Sleep Studies, Disorders and Treatments with ME

 

In 2015 I detailed the best sleep aids for ME according to ME/CFS specialists and my own experiences. Since this date I have been on a rollercoaster journey in search of some much needed refreshing sleep. This article will cover my travails as well as what I have since learnt regarding sleep studies, Restless Legs Syndrome, Upper Airways Resistance Syndrome, good sleep hygiene and sleep supplements.

 

Sleep Studies for ME

Dr. Klimas, Dr. Bateman and Dr. Levine all recommend that sleep disturbed ME/CFS patients get a sleep study performed. Sleep studies fall into two categories; firstly those performed in a specialist sleep laboratory, most often in a hospital room and secondly at home sleep studies. Sleep laboratory studies involve an array of sensors being placed all over the body and a glut of gadgets. They occur overnight- most commonly in a hospital bed and can potentially identify a range of sleep disorders from: sleep apnoea, upper airways resistance syndrome, restless legs syndrome, insomnia, sleepwalking, REM disorders to other sleep issues. Your heart rate, oxygen levels (determined through a sensor, not a needle), eye movements, breathing rates, leg and arm movements and snoring are all monitored as well as the different stages and lengths of your sleep cycle. A narcolepsy test commonly requires that patients complete the in-laboratory sleep study and then subsequently stay for the next day testing process.

Contrastingly to an in-laboratory sleep study, a home sleep study takes place in the comfort of your bed and has a smaller scope of instruments attached to you. It’s primarily used to diagnose sleep apnoea. The advantage of this sleep study is that people tend to sleep more comfortably in their own familiar bed as opposed to a foreign bed and surroundings of a hospital/sleep lab. The downside of this type of sleep study is the lack of scope of instruments used means less sleep disorders are diagnosable.

Sleep apnoea and some other similar sleep disorders have a large overlap of CFS symptoms (minus post-exertional malaise). Snoring, a large neck, being overweight, nasal obstruction and unrefreshing sleep are just some of the signs. Some ME patients may have ME and a comorbid or independent sleep disorder that is making their illness even more challenging. Overall, sleep studies find that around 1 in 5 ‘CFS’ patients actually have a sleep disorder causing their symptoms. These sleep disorders can be readily treated.

 

My Sleep Study Experience

At the beginning of 2018, I asked my doctor for a sleep study and cautioned them that I didn’t believe I would sleep during the night due to the array of instruments attached to me, the new environment and my typical poor sleep. My doctor responded that most people say this and actually sleep quite well during the study. I arrived at a hospital for an in-laboratory sleep study and what followed was the worst night of my life. I couldn’t sleep, couldn’t move due to the number of zany instruments attached to my body and was quite pained by the experience. I vowed never to get another sleep study done. As a patient with severe ME who barely slept during the night- I considered the experience as torturous. My results indicated that I slept for 8 minutes during the entire night and that I had restless legs syndrome. My sleep specialist requested that I get another sleep study done as I hadn’t achieved a sufficient amount of sleep. I reluctantly agreed under the proviso that I take sleeping tablets.

My second sleep study involved about 4 hours worth of sleep (typically they require about 2 hours to get sufficient data). The results didn’t show too many abnormalities but suggested that I might have sleep apnoea but this conclusion was nebulous. I went to a new sleep specialist and they wanted me to get another sleep study done, this time testing for narcolepsy. I ended up going to a third sleep specialist who said that the two sleep studies I had undertaken were done by a dubious company who go through thousands of patients a night and the results were meaningless. He instructed me to get another sleep study done. After I initially vowed to never get a second sleep study done, I was going to undertake my third! I told the specialist that I would need to take sleep tablets and he agreed.

The sleep technician at this sleep study centre told me that per year they have around 1000 patients and 2 or 3 that they don’t get enough sleep from to get results. This highlighted to me the breadth and rarity of my sleep issues. My results from this third study said “Features consistent with Upper Airways Resistance Syndrome-like arousals. Limb movement. Sleep fragmentation from spontaneous, respiratory and limb causes.” I will discuss Upper Airways Resistance Syndrome and Restless Legs Syndrome in the next two sections.

 

Upper Airways Resistance Syndrome

Upper Airways Resistance Syndrome (UARS) is similar to sleep apnoea. UARS occurs when the upper airways narrow causing reduced airflow then subsequently deeper breathing which wakes the patient (often they are unaware of this waking). It causes unrefreshing sleep and fatigue. Treatment involves CPAP therapy through a mask that is similarly used in treating sleep apnoea, nasal steroids, good sleep hygiene, oral appliances and surgery depending on the severity. Dr. Teitelbaum writes briefly about UARS in his books however the most comprehensive guide can be found here: http://www.uarsrelief.com/uarsreliefebook.pdf

 

My Experience with Treating UARS

I tried CPAP therapy with a mask attached to my face delivering a steady supply of air into the nostrils. This treatment was troublesome as my poor sleep in tandem with the peculiar mask conspired to make it difficult for me to fall asleep and stay asleep. After a month of trying CPAP, my specialist said that it wasn’t working and that it’s quite common for patients not to tolerate this treatment. Reducing nasal congestion is another angle to treat UARS. I tried a nasal dilator called Nozovent that is essentially a small piece of plastic that expands the nasal passages. I experienced slightly more refreshing sleep for a week but this wore off. Some people use nasal strips for UARS that cover the bridge of the nose. I’ve been using these permanently for 8 years and continue to use them. I tried an antihistamine before sleep to reduce congestion yet this caused me a great amount of next-day fatigue. I also incorporated a nasal irrigation device into my daily routine to no avail. It was time to try and treat the Restless Legs Syndrome instead.

 

Restless Legs Syndrome

Restless Legs Syndrome (RLS) is a disorder often occurring whilst the patient is at rest that entails an unpleasant feeling in the legs and sometimes arms. This limb movement can result in sleep disturbance. RLS may be the result of certain medical conditions or it may be a stand-alone symptom. Iron deficiency is the cause of around 20% of RLS cases. If an RLS patient’s ferritin level is below 100ng/ml it is often recommended that they take an iron supplement despite this ferritin level being considered as normal by laboratory standards. Often in these patients the RLS will then be cured.

Several prescription drugs are sometimes used to treat RLS. Gabapentin (I’ve written more extensively about Gabapentin as an ME treatment here) may act as a calcium channel blocker. Pramipexole is another treatment, which is a dopamine agonist belonging to the non-ergoline class. Clonazepam (a benzodiazepine) which is a polarising ME treatment is another possible RLS treatment. I’ve written more about Clonazepam here. Levodopa is another drug sometimes used to treat RLS. This treatment is an amino acid that can cross the blood-brain barrier and thus can increase dopamine levels. In general, drugs used to treat Parkinson’s disease are abundantly used to treat RLS.

 

My Experience with RLS Treatments

I began taking Gabapentin several years ago and it slightly improved my sleep yet my RLS remained untouched. Its effects gradually wore off and thus I had to keep increasing the dosage. Eventually I stopped the treatment. I have tried Clonazepam on two occasions. A dosage as small as 1/8^th of a 0.5mg tablet caused me to experience next day sedation. I have tried Pramipexole however 1/8^th of a 0.25mg tablet caused me insomnia. I am simply unable to sleep and feel jittery if I take this small dosage. Over the past 3 years I have become more sensitive to medications in general.

I have been using a weighted blanket for the past few months and I believe this has reduced some of my RLS intensity although my subjective sleep quality remains just as poor. Weighted blankets are thought to work by applying deep and firm pressure on the body. One study tracked weighted blanket usage amongst insomniacs and 4 out of 5 subjects preferred the weighted blanket claiming that it made them fall asleep easier and feel more refreshed. These patients also, based on sleep testing, slept for a longer period and spent less time awake during the night. Other studies have found weighted blankets help those with ADHD sleep. Another study found that autism patients preferred the weighted blanket to their normal blanket.

 

General Sleep Tips

There are some general tips I have tried to adopt with the goal of improving my sleep and I will elaborate on these here. It is important to have a regular bedtime and stick to this time. Invest in a quality mattress. You spend a large portion of your life on a mattress so it’s worth buying a quality one. Avoid caffeine or alcohol near bed time. Try relaxation exercises before bed and whilst trying to fall asleep. Avoid blue light from electronic devices in the hours leading up to sleep. This can be achieved by either not using the devices or turning a blue light filter on in these devices (this filter already exists in some items such as iPhones) or install blue light filters. Florescent light-bulbs and LED lights are also blue light offenders. Blue light suppresses production of melatonin. According to a study, sniffing lavender oil before trying to sleep for 2 minutes at 3x 10 minute intervals results in deeper sleep and subjects feeling more vigorous in the morning.

There are some techniques that can help people fall asleep faster or go back to sleep quicker if they have woken up during the night. These include the following-

When trying to sleep, try a technique that the US military uses. This entails:

1. Relax the muscles around your face remembering to relax your jaw, tongue and area around the eyes.
2. Drop your shoulders as low as they will go followed by the upper part of your arms then the lower part of your arms.
3. Take a breath out and relax your chest then legs from the waist downwards.
4. Try to clear your mind and relax for 10 seconds then think about either:

Lying within a canoe on a still lake with a blue sky above you and water beneath your canoe.

Lying within a hammock that is in a pitch black room.

After practising these techniques for several weeks, they should become more effective.

Another technique involves the 4-7-8 breathing method.

1. Firstly place the very tip of your tongue behind your upper front teeth.
2. Exhale through your mouth whilst making a “whoosh” sound.
3. Close your mouth and inhale through your nostrils for a period of 4 seconds.
4. Hold your breath for 7 seconds.
5. Exhale through your mouth whilst making a “whoosh” sound for 8 seconds.
6. Repeat the cycle 3 more times.

A study found that insomniacs who pictured an environment that makes them feel both calm and happy (e.g. a beach or waterfall) fell asleep 20 minutes faster on average than other insomniacs.

Progressively relaxing parts of your body is a technique recommended by the National Sleep Foundation. The process involves tensing your muscles starting with your toes, for 5 seconds and then relaxing them for 30 seconds. Work your way from your toes up to your head.

 

Sleep Aids:

I have written about what many ME/CFS specialists recommend as sleep aids here. There are some other sleep aids that are available over the counter and are alternatives to prescription treatments.

 

Glycine: Some people describe glycine as a miracle sleep supplement. A protocol sometimes used is to start at 500mg and work up to a maximum dosage of 2-3 grams. Studies have shown that glycine may reduce insomnia, improve sleep quality and promote restful sleep, increase the efficiency of sleep and help make the taker fall asleep quicker. It can also lower body temperature and increase serotonin levels.

I tried this treatment last year but experienced insomnia and started to feel slightly delirious.

 

L-theanine: This supplement is an amino acid that is found in tea leaves. L-theanine increases levels of serotonin, dopamine and GABA and reduces levels of excitatory brain chemicals. Another facet of l-theanine is its ability to promote alpha brain waves. A study found that it helped improve the sleep quality of boys with ADHD. Doses used tend to be in the 100mg-400mg range. Some people have used 1-2 grams of l-theanine.

My experience with this supplement was fairly positive in terms of keeping me asleep however I eventually stopped taking l-theanine.

 

Ashwagandha: This Indian herb has been shown to modulate and lower cortisol levels and improve GABA levels. A study found that in mice, Ashwagandha improved sleep. Doses between 300mg and 600mg are sometimes used for sleep. It may also increase T4 levels.

I haven’t tried this treatment yet but plan to.

 

Oleamide: Oleamide can at higher doses improve REM sleep cycles whilst at lower doses it can cause the body to feel relaxed. It may promote GABA and produce serotonin production. Doses tend to range from 100mg-400mg with sublingual doses the most effective.

I tried this treatment but it gave me insomnia.

 

Valerian: This is one of the most widely researched supplements for sleep. It is sometimes used in tandem with hops. Studies have found that valerian can help people fall asleep quicker, improve the quality of sleep and the amount of sleep. Valerian doses for sleep typically range from 400mg-900mg.

I used this treatment for a long period of time and found it to be my most effective sleep aid supplement. It wasn’t a panacea for me and I have since stopped using it but I will start trying it again soon.

 

Melatonin: Studies have found that melatonin can improve circadian rhythm sleep disorders, delayed sleep phases, insomnia and sleep-wake cycle issues.

I take sublingual melatonin every night and my sleep is worse than normal if I miss a dose.

As always, consult a physician if you plan on trying any of the aforementioned treatments.

 

Conclusion

Currently my sleep issues are as irksome as ever from unrefreshing sleep to not enough sleep (and my ME riddled body craving sleep). I believe that my sleep problems are simply another secondary symptom stemming from my ME; indeed fulfilling ME criteria is largely contingent on the existence of sleep problems. The 3 sleep specialists I have seen seemed generally ignorant about ME/CFS. My taxi driver who drove me home from an appointment perhaps gave me the best advice, he exclaimed “You can’t be expected to sleep in a sleep study if you have all that equipment attached to you and sleep problems already!”

My Experience with Rituximab for ME

 
In a subsequent blog entry; when the phase III trial is fully released, I will detail the theory behind using Rituximab as an ME treatment as well as present the studies investigating its usage. This blog entry is focused on my experience with Rituximab.
 
I had to go through the laborious task of seeking government approval prior to starting Rituximab. This process was just as you would expect bureaucratic dealings to be. Another barrier I encountered was the extremely high cost of the drug and affording it. I was lucky enough to come 2nd in something called AFL SuperCoach for the 2017 season. It is essentially a fantasy sports game involving making inferences from Australian rules football statistics and is largely dependent on luck. This luck (or lack thereof) has been a key theme permeating my Rituximab experience. On the surface certain events would appear lucky only for the spool of bad luck to unwind. The money I luckily won from SuperCoach covered my first infusion and part of my second infusion.
 
During October 2017, I attended a cancer centre for my first infusion: 1000mg of Rituximab. I was told the infusion would take around 6 hours. I knew being away from home for this period of time would induce a terrible crash hence I took bicarb before I left which seems to slightly ward of my crashes. Upon arriving at the cancer centre I had to sign some forms at reception for a few minutes. It was here that I got a glimpse at how my ME stacked up against several cancer patients in terms of the ability to perform certain tasks. After a couple of minutes on my feet, I had to sit down. Meanwhile, several sprightly cancer patient who looked in their 80s or 90s were able to stand.
 
I was given Hydrocortisone, Phenergan and Panadol prior to the infusion. Rituximab is a heavy duty drug and these 3 drugs are aimed at lessening the side effects and improving the tolerability of Rituximab (never before had I taken drugs to prepare for another drug). The infusion starts at a deliberately measured rate to mitigate the chance of side effects. Watching the Rituximab drip into the infusion apparatus was almost hypnotic as it created miniature ripples.
 
I took regular bathroom trips and it was on one of these trips two hours into the infusion that I caught a glimpse of myself in the mirror. My neck and sides of face had begun to develop a rash. I nonchalantly informed a nurse of the rash, after considering not mentioning it. She examined the rest of my skin and across 75% of my body was a bright red rash that would best blend in amongst a Google image search of “bad rash.” The snails-paced world of the cancer infusion centre was sent into overdrive. I had around 15 nurses swarm around me, phone calls to doctors were made and I was the centre attraction of a grotesque show of sorts.
 
At this stage the infusion was only 10% complete and my thoughts flickered between “what a waste of money”, “I was really hoping Rituximab was going to cure my ME and that hope is fading” and “I hope this rash isn’t foreshadowing a nasty reaction or death.” After much commotion and discussion I was pumped full of more Hydrocortisone and Phenergan. I pleaded for the rash to go in order for me to continue the infusion. The rash faded and surprisingly I was allowed to continue the Rituximab infusion albeit at a slower rate than before. I overheard a nurse murmur “I think we’ll be here until midnight.”
 
I tolerated the rest of the infusion and after 8 hours had completed the 1000mg. Upon returning home I experienced shortness of breath which continued the next day before disappearing. Two weeks after the first infusion I returned to the cancer centre for my second and last dose of 1000mg of Rituximab. On this occasion I didn’t develop a rash although I did experience shortness of breath again. During the following few weeks I noticed a persistent tenderness on my arm, separate from the infusion sites and an increase in bowel movements.
 
The smaller Rituximab studies on ME patients presented remarkable results and the entire ME community had clung on buoyantly for the larger phase III trial. Two weeks after my second infusion, I logged on to the Phoenix Rising forums and read the clipped headline “Rituximab Phase III- Negative Result.” The timing of this was particularly cruel for me. If I had found this result out a couple of weeks earlier I wouldn’t have pursued this course of treatment. I felt like I was now waiting for Godot. It was expected the study would be revealed at some point deep into 2018. I still tried to cling to a modicum of hope.
 
Around 3 weeks after the infusion I started to develop a strange, new type of fatigue that was analogous to crashing despite not having done anything. This occurred seemingly at random around 2 days a week and resulted in me having to lie in bed unable to talk or move any great deal. I would toss my Adelaide Crows scarf outside my door as a sign to my family to not disturb me. Fatigue is a noted side effect of Rituximab, something I’m all too used to. The goalposts had now shifted. I had gone from yearning for an ME improvement from the Rituximab to now wishing that it didn’t make my ME worse. The new, extra type of fatigue lasted intermittently until 4 months after the infusion. At this time it stopped and it hasn’t re-emerged since.
 
Four months after the infusion I began to experience a spate of neurological symptoms. I developed a tremor in my hands and legs that is omnipresent. I also acquired another type of tremor; perhaps known as a postural tremor. If I raise my legs, bend my knees, raise my head and even smile then the muscle I am using begins to shake; in the case of my legs, quite violently. The symptom of mouth quivering every time I smile seems almost emblematic of my entire Rituximab experience.
 
I have also developed vision problems- a sensitivity to certain types of light. I’ve been plagued by hypnic jerks: sudden bodily shakes that occur when I’m falling asleep. I have begun to feel slightly wobbly on my feet- not severe enough for others around me to notice but a definitive symptom all the same. Whilst lying in bed, I’ve also experienced regular burning hands and red palms in tandem with a strong pulse. The former symptom is perhaps erythromelalgia whilst the later symptom occurs on different parts of my body. As a collective, most of my new symptoms seem to wax and wane in intensity. For a fortnight I might not notice them as much and for the next month they may return with a vengeance.
 
It would be foolish to definitively link this new glut of symptoms to the Rituximab. I had a brain MRI performed which was normal and fortunately for me ruled out MS and PML (a rare disease that is sometimes caused by Rituximab). I was fast-tracked to see a neurologist and bypassed the long waiting list to see one within 2 days which in itself was slightly alarming. The neurologist seemed uncertain as to what was causing my symptoms. My specialist physician is on the same page as me regarding the most likely root cause of the plethora of my new neurological symptoms. He thinks the Rituximab either directly caused my symptoms or set off some other process in my body that has resulted in the aforementioned neurological signs. The timing seems to fit. Rituximab isn’t renowned for causing neurological signs such as tremor, some 4 months after treatment (on occasions it causes them directly after infusion) yet there doesn’t seem to be a better explanation at the moment (although I am exploring an enterovirus reactivation hypothesis). I am reluctant to paint the new symptoms as ME- for starters I have only developed a couple of new ME symptoms in the past decade.
 
Overall, as I write this 9 months after my infusions, I can tolerate the new symptoms yet in a week’s time they may again increase in intensity. The Rituximab saga certainly caused some turbulence in my life and it had prevented me from trying other treatments. I have just started to dabble in some more treatments for my ME. There were certain moments across this Rituximab journey that are etched in my mind as pivotal points. For me the greatest lesson has been to not necessarily treat events as intrinsically good or bad. The ripples cast from each event spread in unlikely, unforeseen ways. In some ironic sense, learning this lesson has been the one good ripple from my Rituximab experience.

 

 

 

Mestinon for ME

Mestinon, AKA Pyridostigmine, is an acetylcholinesterase inhibitor typically used to treat myasthenia gravis- a neuromuscular disease. It is a drug that can markedly reduce fatigue and enable patients to exercise in general disorders.

 

ME Specialists and Mestinon

Pulmonologist, Dr. David Systrom, specialises in patients with disorders beneath the exercise intolerant umbrella. As cardinal symptoms of ME include post-exertional malaise and exercise intolerance, Dr. Systrom has begun to focus on this patient cohort. He has conducted invasive cardiopulmonary exercise testing on ME patients that can determine oxygen usage and blood flow abnormalities.

Over the past three years, Dr. Systrom has given Mestinon to hundreds of his exercise intolerant ME patients with autonomic nervous system anomalies. He has found that it has provided many patients with their lives back and “really helped many people.” Dr. Systrom encourages his ME patients to slowly increase their exercise levels, typically on a recumbent bike while on Mestinon. Dr. Systrom’s ME theories and rationale for using Mestinon can be found here.

An ME patient of Dr. Systrom experienced a miraculous recovery on Mestinon and her story can be found here. She gradually titrated her dosage upwards to 180mg a day, presumably taken in smaller doses e.g. 60mg three times per day.

Dr. Goldstein has included Mestinon in a list encompassing his favourite drugs for ME patients. He has noted that it has improved patients’ fatigue, cognitive impairment, muscle weakness and muscle aches. Dr. Goldstein believes that Mestinon may benefit ME patients due to the drug increasing growth hormone levels which are typically low in ME patients. His recommended dosages are in the 30mg-60mg a day range.

Dr. Teitelbaum has written briefly on Mestinon and has an interest in its ability to increase growth hormone in ME patients. He cites research by Dr. Robert Bennett that has found low growth hormone levels in ME patients. Dr. Teitelbaum also parrots Dr. Bennett’s finding that Mestinon can increase growth hormone levels when used at a dosage of 30-60mg taken 3-4 times daily. Renowned cardiologist, Dr. Blair Grubb, also has many of his POTS patients on Mestinon.

 

Studies

A Japanese case study by Kawamura et al. found that all three ME patients experienced positive “dramatic effects” from the Mestinon. The subjects had experienced ME for 3, 10 and 15 years and had dysautonomia and EBV titers. The patients responded to a daily dose of either 10mg or 30mg of Mestinon and were on the drug for one month. The authors concluded by strongly recommending small doses of oral Mestinon (10mg per day) in ME patients with:

• Mild impairment of autonomic functions.
• A positive EBV test (anti-VCA IgG).
• An increase (40% plus) in response to the repetitive nerve stimulation test.

A Fibromyalgia study by Jones et al. found that patients experienced a significant improvement in sleep and anxiety after taking Mestinon. 154 out of the 165 Fibromyalgia patients completed the study with the authors theorising that the Mestinon helped due to improving vagal tone and therefore sleep and anxiety.

A study by Kanjwal et al. examining Mestinon usage on POTS patients found that 168 out of the 203 subjects were able to tolerate the drug. 55% experienced a reduction in fatigue after taking the treatment. 51% of those who tolerated the Mestinon experienced an improvement in orthostatic intolerance.

A study by Arvat et al. found that 60mg of Mestinon causes an increase in growth hormone. A study by Berwaerts et al. found that ME patients tended to have reduced nocturnal secretions of growth hormone. At one stage, Dr. Cheney believed low growth hormone was instrumental in the pathogenesis of ME. His musings about this can be found here.

Potential Mechanisms of Action in ME Patients

Mestinon may benefit ME patients due to:

• Increasing oxygen and blood flow to the muscles’ mitochondria.
• Increasing growth hormone levels.
• Improving parasympathetic nervous system and vagus nerve functioning.
• Increasing acetylcholine and thus promoting REM sleep, improving muscle movements and enhancing cognitive faculties.
• Raising exercise tolerance.

 

My Experience with Mestinon

My planned Mestinon dosing schedule involved an initial dose of 15mg and if tolerated, a gradual increase to 15mg taken 4 times a day. If I didn’t reap any benefits at this dose, I planned to venture up to 60mg taken 3 times per day (180mg per day total). I began a 15mg dose of Mestinon on the afternoon of the 1^st of September. What followed was quite extreme sleepiness and drowsiness for the next 7 hours until I went to sleep at my normal bedtime.

The next day I trialled 15mg of Mestinon taken just before bedtime with the hope that this Mestinon-induced drowsiness would improve my sleep. Unfortunately my sleep was worse than normal! I would continuously wake just before my normal waking time. I also experienced more severe restless legs syndrome during this period. Another downside of the Mestinon was the next day sleepiness I would still inevitably endure. After a week of taking the 15mg dose of Mestinon before bedtime that was inducing continual poor sleep and RLS, I decided to cease the medication.

Dosage and Side Effects

In myasthenia gravis, the dosage of Mestinon is typically in the ballpark of 180mg a day (often taken in several smaller dosages). ME patients have generally used much lower doses, generally 30mg a day, although some patients have ventured up to 180mg a day. The Kawamura et al. case study on ME patients taking Mestinon recommended 10mg a day. In contrast, Dr. Systrom seems to encourage patients to gradually increase the dosage to 180mg a day if lower doses are tolerated. Dr. Goldstein is more moderate in his approach, recommending ME patients take 30-60mg per day.

Dr. Systrom states that any side effects are generally minor and may include diarrhea, gastrointestinal issues or twitching muscles. Anecdotally online, some ME patients have reported side effects that are typically gastrointestinal and transient. The Kanjwal et al. POTS study found the most common side effects to be gastrointestinal in nature with 19% experiencing this symptom. The Jones et al. Fibromyalgia study found that Mestinon was generally well tolerated. Mestinon should be used with caution in patients with diabetes or asthma.

 

Conclusion

Due to the side effects of sleepiness and also ironically, poor sleep, I only managed to take a low dosage of Mestinon for one week. It is therefore difficult to ascertain if it would have evoked any positive effects if taken longer and at a higher dose. The patients that may benefit most from Mestinon are; exercise intolerant patients with autonomic nervous system anomalies, patients with low levels of growth hormone, those with POTS or those with EBV and an increase in response to the nerve stimulation test. Mestinon is generally well tolerated with gastrointestinal side effects the most likely. Anecdotally online, there are a reasonable number of patients who have taken Mestinon, with some calling it a “miracle drug” for them, on the flip side, others have reported no effect or side effects.

Galantamine and Ibudilast for ME

This blog entry will examine the rationale behind Galantamine and Ibudilast as treatments for ME both individually and in conjunction. I will also detail my experience with this treatment synthesis.
 

Galantamine

Galantamine belongs to a class of drugs known as ‘cholinesterase inhibitors.’ It is most commonly used in the treatment of Alzheimer’s disease as well as other indications involving circulation based memory impairment. Galantamine is unique as it is available as both a supplement readily accessible online as well as a prescription drug. There are a glut of possible mechanisms by which it may benefit ME patients.
 

Galantamine’s Mechanism of Action

Galantamine may benefit ME patients due to:

• Increasing acetylcholine
• Reducing DHEAS levels
• Normalising the DHEAS/cortisol ratio
• Reducing bodily inflammation
• Lowering mast cells release
• Supressing microglial activation (Microglial cells are essentially immune system cells in the brain that when overactive can cause various symptoms.)

 
ME patients responding to Galantamine most commonly note an improvement in sleep quality and length, an alleviation of cognitive impairment, a reduction in pain and dissipation of fatigue.
 

 

Studies of ME/CFS Patients Taking Galantamine

The First study examining the efficacy of Galantamine on ME/CFS patients was by Snorrason et al. in 1996. The study authors postulated that a ‘cholinergic deficit’ may be responsible for ME/CFS symptoms. As Galantamine can increase acetylcholine, the authors explored whether ME/CFS patients would improve as a result of this treatment. 49 ME/CFS patients began the study and 39 finished the Galantamine protocol. 43% of these patients reported at least a 50% improvement in the areas of ‘fatigue, pain and sleep.’ This was in contrast to just 10% of the placebo group noting an equivalent improvement. The study mentions that when symptoms did dissipate, it occurred gradually and was classified as significant only 4-8 weeks into treatment. The patients who did improve by greater than 50% didn’t relapse despite stopping the Galantamine. The major symptomatic improvement in this study centred on sleep. 60% of the ME/CFS patients taking Galantamine had a 70% of more improvement in sleep.
 
The second study was performed by Blacker et al. in 2004. This study featured 352 CFS patients taking varying amounts of Galantamine from 2.5mg to 10mg. 82 patients taking a placebo were also involved in this study. The broad Fukuda criteria were used to select ‘CFS patients.’ After 16 weeks of treatment, the CFS patients in this study failed to improve relative to the placebo group. The lack of effect from this study may have been due to the dubious CFS criteria used, the low dosage of Galantamine or indeed the lack of efficacy of the Galantamine.
 
The final Galantamine-ME/CFS study was by Turan et al. in 2009. The authors noted that many CFS symptoms such as; cognitive impairment, sleep problems, mental fatigue and HPA axis dysfunction are indicative of a ‘cholinergic deficit.’ This study focused on stress hormones such as DHEA and cortisol and their alterations in CFS patients taking Galantamine. The study contained 29 CFS patients, who were diagnosed with the Fukuda criteria as well as 20 healthy controls. The CFS patients were given 8mg of Galantamine per day for 4 weeks.
 
The patients who responded to Galantamine treatment had significantly higher pre-treatment DHEAS levels (1744ng/ml on average) and significantly higher DHEAS/cortisol ratios (146 on average). The CFS patients who didn’t respond had DHEAS levels (1122ng/ml on average) and DHEAS/cortisol ratios (128 on average)- both at similar levels to the healthy controls. After treatment with Galantamine, the CFS responders DHEAS levels dropped from 1744ng/ml to 1164ng/ml on average. The DHEAS/cortisol ratio of the CFS responders went from 146 to 121 on average. Turan et al. concluded that the various stress hormones normalising with Galantamine treatment indicated that a ‘cholinergic deficit’ may be central to CFS.
 

Side Effects

The most common side effects from Galantamine are nausea and headaches. Other frequently noted symptoms mentioned in the ME/CFS studies include; vomiting, sweating, diarrhea, confusion and hallucinations. The Blacker et al. study noted that 22.6% of ME/CFS patients taking the Galantamine withdrew from the study, although 15% of patients in the placebo group also withdrew. Unsurprisingly, this study also found that the frequency of side effects increased as the dose of Galantamine was raised. The Snorrason et al. study listed nausea as the most common side effect although stipulated that this was “dose-dependent and reversible.” The authors also stated that some patients at the lowest dosage of 5mg developed nausea. Snorrason et al. recommend that ME patients begin Galantamine treatment at very low doses and are monitored by a physician. Some non-ME users of Galantamine use this substance for its vivid dreams, although ME patients are warned not to take it close to bedtime due to the risk of it invoking nightmares.
 

Dosage

There is quite some discrepancy regarding an appropriate dosage of Galantamine in ME patients. Some patients have experienced side effects at the low amount of 2.5mg per day. As with most ME treatments, it is problematic in trying to determine a universal dose. Some patients have trialled a maximum of 4mg taken twice a day (8mg a day total) while other have ventured up to 7mg taken twice a day (14mg a day total). The ME/CFS studies used doses from 2.5mg-10mg per day. It is imperative that if a patient trials this treatment, the baseline dosage is very low and it is gradually increased if no side effects emerge.
 
Some countries class Galantamine as a supplement while other counties categorise it as a drug. It is widely available online in various formulations, some containing choline or another substance that may enhance its efficacy. Some takers of Galantamine buy choline separately to add to its effectiveness. Galantamine should be taken with food. An alternative treatment is royal jelly- a product that may be better tolerated that Galantamine and also contains acetylcholine.
 

 
 

Ibudilast

Ibudilast is a Japanese drug that has traditionally been used as a treatment for asthma and stroke. It has more recently been prescribed, with some success, to patients with multiple sclerosis and those with amphetamine, opioid or alcohol addictions.
 

Mechanism of Action

Ibudilast may benefit ME patients due to:

• Preventing the creation of inflammatory cytokines
• Inducing pro-inflammatory molecules
• Reducing neuropathic pain
• Being neuroprotective
• Reducing brain inflammation
• Stopping microglial cell activation
• Lowering the production of nitric oxide

 

Ibudilast Studies

While Ibudilast is yet to be studied on an ME patient population, several studies of relevancy have been performed. The following studies were performed on human subjects, as opposed to in vitro.
 
In progressive multiple sclerosis patients, Ibudilast has been found to have an effect on preserving brain volume as well as slowing disability progression. Trials are continuing to investigate the usefulness of Ibudilast as an MS treatment.
 
A 2016 study by Cooper et al. found Ibudilast to be a useful glial modulator and hence a treatment for opioid withdrawal.
 
A 2008 study by Inoue et al. examined the usefulness of Ibudilast in increasing blood flow in the brains of patients with cerebrovascular disease. The subjects noted a reduction in dizziness and depression. Objectively, the patients had an increase in their blood flow in the brain, specifically in the right frontal and occipital cortices.
 
A 1993 study by Fukuyama et al. examined Ibudilast’s effects on blood flow in the brains’ of stroke patients. A large initial dose of Ibudilast led to a “remarkable increase” in blood flow around the brain when measured after 30 minutes.
 
Another 1993 study, this time by Sugiyama et al. labelled Ibudilast as a ‘cerebral vasodilator.’ The authors determined that Ibudilast caused “significant changes” in the blood flow around the brain to the affected brain areas, as measured by a SPECT scan.
 

ME Etiology Theories and Ibudilast

Dr. VanElzakker wrote a 2013 paper exploring the hypothesis that infection of the vagus nerve may cause ME. He has proposed the theory that this infection of the vagus nerve subsequently activates the microglia and hence results in ME symptoms. Within the paper, Dr. VanElzakker explains that Ibudilast may be an appropriate treatment due to it being a glial inhibitor and he writes that Ibudilast has several possible mechanisms in which it may benefit ME patients.
 
Stringer et al. did a 2013 study that found Leptin levels correlating to fatigue severity in 6 ME patients throughout the 25 days of the study. Leptin is a hormone that is created by fat cells. Dr. Jarred Younger was a part of the Stringer et al. study team and has written extensively about the potential effects that Leptin has on the body in ME patients. One of his theories involves leptin lowering the threshold of the microglia hence causing ME symptoms. Similarly to Dr. VanElzakker, Dr. Younger reportedly has an interest in Ibudilast as an ME treatment.
 
Another researcher has queried weather Ibudilast will actually target the specific type of glia that is of interest to ME patients, as there are many different types of glial cells.
 
Ibudilast is overflowing with potential as a future more widespread ME treatment. As this drug becomes more researched by scientists outside of Japan for other indications, the broad nature of this treatment has become apparent. Currently, Ibudilast is being fast-tracked through FDA trials for other conditions. Future studies on ME patients would be interesting as multiple mechanisms of this treatment would be appropriate to treat many of the etiologies proposed for ME.
 

 

Side Effects and Dosage

Ibudilast is generally void of serious side effects at the therapeutic doses used. Its use in treating asthma in Japan is testament to this. The most frequent side effect in studies have been gastrointestinal, including; nausea, diarrhea and indigestion- Although the prevalence of these have been low. In a 2 year study of Ibudilast usage, patients took either 10mg three times per day or 20mg three times per day. Gastrointestinal side effects occurred in the 30mg a day group at a rate of 11.6% and at 15.2% in the 60mg per day group. In contrast, 7.8% of the placebo group felt gastrointestinal symptoms. Tolerance to these side effects built up within 2-4 days, hence it seems to be fairly rare for a patient to discontinue Ibudilast due to side effects. Hypertension is possible due to its vasodilatory properties and it may have an antiplatelet effect hence be wary if combining Ibudilast with aspirin or anticoagulants.
 
An appropriate dosage of Ibudilast for ME patients in difficult to determine. Some non-ME patients who have the goal of improving mental acuity take it at 10mg twice a day (20mg a day total) which is the same dose that asthma patients take. Studies with multiple sclerosis patients have involved dosages ranging from 30mg twice a day (60mg a day total) to 50mg twice a day (100mg a day total). This later total of 100mg a day has been referred to in a separate study as in the “high” dosage range.
 
Ibudilast is a prescription drug that is commonly used in Japan and much of the western world is only now beginning to study and embrace it. For this reason, it is currently not available in most countries. Some ME patient and non-ME patients seeking its mental acuity effects have ordered it online without a prescription. It can be moderately expensive when used at therapeutic dosages.
 
 

Galantamine and Ibudilast

When combined, Galantamine and Ibudilast may have an increased efficacy and may work in tandem to reduce cognitive impairment. Galantamine may trigger the ‘cholinergic pathway’ and Ibudilast has the potential to lower the microglial cell stimulation. Overall, Galantamine essentially targets stopping the bodily inflammation and Ibudilast focuses on eliminating the brain inflammation. Cognitive impairment is therefore potentially being treated.
 

My Experience with Galantamine and Ibudilast

On the 4^th of November 2016, I took my first dose of Galantamine at 4mg. I began to feel dizzy for the next several hours. After several days, I increased the dosage to 6mg. I then decided to add Ibudilast into the mix and commenced with a 10mg dosage. After a few days, I increased my Ibudilast dose to 10mg twice a day (20mg a day total). While on this treatment combination, I noticed a few side effects. My sleep at night seemed more disturbed than usual and I was feeling drowsier during the daytime hours. As these side effects are sometimes linked to Galantamine, I stopped this treatment and the side effects vanished. I continued taking Ibudilast for one month at 20mg a day. I didn’t notice any distinct positive or negative effects from the Ibudilast.
 

Conclusion

The Galantamine and Ibudilast treatment synthesis is experimental. If a patient does trial one or both of these treatments, it is imperative that they are monitored by a physician. Galantamine usage in ME patients has produced mixed results in studies. In isolation, it seems most likely to benefit those patients with high DHEAS levels or high DHEAS/cortisol ratios. Side effects from Galantamine seem to occur quite frequently although for the most part aren’t serious and involve transient nausea and headaches. In contrast, Ibudilast hasn’t been studied in ME patients and it is virtually untried amongst the ME patient population. It has many possible mechanisms of action in ME patients and does look like a promising drug on the horizon. Its good safety profile also enhances its allure. In the future, I plan to trial Ibudilast, on its own, at a higher dosage and hopefully reap some of its positive effects.

Clostridium Butyricum and an Update on my ME

This blog entry will detail the theory behind Clostridium Butyricum as an ME treatment as well as my experience with this probiotic. Following this, I will examine a post-exertional malaise treatment that has proven useful to me. Finally, I will scrutinise the meaning of an abnormal blood test that I recently had.
 

Clostridium Butyricum (Miyarisan)

Clostridium Butyricum (CB) is a probiotic that many ME patients have trialled, some noting a reduction in symptoms. This treatment du jour has a 60 page thread devoted to it on Phoenix Rising that can be found here.
 
CB may benefit ME patients due to many possible mechanisms including:

• Reducing harmful bacteria and increasing levels of lactobacilli and bifidobacteria.
• Shifting the immune system from Th2 to Th1.
• Regulating the immune system of the gut.
• Increasing IgA, IgG and IgM levels.
• Lowering lactate.
• Fighting irritable bowel syndrome symptoms.
• Reducing cognitive impairment and acting as a neuroprotector.
• Minimising allergies.

 
CB can also raise butyrate levels in the body which may help ME patients due to butyrate’s mitochondrial effects. Butyrate also has the potential to create T-cells in the digestive system and hence lower patients’ gut-related symptoms. It may also lessen inflammation levels and improve patients’ immune systems. Studies have found that butyrate may reduce Crohn’s disease and ulcerative colitis symptoms. Butyrate can also be taken directly in its own distinct formulation.
 

 
Anecdotally, ME patients online who have trilled CB and benefited, have reported an enhancement in sleep quality and length, a reduction in cognitive impairment, an improvement in digestive symptoms and a general lessening of their ME symptoms.
 
CB is available at a relatively cheap price online in a formulation containing 630 miniscule-sized tablets. The recommended upper dosage according to the company that produces CB is 6 tablets taken 3 times a day (18 tablets a day total which is equivalent to 180mg). It is imperative that ME patients trialling CB begin at a much lower dosage such as 1 tablet a day and gradually increase this to a dose they feel comfortable with. Numerous patients have commented online that transient symptoms have emerged if they increase the dosage too briskly. A ‘strong’ variant of CB is also available that contains 270mg of CB within 9 tablets.
 
My experience with Clostridium Butyricum

The one realm of ME symptoms that I have largely not developed has been the gastrointestinally natured. Despite this, treatments such as probiotics often act holistically and sometimes benefit patients without many gastrointestinal symptoms. With the caveat that I’m not necessarily the target patient for this treatment, I began at a low dosage on the 19^th of December 2016. I didn’t notice any side effects and gradually increased this treatment to the maximum of 18 tablets a day. After 5 weeks of this treatment, I am yet to experience any positive or negative effects. As CB has the potential to reduce lactate, it is possible that it is working on delaying my post-exertional malaise.
 
 

A Post-Exertional Malaise Treatment

I have recently found that sodium bicarbonate (aka baking soda) wards off my post-exertional malaise. I take ¼ to ½ a teaspoon just prior to doing an unavoidable activity that would normally induce a crash. I have so far taken sodium bicarbonate on 6 occasions immediately before tasks such as going to the doctors. In the past, a crash was inevitable however as a result of this treatment, I am yet to crash. The sodium bicarbonate’s mechanism of action may involve causing a reduction of the lactate in my body. Some studies have indicated that this is a property of sodium bicarbonate and that muscles recover faster with this treatment. It is nebulous whether another aspect of sodium bicarbonate is responsible for its effects on me. Several other ME patients have noted a similar effect from this treatment.
 

 
Hip on Health Rising has written about similar treatments that when taken before exertion, may ward off post-exertional malaise. These include

• Branched-chain amino acids (5 grams)
• Catalase (600mg post exercise)
• Citrulline (1 gram)
• Coq10 (800mg)
• Creatine hydrochloride (2 grams)
• D-ribose (5 grams taken three times a day)

 
Hip’s article specifies the rationale behind each ‘crash buster’ including anecdotal reports and studies of possible mechanisms of action. The article is worth reading and can be found here.
 
I am yet to fully explore the scope of the sodium bicarbonate’s benefits and to date will still feel ‘worn out’ after a basic activity however haven’t yet experienced the dreaded crash since taking this new treatment. I also plan to trial some of the other aforementioned ‘pre-activity’ treatments and have creatine hydrochloride lined up to take next. As Clostridium Butyricum can potentially reduce lactate, I should document that my bicarbonate soda experiment did predate my taking of CB by 2 months. I should also note that sodium bicarbonate does have some side effects and hence I have only used it sparingly. I’ve written more extensively about other post-exertional malaise treatments here.
 
 

Immunoglobulin Blood Tests

I recently had a blood test that showed several abnormalities. The test was for immunoglobulins and their subclasses. I was deficient in:

• IgG
• IgM
• IgG subclass 1
• IgG subclass 2

 
An IgG deficiency is an immunological deficiency and correlates with a patient being more likely to get infections. ME patients are most likely to be deficient in IgG subclasses 1 and 3. Read et al. found an IgG subclass 1 deficiency in patients with ME/CFS. Wakefield et al. found that ME/CFS patients had significantly lower levels of IgG subclasses 1,2 and 3 compared to controls. Several other studies have also found IgG subclass deficiencies in ME/CFS patients.
 

 
Some ME/CFS patients (with or without IgG deficiencies) are treated with intravenous immunoglobulins or immunoglobulin injections. A few studies have shown that these treatments benefit ME/CFS patients, while other studies haven’t noticed any effect. Intravenous immunoglobulin treatment is of interest to me however in Australia there seems to be strict regulations on its usage hence it would be difficult for me to trial.

 

 

Treatments for ME/CFS

The following list of potential ME/CFS treatments is divided into two sections. The top part describes treatments requiring a prescription while the lower section lists over-the-counter formulations that are readily available. I have written about the majority of the following treatments elsewhere on my blog, often in more detail. Clicking on the name of the treatment will open up a new window with this information. The below, alphabetically ordered two lists, detail a brief rationale as to why each treatment may be beneficial to ME/CFS patients. I also examine the safety profile and common dosages used for each treatment. As always, consult with your physician before commencing any treatment.

 

Prescription Treatments for ME/CFS

 
Azithromycin– Azithromycin is an antibiotic that has antiviral and immunomodulatory properties. It may be effective against a broad range of bacteria, many of which have been linked to ME/CFS. A study found that 58 out of 99 ME/CFS patients had a decrease in symptoms while taking Azithromycin. Dr. De Meirleir and Dr. Nicholson are both advocates of this antibiotic and have used it on ME/CFS patients with some success.
 
Azithromycin is generally fairly low in side effects although sometimes causing stomach upset. It is normally taken 3 times a day (away from food) at a dosage of 500mg on each occasion.
 
 
Dr. Brewer’s Protocol– This protocol involves patients taking either a nasal version of Amphotericin B or a compounded Nystatin that has to be atomised. Patients should also take a chelating PX. A pilot study by Dr. Brewer found that 56 out of 151 ME/CFS patients could not tolerate the Amphotericin B. 88 out of the remaining 94 patients (93.6%) had a reduction in symptoms. Approximately a third of these 88 CFS patients reached remission. Since this pilot study, Dr. Brewer has used a compounded and atomised Nystatin due to it being safer than the nasal Amphotericin B. The theory behind Dr. Brewer’s Protocol involves treating the sinus reservoirs of mycotoxins that may be causing ME/CFS symptoms.
 
Since replacing Amphotericin B with Nystatin, Dr. Brewer’s Protocol has become safer for patients, with followers of the protocol rarely reporting nasal side effects. Patients experiencing die-off symptoms range from 30-40% according to Dr. Brewer. The appropriate dosages of the compounded and atomised Nystatin and the chelating PX are provided by the compounding pharmacy.
 
 
Clonazepam– This treatment is one of the most polarising ME/CFS treatments in existence. Clonazepam may benefit patients due to reducing the overstimulation of the brain and central nervous system. It also has potential effects as a sleep aid, neuroprotector and energy enhancer. Several ME/CFS specialists are advocates of Clonazepam under the right circumstances, such as Dr. Cheney. There are also many online reports of patients benefiting from Clonazepam.
 
The dark-side of Clonazepam involves countless ME/CFS patients’ online anecdotes stating that this drug has been the worst treatment they have ever tried as it has caused long term side effects. A dosage around the 0.5mg- 1mg range is normally used on ME/CFS patients for sleep which is a lower amount than for other conditions. An even tinier dose is recommended by Dr. Cheney if the drug is used during the day with the motive of increasing the patient’s energy. Clonazepam shouldn’t be stopped suddenly and patients should gradually reduce the dose before ceasing treatment. The common side effects of Clonazepam include drowsiness and confusion. Some ME/CFS patients have reported other side effects such as a general worsening of their condition. As Clonazepam usage can be habit forming, patients often feel like they need to increase the dose to maintain efficacy which can be a dangerous process.
 
 
Dexedrine– Dexedrine may benefit ME/CFS patients due to alleviating cognitive impairment, reducing fatigue and increasing energy. A small study found 9 out of 10 ME/CFS patients had reduced fatigue after taking Dexedrine in comparison to 4 out of 10 patients in the placebo group. Dr. Teitelbaum is a supporter of this treatment, believing that it increases energy and blood pressure. Dr. Goldstein has written that 1/3^rd of ME/CFS patients will improve as a result of taking stimulants and he has recommended amphetamine salts.
 
One of the risks of Dexedrine is that prolonged usage may lead to addiction. Dr. Goldstein has warned that if specific neurotransmitters are low in an ME/CFS patient, stimulants may increase ME/CFS symptoms. Dr. Rowe has recommended that ME/CFS patients begin with a 5mg dosage in the morning and if no improvement is noted, the dosage be increased to 10-15mg. Some patients may find that 5mg is too high for them to tolerate.
 
 
DHEA– DHEA is a hormone produced by the adrenal glands. A study found that the majority of the Japanese ME/CFS subjects had DHEA deficiency. Several studies have found the use of oral DHEA and intravenous vitamin C to be useful in treating ME/CFS.  Another study found normal DHEA levels in ME/CFS patients but low blood levels of a hormone that causes the adrenal glands to release DHEA.
 
Dr. Cheney has found that DHEA is more effective in less severe cases of ME/CFS and that sometime symptoms may worsen if severely ill patients take this treatment. Dr. Myhill recommends Pregnenolone as an alternative to DHEA. Some doctors have experienced success in prescribing lower doses of DHEA such as doses less than 10mg. Another ME/CFS specialist recommends 50mg every second day. Palpitations, hair loss, acne and an upset stomach are some possible side effects.
 
 
Fludrocortisone– Fludrocortisone is a synthetically produced hormone. It may benefit ME/CFS patients with; hypotension, POTS, orthostatic intolerance or adrenal insufficiency. Its mechanism of action in ME/CFS patients could be due to; increasing blood volume, raising blood pressure and helping blood reach the bodies extremities. Three studies have been performed on ME/CFS patients taking Fludrocortisone with the ME/CFS patients’ level of improvement no better than the placebo group. According to Dr. Bell, Fludrocortisone is more likely to work on younger patients who are still somewhat active. Dr. Bell tries this treatment on almost all of his patients and says that it works well in approximately 25% of cases. If the drug doesn’t increase the ME/CFS patients’ activity levels by at least 50%, he stops the drug. Dr. Cheney believes that liquorice can have the same effect on patients as Fludrocortisone.
 
Many ME/CFS specialist recommend that Fludrocortisone dosages start at a very low amount such as a quarter of a 0.1mg tablet. Dr Rowe begins patients on a quarter of a tablet and if no side effects are noted, gradually increased this amount every 4-7 days to maximum of 2 tablets (0.2mg). Potassium and plenty of water should be used concurrently with this treatment. High blood pressure and depression are two possible side effects.
 
 
Gabapentin (Neurontin)– Gabapentin is a anticonvulsant drug that may benefit ME/CFS patients due to reducing pain, increasing energy and improving sleep. Its mechanism of action may be its ability as a calcium channel blocker to reduce the excretion of certain neurotransmitters that cause pain and stimulate the brain. Anecdotally, a number of ME/CFS patients have gained extra energy as a result of taking Gabapentin however in some of these cases the extra energy has worn off. Dr. Goldstein lists Gabapentin amongst his five most favoured treatments for ME/CFS. Dr. Teitelbaum uses Gabapentin for its sleep effects and Dr. Enlander uses it for stopping the ‘abnormal impulses’ in ME/CFS patients’ brains. Three studies have found Gabapentin to be beneficial to Fibromyalgia patients in the areas of sleep enhancement and pain reduction.
 
Gabapentin is considered to be fairly safe with a Cochrane review finding that serious adverse effects were no more common in the Gabapentin group than the placebo group. Dizziness, somnolence, peripheral oedema and gait disturbance are the most common side effects. Dosages should begin at low levels and only be increased if tolerated. ME/CFS specialists tend to start patients at 100mg-800mg and if no side effects occur, the dose is gradually increased up to 2400mg-5000mg. These doses are the total daily dosages and should be split up into three dosages across the day.
 
 
Heparin– Heparin is an anti-coagulant drug that may benefit ME/CFS patients who have hypercoagulation. A Heparin-ME/CFS study found all 9 patients gaining improvement with 5 noting significant improvement. Another paper refers to 60 ME/CFS/Fibromyalgia patients taking Heparin with an average improvement of 85%. Dr. Teitelbaum writes that Heparin helps about 50% of ME/CFS patients who haven’t benefited from any other treatment. It is imperative that ME/CFS patients have coagulation testing performed to determine Heparin suitability before commencing treatment.
 
Depending on what type of Heparin is used and what delivery method is chosen, the possible side effects of Heparin vary. If unfractionated Heparin is injected subcutaneously, regular blood tests to monitor treatment are a necessity. Heparin-induced thrombocytopenia is a potential side effect with this treatment although with Low Molecular Weight Heparin this is less likely to occur. A DEXA bone density test and liver and kidney function tests may be required before starting Heparin treatment. Sublingual Heparin and Low Molecular Weight Heparin are considered safer than unfractionated Heparin. Dr. Teitelbaum recommends those patients taking unfractionated Heparin start with 5000 unit injections twice a day and if blood tests are normal, the dose be gradually increased to a maximum of 8000 units twice a day.
 
 
Isoprinosine (Immunovir)– Isoprinosine may benefit ME/CFS patients due to its effects as an antiviral as well as its various immunomodulatory properties. A study found that 6 out of 10 ME/CFS patients benefited by taking Isoprinosine. In those patients who improved, their CD4+, T-cells and natural killer cells dramatically increased. Dr. Sharp believes Isoprinosine is one of the most helpful, safest and cost effective drugs for ME/CFS patients.
 
Isoprinosone may increase uric acid levels and therefore shouldn’t be used by those with gout. ME/CFS specialists generally pulse the dosage of Isoprinosine so patients don’t develop a tolerance to the drug.
 
 
Low Dose Naltrexone (LDN)– When used at low doses, Naltrexone causes the body to create more opioids which in turn may; relax the microglial cells, block pain, create endorphins and modulate the immune system. A small, pilot study on Fibromyalgia patients found that subjects experienced on average a 30% decrease in pain and fatigue while taking LDN. A second placebo controlled study on Fibromyalgia patients resulted in 32% of those taking LDN experiencing a significant reduction in pain as well as either a significant reduction in sleep problems or significant reduction in fatigue. Dr. Bihari reports that approximately 50% of ME/CFS patients are helped by LDN. Stories litter the internet of ME/CFS patients benefiting from this treatment.
 
LDN is considered one of the safest treatments for ME/CFS with few patients experiencing side effects. The most common side effect is sleep disturbance. The dosage used is normally in the 1.5mg-4.5mg range. LDN is generally taken at night before falling asleep.
 
 
Magnesium Injections– A study found low red blood cell magnesium levels in ME/CFS patients. After intramuscular magnesium sulphate injections, 12 out of the 15 ME/CFS patients improved compared to 3 out 17 patients receiving the placebo improving. A study determined that despite normal magnesium blood levels, Fibromyalgia patients had low intracellular levels of magnesium. Dr. Myhill has found approximately 70% of her ME/CFS patients improving after receiving magnesium injections.
 
Magnesium injections can cause temporary pain at the injection sight. High doses may cause diarrhea. Intramuscular injections are generally given once or twice a week.
 
 
Melatonin– Melatonin is a hormone whose primary role as an ME/CFS treatment is to aid sleep. One study found that it improved ME/CFS patients’ ability to function and that it enhanced patients’ quality of life. Another study concluded that it reduced patients’ fatigue levels. Dr. Wright states that over 60% of his ME/CFS patients produce undetectable levels of Melatonin. As well as improving quality of sleep, this treatment may be beneficial due to its anti-inflammatory and antioxidant effects.
 
The most common side effects of Melatonin are morning drowsiness and headaches. These side effects may dissipate if the dose is decreased. Melatonin is listed in this section under the ‘prescription treatments’ umbrella due to a prescription being required to gain it in Australia despite formulations with negligible amounts of Melatonin being available over the counter. Other countries may have differing laws regarding prescription requirements to gain Melatonin. Some doctors use doses as low as 0.5mg while most doctors recommend doses in the 3-9mg range. It is normally taken at night, before sleep.
 
 
Myers’ Cocktail– The Myers’ Cocktail is an intravenously administered mixture of supplements including; magnesium, calcium, vitamin C, B vitamins and sometimes further ingredients. A study on Fibromyalgia patients receiving this treatment found that most of the subjects noted improvements however the placebo group that received a saline solution also improved. Intravenous saline solution is considered by some to be an effective treatment for ME/CFS/Fibromyalgia hence it is conceivable that both groups did improve. The authors noted that both groups experienced “strong symptomatic relief.” Dr. Teitelbaum is an advocate of Myers’ Cocktails and believes they can provide ME/CFS patients with more energy. Dr. Majid Ali had found that 15 grams of intravenous vitamin C (an ingredient in Myers’ cocktails) can fix the abnormal shapes of ME/CFS patients’ blood cells and hence improve blood flow.
 
Some patients feel sleepy immediately after a Myers’ cocktail for a short period of time. If the patient feels excessive warmth, dizziness, nausea or a headache during the Myers’ cocktail IV, they should notify the physician. The dosages of the individual ingredients within a Myers’ cocktail vary and are at the physician’s discretion.
 
 
Nexavir (Kutapressin)– Nexavir is a porcine liver extract that is administered via subcutaneous or intramuscular injection. Studies have found that Nexavir can inhibit EBV in vitro and HHV-6 replication in vitro by greater than 90%. A study of 270 ME/CFS subjects found that a staggering 96% of patients receiving more than 40 Kutapressin injections reached remission or near remission status. 71% of patients receiving 11-40 injections obtained remission or near remission levels. If an ME/CFS patient had high EBV-EA-IgG titres, they were more likely to improve in this study. A final Kutapressin study contained 130 ME/CFS patients with 85% noting significant improvements. 43% of patients reached remission while a further 42% of patients gained near remission status (they had a few residual symptoms). Dr. De Meirleir had found 67% of his ME/CFS patients responding to Nexavir in comparison to 17% receiving the placebo improving. Dr. Cheney, Dr. Enlander, Dr. Teitelbaum and Dr. Lapp have all been advocates of Nexavir or an analogous version of Nexavir.
 
Out of the 400 patients across both Kutapressin- ME/CFS studies, only 1 person experienced new symptoms and a deterioration of function following Kutapressin injections. Some physicians are reluctant to prescribe antivirals including Valtrex or Famvir due to side effects and therefore prescribe Nexavir as a safer alternative. Nexavir is contraindicated in those allergic to pork or liver products. It shouldn’t be used by those taking MAO inhibitors. The most common dosage is 2mls administered daily although some patients start with a lower dose.
 
 
Nimodipine– Nimodipine is a calcium channel blocker that is used to improve cognitive function or reduce pain in other illnesses. Dr. Goldstein found that Nimodipine improved ME/CFS patients’ cerebral blood flow (monitored through SPECT scans) and indeed this is the treatment’s primary usage in ME/CFS patients. Dr. Goldstein has labelled Nimodipine as one of the most useful treatments for both ME/CFS and Fibromyalgia. Dr. Mason Brown has found that Nimodipine helps 20% of ME/CFS patient quickly, another 20% over 6 months and the remaining patients to varying degrees. A report on Nimodipine usage in ME/CFS patients found that 9 out of 13 experienced enhanced mental clarity or improved general functioning.
 
Possible side effects of Nimodipine include; hypotension, nausea, headache, bradycardia, skin rash and peripheral edema. Specialists generally recommend starting at a low dose (some patients begin with as little as 1/16^th of a tablet). The maximum dose normally recommended for ME/CFS patients is 30-60mg taken 2-3 times a day.
 
 
Oxytocin– This treatment is a neurotransmitter hormone whose most effective delivery method is widely considered to be injection, followed by nasal spray and finally tablets. The ME/CFS patients most likely to respond to Oxytocin are those with cold extremities. Dr. Flechas states that many ME/CFS symptoms are similar to those that an Oxytocin deficiency would cause. Dr. Goldstein found approximately 20% of his patients benefiting from Oxytocin injections and in those patients who do benefit, the improvement is dramatic. As well as Dr. Goldstein, the ME/CFS specialists; Dr. Lapp, Dr. Flechas and Dr. Teitelbaum all use Oxytocin injections on their ME/CFS patients.
 
Possible side effects of Oxytocin include; headache, weight gain, irregular heartbeat, nausea and dizziness. Intramuscular injections are sometimes given at 10 units and sublingual Oxytocin has been used by Dr. Cheney at 10 units up to a maximum of three times a day. Oxytocin should not be used by those who are pregnant.
 
 
Pentoxifylline– Pentoxifylline belongs to a class of drugs called xanthine derivatives and its most common usage is to improve cerebral and peripheral blood circulation. It may also benefit ME/CFS patients by reducing; the cytokine IL-2, lowering NF-Kappa B and downregulating the cytokine TNF-alpha. All three facets of the immune system are thought to be high in ME/CFS patients and potentially contributing to symptoms. Pentoxifylline also has antiviral and further immunomodulatory properties. Dr. Leslie Simpson has noted that Pentoxifylline is useful at reducing cognitive problems and dizziness in ME/CFS patients.
 
Pentoxifylline should not be taken by those who cannot tolerate stimulants. It should also be avoided by those with a peptic ulcer or at risk of haemorrhaging. The drug hasn’t been well studied in ME/CFS patients but in other illnesses is considered safe and well tolerated at 1200mg per day. The standard dose of Pentoxifylline for various non ME/CFS illnesses is 400mg three times per day.
 
 
Rifaximin (Xifaxan)– Rifaximin is an antibiotic that may benefit ME/CFS patients due to eradicating small intestinal bacterial overgrowth (SIBO). SIBO involves healthy bacteria in the large intestine being transferred to the small intestine thus causing gastrointestinal symptoms. Dr. Pimentel found 100% (42/42) of Fibromyalgia patients testing positive to SIBO compared to 20% of controls. The degree of pain experienced by Fibromyalgia patients in this study correlated strongly with the amount of hydrogen seen on the lactulose breath test. Rifaximin may also help ME/CFS patients as it balances gut flora. In vitro, 90% of the 536 strains of anaerobic bacteria tested were inhibited in vitro. Anecdotally, a reasonable number of ME/CFS patients have improved whilst on Rifaximin although many patients have had their symptoms return upon stopping the drug. Interestingly, some ME/CFS patients with no gastrointestinal symptoms improve. Dr. De Meirleir, Dr. Teitelbaum, Dr. Peterson and Dr. Myhill all use Rifaximin on their ME/CFS patients with some only using it after positive test results.
 
Rifaximin is generally well tolerated and only 0.4% of subjects in a traveller’s diarrhea study had to discontinue treatment due to side effects. The most common side effects are gastrointestinal. Long term usage of Rifaximin increases the chances of building resistance to the drug. Some specialists recommend a slightly lower dose of 550mg taken 2 times per day for 8 days. Other specialists recommend doses up to 550mg be taken 3 times per day for 14 days. It is recommended that probiotics are taken after Rifaximin usage.
 
 
Sleep Aids– In the attached link I examine the various prescription sleep drugs that the ME/CFS specialists recommend. Dr. Cheney, Dr. Teitelbaum, Dr. Klimas, Dr. Lapp, Dr. Myhill and Dr. Enlander all have certain sleep inducing and sleep enhancing drugs that they try on their patients in a specific order.
 
 
Vitamin B12 Injections– Despite often having normal B12 as determined by a blood test, ME/CFS patients commonly have low B12 levels in their brain. High levels of B12 being injected can ensure that sufficient B12 crosses the blood-brain barrier. B12 may also benefit ME patients by acting as a scavenger of nitric oxide, a compound that may contribute to ME/CFS symptoms. A poll found that 50%-80% of Dr. Lapp and Dr. Cheney’s ME/CFS patients improved to some degree after taking B12 injections. A study found that ME/CFS patients were much more likely to respond to B12 injections if they had more frequent injections, a higher dose of B12, tried the treatment for longer and were taking oral folic acid. The study also found that the concentrated (5mg/ml) methylcobalamin form of B12 tended to be more effective than the hydroxocobalamin form (1mg/ml). Some specialists prefer the cyanocobalamin form of B12 as it is more stable. If an ME/CFS patient doesn’t respond to B12 injections, they may respond to oral folic or folinic acid. B12 is also available over-the-counter in a sublingual form however this isn’t necessarily as effective as the injectable versions. ME/CFS specialists inevitably opt for injectable B12 over other forms. Dr. De Meirleir, Dr. Lapp, Dr. Teitelbaum and Dr. Cheney are amongst a number of ME/CFS specialists to use this treatment.
 
When taking high doses of B12, a vitamin B complex is recommended to be taken concurrently. Although considered to be a fairly safe treatment, B12 may cause a temporary weakness in some patients. Dosage, type of B12, frequency of injection and method of injection vary depending on the physician’s preference.

 

 

 

Over-the-Counter Treatments for ME/CFS (Non Prescription)

 

Artesunate– Artesunate is a derivation of the herb artemisia and commonly used in the non-ME/CFS realm for its anti-malarial properties. It may benefit ME/CFS patients due to its potential anti-herpesvirus and anti-CMV effects. Using Artesunate, Dr. Cheney has doubled his number of ME/CFS cures and 75% of patients have shown some level of improvement using this treatment. Part of Dr. Cheney’s protocol involves the Artesunate being used concurrently with the herb wormwood.
 
Some ME/CFS patients taking Artesunate have reported dizziness or tiredness. Dr. Cheney recommends the brand Hepasunate be taken on three days of the week. As opposed to swallowing the capsule, he encourages patients to place half the contents of the capsule under their tongue for a period of a minute followed by swishing it around their mouth and spitting the remnants out.
 
 
Benfotiamine and Allithiamine– These are alternate versions of high dose thiamine that may be better absorbed. Anecdotally, many patients have improved as a result of these treatments. Studies have shown that a thiamine deficiency can causes similar symptoms to ME/CFS and these symptoms can be resolved (especially fatigue) after treatment with high doses of thiamine. See ‘Thiamine- High Dose’ for more information about thiamine and ME/CFS.
 
Theoretically, these treatments should be avoided by those who have cancer. Few side effects have been reported by those taking Benfotiamine and Allithiamine. It is difficult to determine a standard quantity for these ‘high dose’ treatments as patients have tried a wide range of doses. Anecdotally, ME/CFS patients online have commonly taken either 50-200mg of Allithiamine or 300-600mg of Benfotiamine.
 
 
Biotin– Biotin deficiency has many shared features with ME/CFS. Several anecdotal accounts are online that mention Biotin greatly benefiting ME/CFS patients. High dose Biotin is currently being studied, with some promising results, as a treatment in progressive multiple sclerosis.
 
Biotin is normally a fairly safe treatment with few side effects noted. The dosages used by ME/CFS patients have often been in the 300mcg-1000mcg range. A neurologist from Massachusetts recommended that an ME/CFS patient take; 100mg of B1 (twice a day), 100mg of B2 and the high dosage of 5000mcg of Biotin for treating post-exertional malaise. This treatment benefited the patient.
 
 
Butyrate– Butyrate may improve ME/CFS patients’ gut symptoms by creating T-cells in the digestive system. It may reduce cognitive symptoms, lower inflammation and enhance the immune system. Studies have shown that butyrate may be beneficial in treating ulcerative colitis and Crohn’s disease symptoms.
 
Butyrate is low in side effects and 1-2 capsules are usually taken with each meal.
 
 
Coenzyme Q10– Coenzyme Q10 is a treatment that when taken with L-Carnitine, has superior effects. These treatments both enhance mitochondrial function and hence may benefit ME/CFS patients. The active version of Coenzyme Q10, Ubiquinol is often preferred. A study found a close association between levels of Coenzyme Q10 and severity of ME/CFS. Dr. Lapp has found that about half of his patients benefit from Coenzyme Q10 generally by around 10%-15%. A University of Iowa study rated Coenzyme Q10 as the leading treatment for ME/CFS with 69% of patients reporting it as beneficial. A study with 20 ME/CFS patients (80% of those deficient in Coenzyme Q10) found 90% had a reduction or complete disappearance of symptoms after 3 months of taking Coenzyme Q10.
 
There is a theory that taking Coenzyme Q10 as two doses throughout the day can increase its efficacy. There also exists a sublingual version of Coenzyme Q10. Alongside the energy boost that Coenzyme Q10 may provide, it occasionally causes insomnia. Those with diabetes or other types of hypoglycemia should be wary of Coenzyme Q10 as it can reduce blood sugar levels. The daily dose that is used generally varies from 50mg to 300mg.
 
 
Cordyceps Sinensis and Shiitake Mushroom– Cordyceps Sinensis may enhance the immune system. A study on healthy subjects found ‘CordyMax’ increased aerobic capacity, reduced fatigue and lowered diastolic blood pressure. Another treatment that is similar to Cordyseps Sinensis is Shiitake mushroom which may increase interferon levels and have antiviral and immunomodulatory benefits. Anecdotally, numerous ME/CFS patients have reported more energy after taking versions of Shiitake mushroom supplements. A Japanese study that used injected ‘Lentinan’ taken from Shiitake mushroom on ME/CFS subjects found patients’ natural killer cell function increased. Recovery of the majority of patients studied took several months. Another study injected Lentinan into ME/CFS patients and found that 6 months of injections was required to normalise natural killer cell activity. Lentinan doesn’t get absorbed orally hence has to be given as an injection. Maitake and Reishi are another two of the many types of mushroom supplements used by ME/CFS patients. A study found that oral Maitake and oral Shiitake mushroom in combination significantly increased natural killer cell function in mice.
 
Most people that take Cordyceps Sinensis experience no side effects however rarely diarrhea and nausea can occur transiently. In the aforementioned study, subjects took 333mg of Cordymax three times per day with meals. Shiitake mushroom supplements may cause gastrointestinal symptoms or a rash. Shiitake mushroom supplements are sometimes used at daily doses between 400mg-1500mg, with this total daily dose broken up into smaller doses taken several times a day.
 
 
Curcumin– Curcumin is a derivation of turmeric. A study found that curcumin benefited mice with ‘CFS.’ Dr De Meirleir has recommended this treatment to some patients. It may reduce cognitive impairment, improve HPA axis dysfunction and have anti-inflammatory and antioxidant properties. A study found that when Curcumin is supplemented with either; olive oil, stearic acid or choline, the brain and blood absorption levels of Curcumin dramatically increase.
 
Side effects from Curcumin usage are rare however if they do occur are generally of a gastrointestinal nature. Dosages used generally fall within the 500mg-1000mg range. Those with illnesses other than ME/CFS have ventured up to 8 grams of Curcumin a day. The absorption levels of the specific type of Curcumin used are relevant when determining a dosage.
 
 
D-Ribose– This treatment may improve mitochondrial function and supply the body with energy. A pilot study found that 66% of ME/CFS patients significantly improved while taking D-Ribose. A follow up study involved 203 ME/CFS and Fibromyalgia patients that completed three weeks of treatment. The patients’ experienced: an average energy increase of 61%, a 37% improvement in well-being, a 30% increase in mental clarity, a 29% enhancement in sleep and a 16% reduction in pain.
 
D-Ribose shouldn’t be used by those with gout as it may raise uric acid levels. Side effects can include nausea, headache and sleepiness. In the above D-Ribose studies, patients took 5 grams of D-Ribose, three times per day. It may be wise to start at a lower dose, to gauge any potential side effects.
 
 
Energy Revitalization System– This formulation contains a broad range of nutrients including a B vitamin complex. It also contains various amino acids, choline, malic acid and biotin. It was developed by Dr. Teitelbaum and it is claimed that it can replace taking 30 tablets in the one formulation. A number of the ingredients probably aren’t of a high enough dosage to have a therapeutic effect on some patients although other parts of this formulation contain reasonable dosages. Many ME/CFS specialists recommend that patients take a multi-vitamin tablet including Dr. Cheney who labels a quality multi-vitamin as “essential.” Energy Revitalization System isn’t a multi-vitamin tablet but rather a powder containing eclectic ingredients targeted at improving patients’ energy.
 
A small number of patients taking this treatment experience gastrointestinal symptoms. The typical dosage is one scoop (20.3 grams) per day.
 
 
Epicor– Studies have shown that Epicor may improve natural killer cell function (which is almost inevitably low in ME/CFS patients) up to 4-fold.  A similar substance, beta-glucan, may regulate other parts of the immune system too. A study that induced mice with ‘CFS’ found that beta-glucan significantly improved the symptoms of the mice.
 
Epicor and beta-glucan are considered to be fairly safe supplements. The standard dosing of Epicor and beta-glucan ranges from 200mg to 3000mg.
 
 
Essential fatty acids (EFA)–  Essential fatty acids include such substances as; flaxseed oil, evening primrose oil and fish oil. The first study to examine EFA usage in ME/CFS patients provided patients with both omega-3 and omega-6, resulting in 85% of the patients showing at least moderate improvement. A second study on ME/CFS patients taking EFA found 90% of patients experiencing a reduction in symptoms. Another study that provided patients with eicosapentaenoic acid (EPA) found that all four patients improved while the same patients didn’t respond to a placebo.
 
Heartburn and gastrointestinal symptoms are some of the most common side effects of fish oil. The recommended dosing of EFA varies depending on what type of EFA product is being used. Fish oil is often used at 3000-4000 mg per day.  
 
 
Far Infrared Sauna– A study on 13 ME/CFS patients using a Far Infrared Sauna found two patients dramatically improve. The other 11 ME/CFS patients had a reduction in physical symptoms, lower levels of pain and reduced fatigue. Another study monitored the effects of Far Infrared Saunas on 10 ME/CFS patients. Average fatigue levels reduced on a 10 point scale from 6.7 to 4.8.
 
It is recommended to hydrate after a Far Infrared Sauna session with electrolytes. Also, many people shower when a session is completed to remove the excess sweat from their body. The Far Infrared Sauna user should also be cognisant of the signs of heat stroke. ME/CFS patients that do trial this therapy should start off for only a short period of time in the Far Infrared Sauna before gradually increasing the time period if they don’t experience side effects. Some patients slowly build up to having a maximum 15-30 minute session per day.
 
 
Fucoidan– There is limited information online pertaining to ME/CFS patients taking Fucoidan. Despite this, over 850 studies on Pubmed detail many effects that may potentially benefit ME/CFS patients. These include; immune modulation, antiviral, anticoagulant and anti-inflammatory effects. A study found that Fucoidan reduced the amount of fatigue experienced by cancer patients.
 
Fucoidan is widely considered to be a safe treatment. Some people have experienced transient diarrhea while taking this treatment. Anticoagulants shouldn’t be used while a patient in on Fucoidan. Studies have found that the efficacy of Fucoidan is largely dose dependant. An osteoarthritis study determined that 1000mg per day had a much better effect on subjects that 100mg per day. Fucoidan has been largely untried by the ME/CFS patient community hence appropriate doses are hard to establish.
 
 
Germanium– A 1988 paper reported that Dr. Greenberg found 25% of his ME/CFS patients showing “substantial clinical improvement” as a result of taking 300mg of Germanium a day. Dr. Maslin in the same paper found 150mg-300mg daily was sufficient to provide significant relief from ME/CFS symptoms in the majority of his patients and found 20% of patients to be non-responders. Dr. Anderson found half of his patients responding favourably to Germanium with doses for some patients needing to be as high as 1 gram.
 
If patients are keen to take high doses of Germanium, they should have regular tests to monitor kidney function. It may be wise for ME/CFS patients to start Germanium at a low dosage and gradually build up to 300mg per day. As the above specialists’ reports indicate, some patients may need high doses, up to 1 gram a day to experience the effects of this treatment. The safer, medicinal form of Germanium is known as organic Germanium-132, the inorganic form is not recommended for supplemental use.
 
 
Hawthorn– Dr. Cheney has been an advocate of Hawthorn and did recommend its use in tandem with the prescription injectable, Nexavir. Hawthorn may improve the heart’s ability to pump blood around the body. Dr. Cheney trialled it on some of his patient and noted that it improved their cardiac output.
 
In low doses, Hawthorn is non-toxic. Side effects are fairly uncommon but may include; nausea, headaches and palpitations. Doses used generally fall between 200mg-1000mg.
 
 
Inosine– The supplement, Inosine, is the active ingredient in prescription medication ‘Isoprinosine.’ A study on the prescription version of this treatment found benefits in 6 out of 10 ME/CFS patients. Dr. De Meirleir believes the supplement Inosine is as effective as the prescription formulation. Inosine is antiviral and an immunomodulator. Dr. Sharp has labelled its prescription cousin as “One of the safest, most cost effective and helpful drugs at our (ME/CFS doctors’) disposal.”
 
Inosine is fairly low in side effects although some patients have experienced insomnia and headaches. Inosine can raise uric acid levels so shouldn’t be taken by those with gout. ME/CFS patients commonly take inosine at a dosage of 500mg three times a day but only on five days of the week. The treatment isn’t taken on 2 consecutive days each week such as the weekend. A pulsing dosing structure of this treatment is recommended so the patient doesn’t build up a tolerance to the Inosine.
 
 
IP-6 (Inositol Hexaphosphate)– The main mechanism of this supplement is to increase natural killer cell activity which is inevitably low in ME/CFS patients. Dr. Conley reports that he has used IP-6 to increase natural killer cell function in dozens of cases of ME/CFS. He notes one patient who went from being unable to work to working a 32-40 hour a week job as a result of taking IP-6. A related treatment that some patients use is Inositol. Inositol may be useful against insomnia and depression.
 
IP-6 is generally low in side effects with the most common being gastrointestinal. It is recommended that this supplement be taken on an empty stomach and twice a day. Some ME/CFS patients start with a lower dose of IP-6 such as 500mg and gradually increase this dosage to a total daily dose between 2-8 grams. The dose is taken at two separate occasions each day.
 
 
L-Carnitine– This amino acid could potentially benefit ME/CFS patients due to improving mitochondrial function. Acetyl-L-Carnitine may be better absorbed by the body than standard L-Carnitine. When taken in tandem with Coenzyme Q10, the positive effects may be magnified. A research centre found that out of 150 ME/CFS patients taking L-Carnitine, 69% noted an improvement in symptoms. A study found 12 out of 18 ME/CFS patients noting a statistically significant reduction in fatigue as a result of taking L-Carnitine. Another study found that 59% of ME/CFS patients taking Acetyl-L-Carnitine improved, 63% taking Propionyl-L-Carnitine improved but only 37% taking both treatments improved. The study noted that Acetyl-L-Carnitine mainly reduced mental fatigue while Propionyl-L-Carnitine was more likely to lower general fatigue. Studies have found ME/CFS patients low in cellular acylcarnitine levels. Deficiency of acylcarnitine can produce symptoms similar to ME/CFS. A study also found that as acylcarnitine levels improved in ME/CFS patients, symptoms improved.
 
L-Carnitine should be avoided by those ME/CFS patients with low thyroid. If side effects do occur, they may be of a gastrointestinal nature. L-Carnitine should be taken with food and recommended dosages range from 1000mg to 2000mg per day. Patients often start off with a lower dose before increasing the dosage if no side effects occur.
 
 
L-Serine– L-Serine is an amino acid that former ME/CFS specialist Dr. Buttfield believes should help 60% of CFS patients significantly. Dr. Vallings found that 5/6 ME/CFS patients benefited from L-Serine supplementation. A study found that ME/CFS patients had “significantly reduced” levels of L-Serine in their urine when compared to healthy controls. The study continued on to note that those ME/CFS patients with low urinary L-Serine levels had mainly neurological symptoms and high levels of pain.
 
L-Serine side effects are fairly rare but may consist of sleep disturbance or gastrointestinal symptoms. Dr. Buttfield’s protocol consisted of beginning patients on 500mg of L-Serine in the morning and increasing this dosage to 2 grams per day.
 
 
Magnesium– The majority of ME/CFS specialists incorporate either oral magnesium or magnesium injections into their treatment protocol. Dr. Cheney believes magnesium can benefit ME/CFS patients due to; enhancing energy, improving sleep and lowering muscle pain. He advocates oral magnesium glycinate due to its ability to cross the blood-brain barrier and also be absorbed into cells. Other ME/CFS specialists prefer magnesium citrate due to its possible higher levels of bodily absorption.
 
Another facet of Dr. Cheney’s advocacy of magnesium glycinate is that this treatment is less likely to cause gastrointestinal symptoms. Other forms of magnesium are more likely to cause diarrhea. Magnesium should be taken with food and dosages should begin at low levels before increasing to the 200mg-400mg range.
 
 
NADH– This treatment is a form of coenzyme 1. A study found that 31% of ME/CFS patients improved while taking NADH in comparison to 8% of the control group improving. 18 out of 25 (72%) of ME/CFS patients enrolled in the longer follow up version of this study noted improvements. There is some evidence that it may take up to 6 months before certain ME/CFS patients respond to this treatment.
 
Side effects tend to be rare but mild overstimulation is possible. NADH should be taken on an empty stomach, before breakfast. Recommended dosages range from 5mg up to 20mg per day.
 
 
Naphazoline HCL– Dr. Goldstein, who was an ME/CFS specialist, always tried Naphazoline HCL 0.1% eye drops as an initial treatment when a patient stepped into his office. He claimed that 20% of patients benefited from this treatment and in those patient who benefited, the benefits were remarkable and immediate. He theorised that those patients in the cohort of having severe anxiety were the most likely to respond. In some countries such as Australia, Naphazoline HCL is available over-the-counter.
 
The delivery process of this treatment involves placing a drop in each eye. Due to the nature of Naphazoline HCL, any benefits will be felt almost instantaneously. One of the most common side effects is local irritation. The occurrence of more serious side effects from this treatment is unlikely but may include; dizziness, headache or nausea. The dosage of the Naphazoline HCL eye drops used should be 0.1% and not 0.01%.
 
 
NeuroProtek– NeuroProtek contains a number of eclectic supplements; luteolin, quercetin and rutin in tandem with the antioxidant, olive kernel oil. Anecdotally, many ME/CFS patients have reported a reduction in cognitive impairment as a result of taking NeuroProtek. A drawback is that often the cognitive impairment returns when the patient ceases taking the treatment. Neuroprotek may be able to normalise mast cell function.
 
Side effects of NeuroProtek are rare however caution is advised if the patient is concurrently taking drugs that are metabolised by the liver as NeuroProtek may alter the blood levels of these substances. The dosage of NeuroProtek is dependent on the patient’s weight, with a daily dose being 2 capsules taken per 20kg (44lbs) of body weight. The maximum dose, regardless of body weight is 8 capsules per day. Capsules should be taken with food and the dosage spread out across the day.
 
 
Nicotine Gum– Former ME/CFS specialist, Dr. Goldstein wrote fondly of Nicotine Gum as a treatment for ME/CFS. He noted that patients experienced an improvement in energy, cognition and mood as a result of this treatment although did caution that some patients may get worse. It potentially benefits ME/CFS patients due to inhibiting brain inflammation. Several patients have noted an improvement in cognition and increase in energy as a result of this treatment.
 
Nicotine Gum can be detrimental to those with Crohn’s disease. Dr. Goldstein stipulates that occasional patients will have a worsening of ME/CFS symptoms as a result of taking this treatment. If a patient does improve on this treatment, benefit will be noted soon after taking the gum. One ME/CFS patient took a week before experience more energy. Nicotine may increase blood pressure which may be detrimental if an ME/CFS patient has high blood pressure. Longer term use of nicotine is also conducive to health problems such as addiction, periodontal problems and hair loss. If this treatment is trialled, a low starting dose is imperative.
 
 
Oxymatrine (Equilibrant)– Equilibrant is Dr Chia’s own formulation of Oxymatrine that also contains; Astragalus, Olive Leaf, Liquorice and Shiitake Mushroom. Oxymatrine, derived from the Sophora plant, is thought to be effective against enteroviruses. Dr. Chia has trialled Oxymatrine on 500 ME/CFS patients and has found approximately 52% of his patients improve as a result of taking this treatment.
 
Common side effects of Oxymatrine can include headache, fatigue or an increase in ME/CFS symptoms. Oxymatrine should be avoided by those with autoimmune tendencies or seizure disorders. A low starting dose of Oxymatrine is essential for ME/CFS patients and the dosage should only be titrated upwards after a week.  The maximum dosage of this treatment is in the realm of 200mg taken in the morning and 200mg taken in the afternoon. Dr. Chia’s Equilibrant doesn’t list the amount of Oxymatrine in the product however the recommended initial dosages of this product is 1 tablet per day for 1-2 weeks. This is followed by a gradual increase of dose, with patients taking up to a maximum of 6 tablets per day.
 
 
Piracetam– Piracetam is a supplement that specifically targets enhancing cognition. It may also benefit ME/CFS patients due to increasing blood circulation. A study that gave fatigued patients (not necessarily those with ME/CFS) Piracetam and Cinnarizine (an antihistamine) found that patients’ physical fatigue significantly reduced. There exist several similar products to Piracetam that may also benefit ME/CFS patients and these are classed as nootropics.
 
In non-ME/CFS studies, Piracetam has rarely caused side effects. One study ascertained that 12% of subjects experienced sleep disturbances while taking this treatment. If a headache does occur while a patient is taking Piracetam, Choline may be a beneficial tandem treatment. Anecdotally some ME/CFS patients have stated that they can only tolerate a small dose of Piracetam- in the 100mg range. Other patients even find this dose too stimulating. Starting at the normally recommended dosage is not recommended for those with ME/CFS. The dosage of Piracetam used for other indications can be up to 20 grams per day. ME/CFS patients generally require much smaller dosages in the 0.8-4.8 gram range. This dosage is spread out across the day and taken at three different occasions at 8 hour intervals. Different countries have various classifications on Piracetam pertaining to its over-the-counter or prescription status.
 
 
Post-Exertional Malaise Treatments– This debilitating and central symptom of ME/CFS is often overlooked by doctors. There exists a range of treatment worth trying that I’ve written about in the attached link that benefit patients to varying degrees once in a ‘crashed’ state. These include; Hydralyte iceblocks, liquorice, D-Ribose, electrolyte solutions, leg elevation, massage, meditation, warm baths or cold baths.
 
 
ProBoost– Also known as thymic protein A, a study found 16 out of 23 ME/CFS patients experienced a normalisation of immune function as a result of taking this treatment. There was a corresponding improvement in the clinical ME/CFS symptoms of patients in this study. Another study examined the use of thymic protein A in 6 ME/CFS patients with high EBV titre levels. Patients experienced an increase in energy and required less sleep to function. There exist several reports online of patients greatly benefiting from ProBoost. Many ME/CFS patients who feel run down or on the precipice of a virus take ProBoost.
 
Side effects as a result of taking ProBoost are rare with occasional patients reporting mild, flu like symptoms when they start this treatment. The dosage used varies depending on whether the patient is taking it as a maintenance dosage- 1 packet a day or are fighting off an acute infection- 3 packets per day. Dr. Teitelbaum recommends that ME/CFS patients take one packet of ProBoost, 3 times a day.
 
 
Propax with NT Factor– This product contains a number of treatments all in the one formulation. Many of these lone treatments are individually used by ME/CFS patients including; quercetin, L-Glutathione, NAC, grape seed extract, various B supplement and NT factor. A study that was ominously run by the company that produces this product found that those with the symptom of severe fatigue (not necessarily ME/CFS) experienced a reduction in fatigue by on average 40%. Another study found Propax with NT Factor reduced the fatigue experienced by cancer patients. Propax with NT Factor is potentially a form of ‘lipid replacement therapy’. This entails repairing damage to a patient’s mitochondrial membranes. A study examined lipid replacement therapy’s efficacy on ‘moderately fatigued patients.’ As subjects mitochondrial function improved while taking lipid replacement therapy, their fatigue proportionally reduced.
 
Propax with NT Factor is considered to be a safe product with gastrointestinal symptoms rare but possible. It is recommended that the packet be consumed 2-3 times a day. The tablets in the formulation can be taken with or without food and the soft gel capsule that contains omega-3, EPA and DHA should be taken with food.
 
 
Ranitidine– Ranitidine is a treatment that former ME/CFS specialist Dr. Goldstein found benefited those with infectious mononucleosis. He then began using this treatment on ME/CFS patients with some success. If Ranitidine is not available over the counter in a country, often the alternative Cimetidine is. Dr. Goldstein has found that about 90% of mononucleosis cases respond to Cimetidine. When an ME/CFS patient does respond to one of these drugs, Dr. Goldstein notes that the recovery is remarkable. Approximately 20% of Dr. Goldstein’s ME/CFS patients respond to this type of drug.
 
Stimulation and headaches are two of the most common side effects of Ranitidine treatment. Dr. Goldstein recommends that 150mg of Ranitidine be taken twice a day. The alternative, Cimetidine, should be taken at 300-400mg. Dr. Goldstein has written that it may take from one hour to one week before a patient notices whether this treatment is working for them.
 
 
Selenium (high dose)– Numerous patients online have noted great benefit from this treatment. The symptoms that have generally improved in these patients are cognitive ability and energy. High dose Selenium may benefit ME/CFS patients due to its antiviral and strong antioxidant properties.
 
Taking high dose Selenium for more than several months is not recommended as it may increase the chance of toxicity, although Selenium toxicity generally occurs at higher doses (the 2400-3000mcg range). Overdosing on Selenium can cause numerous symptoms. The recommended dosage of the high dose Selenium protocol is between 400-800mcg a day. Some ME/CFS patients have noted side effects if they increase the dosage past 400mcg. The Selenium should be taken on an empty stomach to increase absorption. Yeast-free selenomethionine is thought to be the best form of Selenium to take although other forms may benefit certain patients more effectively.
 
 
Sleep Aids– In this link I present various ME/CFS experts’ opinions on sleep aids including many over-the-counter formulations.
 
 
Sulforaphane– This compound may benefit ME/CFS patients due to shifting the immune system from Th2 dominant to Th1 dominant. Sulforaphane is also an antioxidant, neuroprotective, defensive against oxidative stress and may improve mitochondrial function. It has been studied in autism and benefited those who took it through a mechanism the authors suspected may be due to inducing a “fever effect.”
 
In the aforementioned autism study, those taking Sulforaphane experienced a tiny increase in their liver enzymes. There is quite some conjecture about the amount of Sulforaphane the body absorbs. This is partly due to the possible discrepancy between the specific forms of Sulforaphane ingested. It is therefore difficult to pinpoint a commonly used dosage.
 
 
Thiamine (high dose)– Anecdotally, some ME/CFS patients have reported benefits from taking high doses of thiamine (vitamin B1). A small study of Fibromyalgia patients found all 3 patients benefiting from high dose thiamine treatment. Thiamine deficiency (which can be caused by a defective enzyme system) can produce similar symptoms to ME/CFS. A study found that fatigue associated with ulcerative colitis and Crohn’s disease can be caused by a thiamine deficiency and that high doses of thiamine resolved this fatigue. Despite this, across multiple studies examining various disease state, patients have normal blood thiamine levels yet improve significantly when taking high dose thiamine. A study has speculated that this may be due to low cellular thiamine transportation or enzymatic problems.
 
The three Fibromyalgia patients studied experienced no side effects as a result of high dose thiamine. Patients with other disease states taking high dose thiamine have reported insomnia and tachycardia. In the Fibromyalgia- high dose thiamine study, patients started at 600mg of thiamine a day and gradually increased this dose. Abrupt improvement was seen when patients reached 1800mg a day. Anecdotally, ME/CFS patients that have responded to high dose thiamine seem to have an optimal dose that varies from patient to patient. The challenge is to find this optimal dose without exceeding it and experiencing any side effects. If a patient doesn’t respond to thiamine, they may benefit from Benfotiamine or Allithiamine, which may be better absorbed.
 
 
Vagus Nerve Stimulation– Dr. VanElzakker has theorised that the vagus nerve being infected could explain many of the features of ME/CFS. The vagus nerve has been implicated in several other illnesses such as epilepsy, with stimulation of the nerve proving beneficial. A study implanted Fibromyalgia patients with a vagus nerve stimulation device with the authors concluding that it was a “useful adjunct treatment.” A less invasive measure to stimulate the vagus nerve involves attaching a TENS machine’s electrode pads to the tragus part of the ear.
 
 
Vitamin D– Vitamin D deficiency can often be a secondary problem that arises when ME/CFS patients are unable to get proper supplementation from sunlight. A retroactive study of 221 ME/CFS patients found that Vitamin D levels were “moderately to severely suboptimal in CFS patients.” Numerous patients online have benefited to some degree from Vitamin D supplementation. Dr. Lapp recommends Vitamin D3 to almost all of his ME/CFS patients.
 
Vitamin D side effects are rare at normal doses yet high Vitamin D may cause weakness, headaches or gastrointestinal symptoms. Some patients gain Vitamin D from sunlight or through daily lower level supplementation in the 1000-2000IU range that is available over-the-counter. To definitively raise Vitamin D levels, a single or once a month for several months prescription dose may be required. This may on occasions be as high as 100,000IU. Blood tests can monitor Vitamin D levels yet there is some conjecture about what levels are considered suboptimal. Studies have suggested that those with any form of chronic illness should try and maintain higher vitamin D levels than the healthy population.

 

About These Lists

The key purpose behind creating the above lists was to show patients who have lost hope that there are treatment ideas for this illness. Another purpose of these lists was to compile much of the information that was spread haphazardly across this blog in a centralised and easy to access location.
 
As I continue to write about other ME/CFS treatments on my blog, I will add them to this treatment page. There are many more treatments that I didn’t include in the above lists but ME/CFS patients may benefit from. The following are just some treatments that may help ME/CFS patients based on either study results or their use by some ME/CFS specialists; various probiotics, Glutathione, N-Acetyl Cysteine, methylation cycle treatments, MAF 314, IV saline solution, Gamma Globulin injections/IV, Lidocaine IV, Valtrex, Valcyte, Ergoloid, Levofolinic Acid, Nifedipine, Galantamine, Ampligen and Rituximab.
 
There seems to be a degree of disease heterogeneity across the entire collection of ME/CFS studies and indeed often within single ME/CFS studies. Some studies require that just the overly broad Oxford Criteria be met for patient inclusion. In contrast, other studies are narrower and demand more severely affected patients sharing more common symptomology. Many ME/CFS studies aren’t adequately funded and hence; don’t have a high number of participants, lack a placebo group and aren’t considered high quality. If these idealistic studies existed, I would have written more about these and the corresponding treatments but unfortunately they don’t.
 
It is for the above reasons that I often place a greater emphasis on what an ME/CFS specialist (who has stringently diagnosed ME/CFS) has found the clinical response rate of a treatment to be e.g. 30% of responders. This is why I have attempted to include as many clinical observations and comments from ME/CFS specialists as possible in the above lists.
 
Finally, I should emphasise that patients should always consult with their physicians prior to taking any treatment. I am not a doctor and nothing on this blog should be construed as medical advice. It is imperative that patients and their physicians are aware of possible side effects, including those not listed before starting any treatment. Patients should also be aware of possible interactions between any treatment they commence and their current medications. Some treatments listed are recommended for short term use only while other treatments may require up to 6 months of usage before effects may be noticed. ME/CFS patients are renowned for having a higher sensitivity to treatments than patients with other diseases. In many cases it is wise to begin treatments at a lower dose to mitigate the chance of more severe side effects.

My Experience With Heparin For ME

In my previous blog entry, found here, I wrote about the general theory of heparin as a treatment for ME. This blog entry will detail my personal rationale for trying heparin. I will essentially illustrate why I believed this treatment was in theory suitable for me. Following this, I will describe the results of my heparin trial.

 

APS Antibodies

Several months ago, I had a blood test performed for antiphospholipid syndrome (APS). The results came back as follows:
 
Cardiolipin IgG Ab= 26     (normal is less than 12)

Beta 2 glycoprotein IgG Ab= 58     (normal is less than 20)
 
The footnote beneath the test read: “This result is consistent with antiphospholipid syndrome.” Thus begun my dalliance with hypercoagulation and subsequently heparin.
 
APS is an autoimmune condition. The hypercoagulation aspect of APS is caused by the APS antibodies. A diagnosis of APS generally requires 1 out of 3 positive antibody tests (I had two positive).  It also entails the occurrence of a past thrombotic event (which I haven’t experienced) or in women, pregnancy complications. The actual criteria are far more complicated and nuanced than this. Three papers by Berg et al. that I wrote about in my last blog entry, discuss why some ME patients have these antibodies and how they may indicate hypercoagulation in this patient population.
 
 

Raynaud’s Phenomenon

My former and now retired ME Specialist, stated that I had the coldest hands out of his 500 ME patients. My hands and feet have been consistently icy throughout the duration of my illness.
 
According to the paper ‘Low Level Activation of Coagulation with Coagulopathies in the Etiology of CFS / FM and Chronic Illnesses. An Explanatory Model.’ “Increased SFM in the plasma may increase the plasma viscosity. Increased plasma viscosity decreases blood flow. Decreased blood flow may cause some end organ dysfunction. This may explain the Raynaud’s phenomenon of cold hands and/or cold feet.” Essentially the paper explains that the cold hands and feet of ME patients may be due to hypercoagulation.
 
 

SPECT Scan

My SPECT scan showed hypoperfusion in the brain.
 
Kato et al. in the 1997 study ‘Hypoperfusion of brain single photon emission computerized tomography in patients with antiphospholipid antibodies’ found SPECT scan hypoperfusion in headache patients with APS antibodies. They concluded that the SPECT scan results may be caused by “microarterial thrombosis, microvenous thrombosis or vascular spasms.”
 
 

Sed Rate

Since the onset of my ME, my sedimentation rate (sed rate) has been most commonly 2.
 
Referring to CFS and hypercoagulation, Researcher David Berg writes, “The normal range for sed rates should start above 3 or 4. Values below this are correlated with high SFM values. As the Soluble Fibrin Monomer (SFM) goes up in the plasma, these molecules form dimers (2 stuck together). This physically blocks the RBCs from settling out of the plasma, thus a low sed rate. The only other clinical condition to demonstrate low values involves paraproteins in the plasma such as in a cancer patient.”
 
 

Cold Water Therapy

The only treatment that has provided me with any significant improvement towards my ME symptoms has been immersing myself in cold water. Early on in my illness, this treatment would act like an elixir for several hours before wearing off. Eventually, I failed to respond to cold water therapy.
 
The following information from Professor Kakkar is from a tertiary source. Professor Kakkar of the Thrombosis Research Unit in Europe found poor blood circulation is CFS patients, this causes a reduction in oxygen supply to the brain and muscles. Professor Kakkar suggests that the production of the normal blood thinning enzyme TPA is reduced, as well as certain blood clotting proteins. Interestingly, Professor Kakkar advocates thermo regulatory hydrotherapy (TRHT), i.e. cold baths as the treatment for this poor circulation. Berg believes heparin is a more effective treatment.
 
 

Why Have I Been Treatment-Resistant?

I have tried hundreds of different treatments for my ME. Many of these treatments cause improvement in ME patients however the only treatment to significantly benefit me has been the cold water therapy, which as mentioned above, wore off. It is fairly unusual for an ME patient not to respond to the plethora of treatments I have tried. The hypercoagulation hypothesis is consistent with my non-responding status. CFS specialist Dr. Teitelbaum writes, “Using the blood thinner heparin has been able to help half of those who failed all other treatments.” He continues writing that “I find that about half of my patients with the most severe and refractory symptoms of CFS/FMS get better with this treatment.”
 
 

Coagulation issues

Prior to getting my blood drawn, I drink 1 litre of water. Despite this, the blood pathology nurse regularly comments that my blood is not flowing well and asks if I have consumed any water at all. Several patients online that have tested positive to hypercoagulation have also reported problems with their blood being drawn.
 
 

Hypercoagulation and Genetics

My 23 and ME genetic data lists venous thromboembolism as my highest-risk health condition relative to average. Based on my genes, my risk is 2.90x the norm. “CFS &/or FM patients who have a hereditary deficiency for thrombophilia or hypofibrinolysis may be unable to control thrombin generation properly.” This is according to the Berg et al. paper, ‘Chronic Fatigue Syndrome (CFS) &/or Fibromyalgia (FM) as a Variation of Antiphospholipid Antibody Syndrome (APS): An Explanatory Model and Approach to Laboratory Diagnosis.’

 

 

Heparin-CFS Studies

I wrote in more detail about the heparin studies on CFS patients in my last blog entry. However I will now briefly outline the results of these studies. In the first study, 15/16 CFS patients benefited from heparin treatment either moderately or significantly. The second study found that on average, the 60 CFS patients improved by 85% while taking heparin.

 

Several of the above reasons for trying heparin are spurious and probably examples of my own confirmation bias. I hoped that the above pieces of eclectic evidence supporting heparin benefiting me would slot together like a jigsaw.
 

 
 

My Experience with Heparin

I was somewhat undecided over which type of heparin to inject. Unfractionated heparin was mainly utilised in the CFS studies and Dr. Teitelbaum used this type. It did however have the negative potential of having more side effects. Low molecular weight heparin is considered to be safer, yet due to only being recently introduced into the USA, it is less tried on ME patients. Ultimately, I used the unfractionated heparin.
 
On the 7^th of July, I began the heparin injections, subcutaneously around my stomach. The dosage was 5000 IU, twice a day (a total of 10,000 IU a day). I would inject upon waking and again just before sleep. I also began taking 500mg of bromelain in the morning and 500mg in the afternoon as it helps improve fibrinolysis. David Berg’s protocol incorporates it for certain patients, depending on their blood test results.
 
After 3 weeks on the heparin, I had failed to notice any positive or negative effects. I therefore began taking piracetam concurrently. Piracetam is a nootropic and a study found that when piracetam is taken with heparin, the effects of both treatments are enhanced. I started at a low dosage of piracetam and gradually titrated this number upwards to a maximum of 4.8 grams (1.6 grams taken three times a day). I first tried piracetam 5 years ago and experienced no real effects. I have written about piracetam for ME here.
 
After 3 weeks of heparin, I gradually began to increase the dosage upwards to a maximum of 7,500 IU twice a day (15,000 IU total a day). Dr. Teitelbaum has patients maximise their heparin dosage at 8,000 units twice a day (16,000 IU total a day), if their blood work remains normal. I did have regular blood tests while on the heparin.
 
On the 10^th of August, I ceased the heparin injections. After 5 weeks, I had not managed to note one iota of improvement. Alternately, I didn’t experience any side effects either. The patients Dr. Teitelbaum treats with heparin tend to improve within 2 weeks. The Berg et al. study patients drastically improved within 2-4 days of commencing treatment. I was never planning on trialling heparin for an extended period of time and I believe 5 weeks was sufficient to prove that it was not working for me.

 

APS Blood Test Meaning

I believe the abnormal APS blood tests may provide some clues into my ME etiology. This study by Hokama et al. found cardiolipin antibodies in a high portion of CFS patients. The results varied depending on which cardiolipin antibody was being tested. My cardiolipin IgG levels were 26 (normal is less than 12). 4/40 CFS patients tested in the study had positive IgG levels. The Hokama et al. study found 95% of CFS patients testing positive to cardiolipin IgM antibodies. The authors’ conclusion writes “…suggesting that CFS may be an autoimmune condition.” The paper also states that CFS patients may aim to suppress the cardiolipin antibodies in their blood. The authors continue on to argue that this may be achieved through Rituximab usage because “Rituximab may serve as an effective therapeutic agent for ameliorating the symptoms of CFS.” It is interesting that Rituximab is now emerging as a promising treatment for ME.
 
My Beta 2 glycoprotein IgG levels of 58 (normal range is less than 20) is most commonly associated with APS. Levels of 20 of greater exceed the 99^th percentile. The precise meaning of this test is complicated but it can also be indicative of an autoimmune disease.
 
 

Conclusion

Heparin was a treatment that I held lots of hope for. My above abnormal APS blood test results fitted in well with the Berg et al. papers and the hypercoagulation hypothesis. My peripheral justifications for trialling heparin such as my Raynaud’s phenomenon, brain hypoperfusion and low sed rate coupled with my various other idiosyncratic symptoms posited heparin as the perfect treatment for me.

 

My hopes of improving as a consequence of taking heparin were dashed in a sluggish manner. Day-by-day I failed to improve on the injections until after 5 weeks I thwarted my heparin therapy. Most treatments I trial are directed somewhat at me but more broadly the generic ME patient- whomever he or she is. This was a treatment that seemed tailor-made for my symptoms and blood test results. From a different perspective, heparin is a risky treatment and I am pleased that I didn’t experience any side effects. It is unfortunate that it didn’t work, although I am now quite accustomed to ME treatments not working for me! I am hopeful that my APS blood test results can provide an inkling into the lingering mystery that is my ME.

 

 

Heparin for ME

Heparin is an anticoagulant drug that may be useful to some ME patients. It is typically used in the prevention and treatment of both pulmonary embolism and deep vein thrombosis. It has been theorised that ME in some instances may be caused by a hypercoagulable state and thus heparin would treat this. I will; examine the heparin studies on ME patients, present the opinions of ME experts on heparin and detail which patients may benefit from either heparin or an alternative anticoagulation treatment.

The theory

The human body’s coagulation process is complicated. The ME-coagulation theory is doubly complex and a simplified theory describing it is as follows. Patients initially are struck down with an infection such as; HHV-6, EBV, CMV, chlamydia pneumonia, a tick borne disease or another pathogen. Research involving David Berg suggests that numerous infections can instigate the body’s blood clotting system. This may target those people with an acquired or genetic coagulation defect. After the clotting process is activated, the body creates ‘soluble fibrin monomers’ (SFM). These SFM are analogous to sheets that cover the blood vessels. The resultant impairment of blood circulation is then responsible for ME symptoms.

 

The studies

The first study by Berg et al. was published in 1998 and titled ‘Is CFS/FM due to an Undefined Hypercoagulable State Brought on by Immune Activation of Coagulation? Does Adding Anticoagulant Therapy Improve CFS/FM Patient Symptoms?’ The full paper can be found here. 20 CFS/Fibromyalgia patients were involved in this pilot study however there was no control group. The patients were tested for various coagulation measures. 90% had an abnormal ‘sonoclot rate’, 88% had abnormal ‘SFM’, 48% had abnormal ‘fibrinogen’ and 60% had abnormal ‘platelet activation’.

 
16 of the patients with positive ‘baseline studies’ were treated with placebo for a week followed by heparin. The heparin was administered subcutaneously twice a day and ranged from 5000 units to 8000 units. After one month, the subjects rated their subjective improvements. All 7 of the fibromyalgia patients improved. 1 patient noted some improvement, 3 had moderate improvement and 3 experienced significant improvement. All 9 of the CFS patients improved. 4 said they had moderate improvement whilst 5 had significant improvement. The paper continues on to state that most of the patients began to feel like their “old selves” within 2-4 days of commencing the heparin treatment.

 
The second study Berg et al. published was in 1999 and titled ‘Chronic Fatigue Syndrome (CFS) &/or Fibromyalgia (FM) as a Variation of Antiphospholipid Antibody Syndrome (APS): An Explanatory Model and Approach to Laboratory Diagnosis.’ The full paper can be found here.  A blinded ‘prospective’ study is detailed within this paper. It contained 54 CFS/Fibromyalgia patients and 23 controls. Five specific coagulation tests were performed on all subjects and two positive tests were required to be classified as having coagulation problems. 94% of the CFS/Fibromyalgia patients were positive for hypercoagulation, in contrast to just 4% of the controls testing positive.

 

The Third paper by Berg et al. was titled ‘Low Level Activation of Coagulation with Coagulopathies in the Etiology of CFS / FM and Chronic Illnesses. An Explanatory Model.’ The full paper is behind a paywall but can be accessed here for free. This paper claims that in excess of 3000 patients with chronic illnesses have been tested for coagulation problems and over 80% of these patients have tested positive. The paper also mentions that genetic studies have found a 2-10 fold increase in coagulation protein defects among CFS/fibromyalgia patients and others with a chronic illness. The paper also alludes to ‘unpublished data’ that shows having SFM in the blood may cause very low sedimentation rates (in the 0-4 range).

 
The paper also refers to a retrospective study involving a cohort of 60 CFS/fibromyalgia patients. The subjects were given 5000 units subcutaneously of heparin, twice a day for an average of 8 months. The average improvement on a scale of 1-10 was 8.5, equivalent to an 85% improvement.

 

A Negative study has also been published by Kennedy et al. The 2006 study was titled ‘Is chronic fatigue syndrome associated with platelet activation?’ The full study can be found here. The study included 17 ‘CFS’ patients who fulfilled the contentious Fukuda criteria as well as 16 controls. The study found no coagulation abnormalities in the CFS patients studied.

 

What the ME Specialists Say

Dr. Teitelbaum has written “Using the blood thinner heparin has been able to help half of those who failed all other treatments.” He continues writing that “I find that about half of my patients with the most severe and refractory symptoms of CFS/FMS get better with this treatment.” Dr. Teitelbaum has found that almost every CFS patient he has tested to be positive for hypercoagulation. He does however stipulate that he hasn’t tested healthy controls to compare his results. Dr. Teitelbaum also warns about the dangers of heparin treatment and warns that it is a riskier drug than most of the other drugs he recommends. He tends to use it as a last resort. Dr. Teitelbam is also not 100% convinced in the hypercoagulation hypothesis. He speculates that another feature of heparin may be responsible for the positive effects on CFS patients such as its antiviral properties.

 
Dr. Cheney mentions heparin in a talk given in the year 2000. He speaks of its ability to shift the immune system from Th2 dominant to Th1. This may potentially benefit ME patients with a Th2 shifted immune system. Dr. Cheney only recommends heparin if the patient tests positive to hypercoagulation. He has found approximately 50% of his patients testing positive.

 
Dr. Myhill is not an advocate of heparin in ME patients. She has trialled heparin usage in 4 of her patients with no success. She cites the aforementioned negative Kennedy et al. study as evidence against hypercoagulation being a factor in ME.

 
 

Testing

When it comes to hypercoagulation testing and ME, things can become complicated. It has been suggested by David Berg that any ME patient with cold hands and feet/Raynaud’s phenomenon and a low sedimentation rate be tested for hypercoagulation. Berg, who introduced the concept of specialised coagulation testing has found sedimentation rates “below 4 or 5” indicative of hypercoagulation in ME patients. Sedimentation testing is a standard blood test that is routinely done with most normal blood tests. Most ME patients will probably have this test on file and it is commonly listed as ‘ESR.’

 
The coagulation tests so far mentioned in the above studies and requested by the ME physicians have been specialised and done by the Hemex laboratory. They were taken over by Esoterix Laboratory Services who now do the coagulation tests and are based in the United States. This is considered the gold standard test in hypercoagulation.

 
Antiphospholipid antibody syndrome (APS), also sometimes referred to colloquially as Hughes’ Syndrome is an autoimmune disease that is characterised by blood coagulation. Standard laboratories around the world can test for APS. The studies and papers by Berg et al. above refer to their findings in ME patients as a “Variation of Antiphospholipid Antibody Syndrome.”  The papers continue on to mention that “Antiphospholipid (APL) antibodies have been long associated with a hypercoagulable state, involving both procoagulant activity as well as inhibition of anticoagulant and fibrinolytic activity.” One of the APS antibodies that can be readily tested for is called ‘beta-2-glycoprotein.’ This according to Berg et al. can trigger the chain of clotting. The other subtests and their implication in APS are detailed here.
 

 

Heparin Protocols

There exist several theories pertaining to the best methods of taking the heparin once hypercoagulation has been established in an ME patient.

 
Dr. Teielbaum does not mention what dosage of heparin he starts his patients on however if the patient doesn’t improve and the PTT blood test is still normal, he increases the dose to a maximum of 8000 units twice a day (a total of 16,000 units a day.) The heparin is administered by subcutaneous injection for the first six weeks. He switches them to nose spray heparin or sublingual heparin. Dr. Teitelbaum prophesizes that patients should start to feel better around the 10-14 day mark of treatment. He adds a 6-12 month course of either antibiotics such as doxycycline or antivirals depending on laboratory results. These are taken while the patient is still on heparin. Dr. Teitelbaum has his patients get a platelet count and PTT blood test every 3 days for the first 9 days after commencing heparin therapy and every week thereafter.

 
David Berg developed a protocol for treating ME patients for hypercoagulation and this can be found here. His system involves heparin being taken for 180 days. Transfer factor is taken from day 30-120 and antibiotics from day 30-90. If a patient has high Lp(a) or PAI-1 levels, he recommends bromelain be taken from day 1 to day 120.

 
Ken Lassesen has a model of ME that incorporates the hypercoagulation aspect. He has written about this here and here. He writes that the cause of the poor blood flow that is shown in many ME patients SPECT scan results may be due to hypercoagulation. He refers to a study in which the nootropic piracetam was taken concurrently with heparin. The accumulative effects of piracetam plus heparin were more beneficial to blood flow in the brain than the theoretical adding of piracetam and heparin. In other words, the piracetam and heparin complemented each other to combine to a greater efficacy.

 

Type of Heparin and Dosage

There exists two types of injectable heparin used by ME patients. The first is unfractionated heparin (UFH). Most of the above studies used UFH and Dr. Teitelbaum used this type on his patients. Due to the short half-life of UFH, it requires subcutaneous injection twice a day. The dosage used varies but generally starts at around 4000-5000 units twice a day in a 0.2ml-1ml solution. Berg has stated that patients less than 68kg (150lbs) should start at 4000 units twice a day. In contrast, those over 68kg (150lbs) should begin their dose at 5000 units twice a day. Some specialists increase this up to a maximum of 8000 units twice a day if bloodwork remains normal. It is imperative to monitor UFH usage via blood tests. As mentioned earlier, Dr. Teitelbaum has his patients get a platelet count and PTT blood test every 3 days for the first 9 days of UFH treatment and every week thereafter. Dr. Teitelbaum instructs patients to use an insulin syringe to inject the UFH while others recommend using a tuberculin syringe.

 
The second type of subcutaneous, injectable heparin is known as low molecular weight heparin (LMWH). This variant is more predictable than UFH and is generally considered to be safer. The studies on ME patients and heparin usage are largely void, primarily due to LMWH more recently being introduced to the United States. Berg recommends patients under 68kg (150lbs) taking 30mg of LMWH in the morning. He encourages those over 68kg (150lbs) to take 30mg of LMWH in the morning and 15mg at night. Patients taking LMWH may require an anti-factor Xa activity blood test if they have other medical conditions such as renal impairment.

 
Sublingual UFH is another alternative for hypercoagulation. Ken Lassesen has written that this form can be of equitable effectiveness. It requires 2 minutes under the tongue before being spit out. After 6 weeks of UFH subcutaneous injection treatment, Dr. Teitelbaum has patients switch to either sublingual heparin or heparin in the form of a nasal spray.

 

Side effects

Heparin-induced thrombocytopenia (HIT) is a potential side effect of heparin treatment. There is a lower likelihood of this occurring if the patient takes LMWH. Several studies have examined the risk of HIT with heparin usage and the chances of this occurring varies depending on the disease studied. The chance of LMWH causing HIT is fairly remote however there is a higher chance of UFH causing HIT. HIT causes a low platelet count and is most likely to occur 5-14 days after commencing heparin therapy. Vitamin D and calcium supplementation may reduce the chances of HIT occurring.

 
If Heparin is used for an extended period, a DEXA bone density scan should be performed. It is also imperative to have kidney and liver function tests prior to commencing heparin treatment. Those who have had a peptic ulcer should not take heparin. I should emphasise that heparin treatment is a riskier treatment than most other ME treatments. It is essential that a doctor monitors the progress of the treatment and is aware of the potential dangers.

 
 

Supplements

The ME-hypercoagulation link, in some cases, can theoretically be treated without heparin and with supplements. Dr. Teitelbaum has written that the anticoagulation supplements his patients have tried have failed to yield any positive results. Despite this, there exists numerous accounts online of ME patients benefiting from anticoagulant supplements. Whether this is due to the supplements effects on coagulation or because of some other mechanism is not known. The supplements should not be taken with heparin due to the risk of excessive bleeding.

 
Nattokinase is an enzyme that is derived from the fermented soybeans called Nattō. Multiple studies have found it to have various anticoagulant properties.  Numerous anecdotal reports litter the internet of non-ME patients replacing the prescription Warfarin with Nattokinase with degrees of success. Some ME patients have also found Nattokinase to be beneficial. The dosage should not exceed the maximum amount of 4000 fibrin units.

 
Lumbrokinase is an enzyme that is sourced from a type of earthworm. Some patients take it to break down the fibrin implicated in hypercoagulation. Several ME patients have noted an improvement in symptoms after taking Lumbrokinase. Serrapeptase is a similar enzyme to Lumbrokinase.

 
 

Conclusion

The ME-Hypercoagulation connection was a very promising theory until a small study with Fukuda criteria patients found no coagulation problems in CFS patients. The subsequent coagulation research in ME was then discontinued. Regardless of the validity of the hypercoagulation theory in ME, heparin has been an effective treatment for many patients. Those in the Berg studies experienced dramatic improvements and Dr. Teitelbaum’s comment that half of those ME patients with the most severe and difficult to treat symptoms “get better” with heparin provides hope. The double-edged sword with heparin is the potential side effects. This shifts the dynamics of the risk-reward ratio. If an ME patient is severely ill, with cold hands and feet and a low sedimentation rate, it may be worth getting subsequent and specialised coagulation testing done and discussing with their physician about whether heparin treatment is warranted.

 

Gabapentin (Neurontin) for ME

 
Gabapentin is an anticonvulsant drug primarily used to treat epilepsy that may be helpful to some ME patients.
 

Gabapentin may benefit ME patients due to:

• Reducing general pain
• Thwarting neuropathic pain
• Minimising fatigue
• Relieving muscle cramps
• Enhancing sleep quality
• Stopping restless legs syndrome
• Improving bladder function
• Having potential neuroprotective properties
• Decreasing multiple chemical sensitivity symptoms

 
It was originally thought that Gabapentin primarily worked due to its effects on the GABA neurotransmitter hence inducing calmness and sleep. It is now thought that Gabapentin’s mechanism of action is due to it being a calcium channel blocker. As a consequence, it may reduce the secretion of certain neurotransmitters that cause pain and stimulate the brain. Anecdotally, many ME patients have gained more energy as a consequence of taking Gabapentin. Unfortunately, in a reasonable portion of these cases, the effects seem to have gradually worn off.
 
 
ME specialists and doctors opinions’ on Gabapentin

Dr. Goldstein listed Gabepentin among his five most favoured treatments for those with ME. The others being; Nimodipine, oxytocin, intravenous lidocaine and baclofen. Dr. Goldstein believed that Gabapentin may regulate the neurotransmitter imbalance in the brains of ME and fibromyalgia patients. He recommended a low dose of 100mg-800mg, stating that effects should be noticed in the timeframe between 30 minutes and 8 hours. If tolerated, he would recommend the dose be slowly titrated upwards to a maximum dosage of 5000mg per day (e.g. 3 doses per day totalling 5000mg.) Dr. Goldstein found that a fairly high portion of his patients reported increased energy soon after their first dose with some patients also experiencing Gabapentin’s antidepressant effects.
 
Dr. Teitelbaum uses Gabapentin on some of his patients for sleep enhancement. He groups Gabapentin with Gabitril and Lyrica, stipulating that despite all three drugs being related, one of the three will often be effective and tolerated by the patient even if the other two are not. Dr. Teitelbaum generally starts patients on either Gabapentin or Gabitril and only prescribes them Lyrica if these drugs are not effective. He has found these three treatments to reduce pain levels, improve restless legs syndrome symptoms and improve the patient’s deep sleep. Dr. Teitelbaum warns that the aforementioned three drugs are not addictive but it is imperative that they be weaned off slowly especially if taken for a long period of time. He starts patients on 100-300mg per night of Gabapentin and gradually increments the dosage to 300-900mg three times per day.
 
Dr. Cheney categorises Gabapentin into the class of neuroprotective drugs that may help improve ME patients’ sensitivity to stimulation. He started those with ME on 300mg three times per day. He believes some doctors use doses of Gabapentin that are too high. In a 2009 talk, Dr. Cheney seemed to be less of an advocate of Gabapentin.
 
Dr. Enlander uses Gabapentin on some of this patients. He believes that Gabapentin stops the “abnormal impulses” ME and fibromyalgia patients’ brains experience. As a consequence, the brain’s muscle fibres experience a reduction in fatigue. Dr. Enlander uses doses up to a maximum of 2400mg per day
 
 
Studies

A 2007 study by Arnold et al. was performed on fibromyalgia patients who took Gabapentin at doses between 1200mg and 2400mg for a period of 12 weeks. Patients experienced significantly improved sleep as well as less pain and less fatigue compared to the placebo group. The most frequent side effects noted were sedation and dizziness.
 
A 2010 study by Usui et al. found a strong indicator concerning which fibromyalgia patients were likely to respond to Gabapentin. Those patients unlikely to respond to Gabapentin had hyperperfusion in certain parts of the brain as determined by a SPECT scan. Essentially, increased blood flow in the brain was strongly linked with a poor patient response to Gabapentin.
 
A 2015 study by North et al. examined the effects of an extended release version of Gabapentin on fibromyalgia patients over 15 weeks. Patients noted a reduction in pain, improved quality of life as well as an increase in quality and quantity of sleep. Many improvements were noted after only 4 weeks. Unlike the Arnold et al. study, this study had a smaller sample size and no control group.
 
 
Side Effects
Gabapentin is generally considered to be fairly safe and well tolerated. Despite this, some ME patients have anecdotally experienced side effects. A Cochrane Review by Moore et al. in 2011 based on data from chronic neuropathic pain patients concluded that Gabapentin was mostly tolerable however adverse events were frequent. 12% of patients withdrew from studies due to side effects. The most common being; dizziness, somnolence, peripheral oedema and gait disturbance. The Cochrane Review stipulated that serious adverse events were no more common in the Gabapentin group than the placebo group.
 
It should be emphasized that there is fairly universal agreement that Gabapentin should be started off at a lower dose and gradually increased if tolerated. Also stopping treatment suddenly may be harmful and patients are commonly advised to reduce the dosage slowly. Some doctors recommend Gabapentin only before bedtime with the motive of improving sleep whilst doctors with other objectives recommend that it be taken three times a day.
 
 
My Experience with Gabapentin

I began taking Gabapentin late in 2015, hopeful that I would reap several of its benefits. My poor sleep was the primary reason I chose to take Gabapentin. Related to this, I was interested to see whether my restless legs syndrome symptoms would ease. Gabapentin sometimes reduces patients’ overstimulation although I was slightly dubious as to whether this key symptom of mine would recede. I was also hopeful that I would join the anecdotal reports of ME patients who have gained more energy as a result of taking this drug.
 
I began taking 100mg of Gabapentin before bed and gradually increased this dosage as I failed to notice any side effects. I topped out my dosage at the relatively small maximum of 300mg per night. At this quantity I would sleep fairly deeply throughout the night but wake up still feeling unrefreshed. Curiously, my restless legs syndrome was unaffected by the Gabapentin. I was reluctant to increase the dosage any higher as I felt mildly ‘zonked’ throughout the days. Gabapentin’s effect of knocking me out during the night was a secondary reason to not increase the dosage further.
 
After 300mg per night of Gabapentin for a period of a month, its ability to keep me asleep during the night started to diminish. I then tapered off the drug with relative ease as its only real positive effect of keeping me asleep for most of the night had begun to wane. Several months later, I tried Gabapentin at an identical dosage and had a parallel experience. After one month, its sleep producing effects had diminished.
 
Overall, I didn’t notice any of the more common side effects of Gabapentin and its efficacy towards improving my general ME was negligible. Based on the Usui et al. study mentioned earlier, it was more likely that I would be in the responder group. My SPECT scan showed hypoperfusion (reduced bloodflow) in the brain- the opposite to the fibromyalgia patients who failed to respond to Gabapentin.
 
 
Conclusion

Gabapentin is a fairly common drug in the ME realm, although more regularly prescribed for fibromyalgia. It has the ability to target multiple, seemingly unrelated ME symptoms and thus patients take it for different reasons. My sleep length improved as a consequence of this drug but my sleep quality failed to be enhanced. Ultimately this single positive effect wore off causing me to stop taking the Gabapentin.

 

Astaxanthin, B1 Variants, Elimination Diet, IP-6, Naphazoline and Ranitidine

 

Over the past 12 months, I have tried many treatments that I haven’t written about in previous blog entries. This article will briefly touch on these treatments. Following this, I will detail how my health has played out throughout 2015.

 

2015 was a year that I trialled many ME treatments. These primary treatments were articulated in more detail in blog entries during the year. The following is a list of treatments I trialled at various stages of 2015 that I haven’t written about previously.

 

Astaxanthin

The main motive for me taking astaxanthin was its powerful anti-inflammatory effects. I have been experiencing joint pain during 2015 and I thought of astaxanthin as a safer long-term alternative to NSAIDs. One health questionnaire of 247 sufferers of back pain and rheumatoid arthritis or osteoarthritis found over 80% improving after taking astaxanthin. This supplement also has immunomodulatory effects and many other potential benefits.

 

 

I started taking 12mg of astaxanthin in November 2015 and plan to reduce the dose to 4mg within the coming weeks. The joint pain in my fingers, wrists and knees has all improved since I started taking the astaxanthin although I’m unsure if this is coincidental or not.

 

Benfotiamine and Allithiamine

During 2013, I took high dose thiamine (vitamin B1) and didn’t notice any effects. I wrote about this treatment in more detail here. In 2015, I trialled allithiamine and benfotiamine which are essentially different versions of thiamine. These two versions of thiamine may be better absorbed by the body than standard thiamine. Anecdotally, some patients have reported one of these versions to benefit them whilst standard high dose thiamine has not. I felt a bit sicker while taking 100mg of Allithiamine in combination with a mutli B supplement and I hence stopped this treatment after several days. I took 500mg of benfotiamine for about a month with no effects noted.

 

Elimination Diet

I have seldom written about diet on my blog for two primary reasons. The first is that food doesn’t seem to affect any of my symptoms. Secondly, I have tried omitting various types of food such as gluten, dairy products etc, at various times throughout my illness but have failed to notice any effects of these food omissions.

 

Fast forward to mid 2015 and I received an email from a fellow Australian ME patient who had similar symptoms to me and benefited remarkably from trying the elimination diet. I am grateful for their thoughts and must thank them for this. The elimination diet that I tried was devised by the Royal Prince Alfred Hospital with the premise of stopping food intolerances. Salicylates, amines, glutamate, gluten and food additives amongst other substances are avoided in the diet. These omissions ultimately don’t leave much to eat and following the strictest version of the diet was challenging to start with before I gradually adapted. I had a night of refreshing sleep while on the diet which is a once every two year rarity for me but other than that, I didn’t notice any other changes. I am planning to try the diet again in mid 2016 for a longer period of time.

 

There are various types of elimination diets and Dr. Cheney has written fondly of an elimination diet. He mentions, “Elimination diets, and improving digestion and gut epithelial function can pay huge dividends in this patient population.” Dr Cheney has found over half of his CFS patients studied to have food sensitivities. He believes an elimination diet is the best way to determine a patient’s food intolerances.

 

IP-6

The primary motive for me taking IP-6 was its ability to increase Natural Killer (NK) cell activity which is often impaired in ME patients. Dr. Edward Conley reports that he has used IP-6 to improve NK cell function in “dozens of cases” of CFIDS.  He elaborates on one case in which NK cell function improved 200% and the patient went from being unable to work to managing a 32-40 hour job.

 

I took IP-6 for a month during 2016 and didn’t notice any effects. The dose I was taking was 3.2 grams twice a day on an empty stomach. I didn’t have the ability to perform a natural killer cell function test to monitor its NK cell effects on me.

 

Naphazoline HCL

Dr Goldstein wrote prolifically about ME/CFS and his treatments always interest me as they seem divergent from many other ME specialists treatments, yet steeped in theoretical/practical evidence. He compiled a list of treatments he trialled often sequentially when a new ME/CFS patient visited him. This list is well worth reading and can be found here. Also listed are his musing on an assortment of other treatments. Naphazoline HCL 0.1% eye drops were the first treatment he tried on patients whom stepped into his office. If the patient benefited from this treatment, they would feel better immediately. Dr. Goldstein theorised that the trigeminal nerve would change the patient’s brain function as a result of these eye drops. It has been claimed that 20% of patients benefited from this treatment and on those patients whom they worked, the drops worked remarkably well.

 

It is imperative that the drops used are 0.1% not 0.01% drops. In some countries, the 0.1% drops are available over the counter. I tried the Naphazoline eye drops on two occasions during 2015 but didn’t notice any effects.

 

Ranitidine

Dr. Goldstein originally tried Ranitidine on infectious mononucleosis patients in the 1980s and due to the success he experienced began using it on ME patients. Ranitidine (Zantac) along with Cimetidine (Tagamet) are H2 receptor antagonists. Dr. Goldstein recommends the dosing structure of 150mg twice a day for one or two days. When patients do respond to one of these H2 receptor antagonists, Dr. Goldstein writes that the recovery is remarkable. He continues on to state that these drugs may cause overstimulation in ME/CFS patients.

 

 

An anecdotal report of a patient significantly improving after taking Ranitidine can be found here. This patient did however experience severe headaches as a consequence of the treatment which is a possible side effect. Ranitidine is available over the counter in many countries, if not, Cimetidine is normally available over the counter instead. I took 150mg of Ranitidine twice a day for three days but didn’t notice any effects.

 

My Health in 2015

 

Dust Allergy

The major improvement in my health last year was the reduction in nasal mucus discharge or mucus coughed up. This was my first ME symptom to emerge and for many years I was using two boxes of tissues a day. A few years ago, I had an allergy test and was put on dust allergy drops plus the nasal spray Avamys. This improved my tissue usage to around one box a day. In 2015, my sister moved out of the house and I moved into her room with only the bare essentials cluttering the room. This further reduced my dust allergy and I am currently down to using one box of tissues per week- a far cry from the 14 boxes a week I was using for 6 years!

 

Joint Pain

During mid 2015, my big toe joints began to experience pain, make cracking sounds and generally feel uncomfortable. My ankle joints also felt a similar sensation. In October, my finger, wrist, knee and neck joints also became painful. I began taking Astaxanthin, which I wrote about at the top of this blog entry. My newly developed finger, wrist, knee and neck pain improved however my toe and ankle pain persisted. I was referred to a rheumatologist who thought I may have osteoarthritis or rheumatoid arthritis however was unsure. He prescribed me painkillers and thought he would have a more clear idea of what’s going on after my symptoms had more time to progress. I see the rheumatologist again in March. Joint pain is often included on criteria lists for ME/CFS so it may simply be secondary to my illness.

 

 

I wrote a blog entry many years ago about the strange, permanent and dark spots that emerged on my joints when my illness initiated. This blog entry, found here, shows photos of the spots on my toes and fingers. I have over the past 12 months noticed a darkening of the big toe spots as well as the development of spots on the joint located at the base of my big toe. I’m unsure if this is related to the joint pain I’ve been experiencing. Also, further spots have appeared on my index and middle finger joints.

 

Sleep

2015 was the year that I struggled with sleep the most. Earlier in my illness, I would sleep right through the night and need an alarm clock to stop me sleeping for extended hours. This situation has inverted over the past handful of years and I now struggle to fall asleep. Also, when I wake during the night I am now often unable to get back to sleep. My Restless Legs Syndrome also prohibits my sleep.

 

Back Pain

The final significant health change that occurred to me in 2015 was my back pain. In late 2014 I suffered a thoracic back sprain by simply standing up from a sitting position. I have since experienced some quite irksome back problems. During 2015, I saw the physio every two weeks for the entirety of the year and took many painkillers for my back. I have been doing some very basic and modified stretches for my back too. I aggravated my back during August, September and October of 2015 by simply standing up from a sitting position and couldn’t really stand or walk properly on each of these occasions for a week. The rheumatologist whom I saw for my joint pain suspects that my back pain is related.

 

Conclusion

Overall, my ME health remained rather static in 2015. The peripheral symptoms I have written about above were nothing more than a blip on the radar when compared to how the crux of the ME has affected me. I am thankful that the mucus production symptom is being thwarted and I hope this continues into 2016. At present, the joint pain isn’t significant and I plan on continuing the Astaxanthin which may be easing it. My sleep and sleep treatments are something that I wrote about more extensively in my last blog entry and I have a sense of optimism that 2015 was an outlier as far as my insomnia was concerned. Regarding my back pain, I have found through trial and error that sleeping on the right type of mattress significantly improves this symptom. By finding the optimal mattress in 2016, this may not only ease the back pain but perhaps improve my sleep too. Improving my ME is a more difficult matter, although I have some more ideas up my sleeve for 2016!