seems to be two hours at the most. To further increase magnesium, I have learned to make emulsified or liposomal products.  Specifically, I have learned how to liposomalize magnesium threonate. This really helps taken prior to sleep or during the night, and it lasts considerably longer than the lotion. In my view, magnesium is a key to solid sleep. Various liposomal magnesium products can be bought online or from compounding pharmacies. They tend to be expensive. 

5-htp, SAM-e, Uridine
It is very difficult to determine what might help slow wave sleep. A few supplements have some anecdotal testimonies. Among these are 5-htp and SAM-e and Uridine. All are mentioned as increasing deep or slow wave sleep. Both of these can be put in a protocol and tested against a sleep sensor. One can quickly determine in a few weeks whether a particular item might improve sleep. 

Piracetam is a prescription drug in Europe. In the USA, it is available as a supplement. It was the first of what are known as nootropics. Piracetam is widely studied but not in ME/CFS. It is hard to believe that there is so little research on this substance in ME/CFS. However, there is some good  information on Piracetam on various sites. The first is cfsremission and can be read here. Scroll down on this page by Maija Haavisto and read what she says. The third is included in a book and website by Erica Verrillo here. In certain cases, Piracetam can have a profound affect on sleep. As is usual, the opposite can happen also. Two more widely employed studies on Piracetam and oxidative stress can be found here and here. Piracetam can be liposomalized. 

Other items
Other items that are worth testing for sleep are GABA/theanine liposomal spray, glycine, l-ornithine, melatonin, valerian root, bacopa, and others. All need to be tested as trial and error.

Several drugs are suggested for restoring deep sleep in ME/CFS. Among these are Trazadone and Xyrem. I don’t not know much about Trazadone, but I myself would be worried about a dependency on an anti-depressant. Many drugs are double-edged swords. Some believe that severe ME is the result of negative drug reactions - and. from my own situation, I would tend to believe this. Xyrem is a miracle drug for some patients, with ME/CFS and otherwise. It was studied a few years back by Klimas, with favorable results. Xyrem is capable of putting some patients into regular and sustained deep sleep. It can bring significant benefit to ME/CFS patients, provided they can tolerate the drug. As with many drugs, Xyrem appears to lose efficacy over time - and it also seems to have various unpleasant side effects for some, including heightened daytime anxiety and driving hunger. Xyrem is heavily regulated and controlled by Jazz Pharmaceuticals, which holds a monopoly. Back when it was held by Orphan drugs, Dr. Enlander was interested in doing trials for ME/CFS. In the 1990s, GBH could be procured in a health food store for $30. Xyrem now costs thousands of dollars. It is prescribed mostly for Narcolepsy and Cataplexy.  By definition one cannot have narcolepsy without cataplexy. In my opinion, ME/CFS is a cataplexic illness. All patients should qualify for taking this drug. I have seen this work in certain patients and it is impressive. In 2009, Klimas was onto this treatment, but she seems to have been discouraged by the difficulties in procuring it. 

Low dose oxygen
For years ME/CFS patients have taken nasal oxygen. Generally it seems to relax patients and help prepare them for sleep. Oxygen at higher levels is believed to be toxic to ME/CFS. At lower levels it works in a paradoxical fashion, as recently described by Dr. Paul Cheney. The closer one can take low-dose oxygen to sleep time, the more effective it can be. Certainly a trial of taking low-dose oxygen during the first part of the night is warranted. It seems to blunt awakenings caused by a stress response to low oxygen saturation. One can get a hint of this on a sleep sensor program. More particularly, oxygen saturation can be measured by a simple device placed on the finger and wrist at night. This device measures oxygen saturation and heart rate, so that the problem can be identified. It appears that a good number of patients respond well to low-dose oxygen during sleep. 

And then there is hemp and marijuana based CBD
These CBDs, along with CBN and THCa, and maybe CBG are incredibly promising as a sleep treatment in ME/CFS. I will write a bit about this in my next post.

Sunday, July 23, 2017

Sleep tracking and ME/CFS

Most people would agree that good, solid sleep is essential to recovery, or stability, in ME/CFS. Some doctors talk some about sleep, some not at all.. My idea has always been – Correct the sleep and set the stage for recovery or betterment. This is easier said than done.

One basic question is how do you get objective information on sleep quality? If the patient is able to move, one could have a sleep study done. But this is only a short cross-section slice of a big picture and it is difficult to do every night. Believe it or not, sleep studies are different on back to back nights. To be really effective, you would have to do a string of them and maybe every month. 

So - what is the next best option, something that is a little more practical? My son Peter bought his sister a Beurer SE80, a home use sleep sensor. This sensor is one of a number that are on the market. All of these type of sensors use movement, respiration and pulse in tracking a patient’s sleep. There are more sophisticated items coming down the line. It is a rapidly moving field so one needs to pay attention.

The Beurer SE80 is a six-inch flat disc, placed under a mattress, near the heart of the patient. It is plugged into the wall. It records its information on a device - an IPhone or IPad or other - via Bluetooth. The recording device has to be within 25 feet of the sensor. Various reviews of the Beurer SE80 complain about the program, that it doesn’t archive, blah, blah, blah. In my opinion, it generally records and makes available the necessary information. It is not perfect, but it is very useful. 

The sensor is turned on when the patient is about to go to sleep. The sensor detects when the patient falls to sleep. The sensor tracks when the patient is asleep, when the patient is awake, or away from the sensor (out of range, from movement or getting out of bed). Through movement, breathing  and heart rate, the sensor calculates (guesses at?) estimates of deep sleep or Slow Wave Sleep, REM and what they call light sleep. It gives results both in a percentage and time breakdowns. It tracks average overnight heart rand respiratory rate

In the roughest sense, one can get an idea when the patient goes to sleep, how long they sleep, when they awake, when they get out of bed, when they go back to sleep and when the sensor shuts off. On a good night, a patient might turn the sensor on at 11, go to sleep at midnight, move immediately into slow-wave sleep, cycle through periods of REM, and wake up. The time awake is noted and records when the patient goes back to sleep. My particular patient sleeps in stages, first sleep, second sleep and often third sleep (in the morning). Certainly, everyone is different in this regard. 

The first question one might ask is how accurate is this device? How accurate especially are the deep sleep and REM categories? To this I can only answer, I do not know. 

However, like with pedometers, I have learned to pay more attention to consistency or predictability than accuracy. It you wear a pedometer - like the Fitbit - every day, day after day, one gets the sense of consistency and reliability. Anyone with this illness who is able to move should be on a Fitbit pedometer. It is the only objective device available to ME/CFS patients, a device that will track regression and improvement. I remember standing in astonishment with the tall Rituxamab fellow, as he laughed at my suggestion to use a pedometer on his Rituximab patients. His first argument was that it was too expensive. Then he said that it wouldn’t work. I just turned away, wondering where this guy left his brain?

We started using the Beurer sensor a year ago now, using it every day. About 10% of the time it does not record all night, for various reasons – thunderstorms, internet or Bluetooth failure, low battery - and sometimes for no apparent reasons. 

Over this time, a year, I have gotten a pretty clear picture of my patient’s sleep, both in its ups and downs. 400 sensor reports gives you a feeling of what is going on. With the information gathered from this sensor, I seek means for achieving improved sleep. 

Next up, some idea about sleep betterment in ME/CFS.