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Overview: General therapies for ME and CFS

 JUMP  | Immunomodulators | Low-dose Naltrexone | Vitamin B12 | Methylation | Nexavir | Supplements | Pharmaceuticals

This information was first compiled by Hip in Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment, with later modifications and additions by Shoutout about ME.

As well as specific pathogen-targeted therapies, there are many additional therapies, supplements and pharmaceuticals that can be helpful in chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME).

Nutritional supplements are an essential component of any ME and CFS treatment protocol. Research has shown that people with ME and CFS are routinely deficient in many important nutrients (notably zinc, magnesium, and carnitine).

These deficiencies, in and of themselves, can decrease the degree to which the body can absorb and make use of other nutrients. Even when there are no clinical nutritional deficiencies, the physiological demands of a chronic illness make it necessary to provide additional nutritional support – especially in light of the numerous GI problems prevalent in the CFS/ME population, which may lead to malabsorption.

In the supplements section of her comprehensive resource, CFS Treatment Guide, Erica Verrillo notes that some caution is advised when taking nutritional supplements.

As with pharmaceuticals, supplements should initially be taken in very small doses to test for sensitivity. Even if a supplement consists of something “natural” there is nothing natural about taking it in concentrated doses. Your body reacts to these as it would to any chemical. For that reason, it is wise to take supplements with food, unless instructed otherwise.


These are drugs and supplements that modulate (modify) the functioning of immune system. Some immunomodulators used in ME and CFS shift the immune response from the Th2 mode to the Th1 mode. There is evidence that ME and CFS patients are stuck in the Th2 mode, whereas they should really be in the Th1 mode, because it is the Th1 immune response that fights the viruses and intracellular bacteria linked to ME and CFS.1

These Th2 to Th1 shifting immunomodulator drugs and supplements include: inosine pranoxbex (Imunovir) and oxymatrine.1 2

Note that Th2 to Th1 shifting immunomodulators can make you feel worse for the first few months, but benefits accrue after that initial period. Dr Paul Cheney believes that the immunomodulator Imunovir will lose it’s effect if you do not “pulse” it. Pulsing means taking regular breaks Imunovir, using an on/off regimen such as taking Imunovir for 5 days, then stopping for 2 days.

Oxymatrine however should not be pulsed. Note that several ME/CFS doctors say that inosine is just as effective as Imunovir, but much cheaper (Imunovir is based on inosine).

(Ampligen) is a powerful but very expensive ($40,000 per year) immunomodulator drug that can lead to major improvements in ME and CFS. It has been shown efficacious in phase III clinical trials.1

Intravenous immunoglobulin (IVIG) has had mixed results, but can bring benefits (cost is around $25,000 for a course of treatment). More info here.

Rituximab (Rituxan) is an anti-autoimmunity drug which depletes B-cells in the blood, thereby reducing the autoantibodies made by B-cells which attack the body. A phase II clinical trial of rituximab for ME/CFS showed that around two-thirds of patients derived benefit, sometimes very major benefits.1 A phase III clinical trial is now underway.

Rituximab is very expensive, costing around $50,000 a year.

Low-dose naltrexone (LDN)

A low-dose naltrexone regimen (3 to 4.5 mg daily, taken before bed) can have positive effects for various autoimmune and neurodegenerative diseases, including multiple sclerosis, lupus, rheumatoid arthritis, Sjögren’s, Parkinson’s and Crohn’s. Many ME/CFS and fibromyalgia patients find LDN beneficial.1 LDN is cheap, costing $6 per month.

LDN has several metabolic effects: it blocks the mu-, delta- and kappa-opioid receptors briefly (which is thought to up-regulate endorphins), it increases levels of met-enkephalin and its receptor, blocks TLR-4 on microglia, and LDN is believed to increase natural killer cell function (NK function is often low in ME/CFS patients). More info: LDN for ME/CFS, LDN Overview.

Vitamin B12 injections or B12 sublingual tablets

Many ME/CFS patients find that high dose vitamin B12 substantially reduces their cognitive dysfunction (brain fog) symptoms. The recommended forms of vitamin B12 are: methylcobalamin or hydroxocobalamin.

One study found that ME/CFS patients taking methylcobalamin responded better than those taking hydroxocobalamin.1 Injectable vitamin B12 doses are around 1000 mcg three times a week; if taken sublingually instead, the dose is 5000 mcg daily. Improvements in symptoms usually appear after a few weeks of taking B12. Further reading: Rationale for using vitamin B12 in CFS, Methylation, B12, Glutathione, Chelation.

Methylation protocol

Dr Rich Van Konynenburg believed that insufficient methylation is a factor behind ME/CFS, and recommends boosting methylation using a supplement regimen based on the treatment program developed by Dr Amy Yasko for autism.

The methylation protocol involves taking the following supplements daily: vitamin B12 hydroxocobalamin 2000 mcg sublingual, L-5-MTHF 200 mcg, folinic acid 200 mcg, lecithin 1200 mg, and a multivitamin/multimineral tablet. Full details here: Revised Simplified Methylation Protocol (this is the last revision Rich made to his protocol before his untimely death in 2012).

Rich’s study on 30 ME/CFS patients found that 27% of them achieved major improvements from methylation after three months.1 Patients found it took an average of 5 to 6 weeks before the protocol started to work. Some patients find this protocol does not work until they switch to the methylcobalamin form of vitamin B12 rather than using the hydroxocobalamin form.

Prof Carl-Gerhard Gottfries of the Gottfries Clinic in Sweden observed that vitamin B12 plus folate helps around 20 to 50% of ME/CFS or fibromyalgia patients with the MTHFR mutation. ME/CFS practitioners in the US are observe similar results.

To properly validate this observation, the Open Medicine Institute are currently running a three-year placebo-controlled, double-blinded study on the efficacy of vitamin B12 plus folate for treating ME/CFS.1

The Health Diagnostics and Research Institute in New Jersey provide a test for methylation status, as do the European Laboratory of Nutrients (see their “amino acids analysis”). More info about methylation: Glutathione and the Methylation Cycle.

Nexavir injections

The injectable drug Nexavir (formerly Kutapressin) is an antiviral, an anti-inflammatory, and an immunomodulator that has demonstrated overall benefits for ME/CFS, and this drug is often employed by ME/CFS doctors, including Dr Cheney, Dr Enlander and Dr De Meirleir.

Nexavir treatment protocols vary, but in one study, ME/CFS patients were given one subcutaneous 2 ml injection of Nexavir for the first 25 days of treatment; thereafter one injection every two days, for the next 50 days; and thereafter one injection three times a week for the next 105 days.

This study reported a 42% remission rate in these patients at the end of this course of Nexavir treatment.1 Each injection costs around $10. A low preservative version of Nexavir called 4ME is used by Dr Kenny De Meirleir. 4ME is available here.

Dr De Meirleir reports that around 70% of his ME/CFS patients experience at least a 20 point increase on the Karnofsky scale as a consequence of taking Nexavir.1 Dr Enlander says that Nexavir helps about 30% of his ME/CFS patients, and when combined with other compounds including vitamin B12 and glutathione injections, Dr Enlander reports Nexavir helps 67% of his ME/CFS patients.1

Supplements beneficial for ME/CFS

Acetyl-L-carnitine improves mental fatigue in ME/CFS.1 L-carnitine helps ME/CFS.1 Omega 3 with omega 6 fatty acids (fish oil plus evening primrose oil) improve ME/CFS symptoms.1 VegEPA (EPA-rich essential fatty acids) produces ME/CFS symptom remission and structural brain changes.1 2

Magnesium (either applied transdermally on the skin, or given by injection) can be of benefit in ME/CFS.1 It has been shown to help with sleep and depression, as well as short-term memory and IQ.1

DHEA improves pain, fatigue, anxiety, memory and sexual problems in ME/CFS patients.1 NADH helps ME/CFS.1 Co-enzyme Q10 may increase energy in ME/CFS,1 and 150 mg of Q10 daily has been shown in a clinical trial to improve cognitive function and autonomic dysfunction in ME/CFS.1 Undenatured whey protein may help ME/CFS by boosting intracellular glutathione.1

Malic acid taken with magnesium can increase energy in ME/CFS and reduce pain in fibromyalgia.1 2 Pharmaton capsules (which comprise Panax ginseng and B vitamins) significantly improve fatigue in ME/CFS.1 Multi-vitamin and multi-mineral supplements may improve fatigue, sleep disorders, autonomic nervous system symptoms and headaches in ME/CFS.1

Vitamin D supplementation can result in a marked reduction in pain in fibromyalgia.1 Vit D may also help relieve depression by increasing levels of monoamines, such as serotonin, in the brain.1 2

Probiotics improve ME/CFS symptoms,1 and reduce anxiety symptoms in ME/CFS.1 D-ribose can significantly improve ME/CFS and fibromyalgia symptoms.1 Melatonin before bed improves fatigue, concentration and motivation in ME/CFS.1

Pharmaceuticals beneficial for ME/CFS

Low dose Hydrocortisone reduces fatigue.1 and improves Moclobemide improves brain fog.1 Very low dose amisulpride 50 mg daily reduces fatigue and somatic symptoms, and is well tolerated.1 Several ME/CFS doctors say clonazepam (Klonopin) helps reduce the unpleasant sensory overload problems of ME/CFS, improves sleep and treats anxiety;1 however 32% of patients had severe side effects when trying to stop this drug, although 36% experienced no negative effects when stopping.1

Several ME/CFS doctors find the anticonvulsant drug gabapentin (Neurontin), which is a GABA analog, helps reduce pain, reduces oversensitivity to stimuli, and enhances deep sleep; but on discontinuation this drug can cause significant withdrawal symptoms that can last for months.1

Dr David Bell found amantadine 25 mg to 50 mg daily helps ME/CFS, but says higher doses can exacerbate symptoms.1 Several ME/CFS doctors find the stimulant drug modafinil helpful for some ME/CFS patients.1


Additional information resources on ME/CFS therapies

More information about various ME/CFS therapies can be found at: Dr Jay Goldstein’s ME/CFS drug treatments, ME/CFS Immune System Treatments at Phoenix Rising, Dr Jacob Teitelbaum’s 30 Top Tips for Treating CFS, Dr MyHill Fatigue TreatmentsME/CFS Medications Database, Maija Haavisto’s free abridged ebook “Reviving the Broken Marionette” (lists ME/CFS drugs – full version here), Chronic Fatigue Syndrome Treatment – Wikipedia, MEpedia, Erica Verrillo’s Onward Through the Fog.

ME/CFS treatments are rated according to their user-rated effectiveness at Stories Out LoudCureTogether and the ME Association (see page 9).

FEATURE PHOTO: Tablet by kev-shine


Written by Russell Logan


Russell Logan worked as a magazine publisher and editor until forced into early retirement through ill health with ME. He has battled with moderate to severe ME for 25 years. He now lives in Noosaville, Australia.

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