Treatments

John Chia MD ( Torrance, California) has long maintained that he and his son contracted ME/CFS from an enterovirus infection. Enteroviruses (which include the coxsackie and polio viruses) usually cause flu-like symptoms in the Summer months (atypical for influenza, which occurs in the late Fall and Winter). At the last conference in 2009 Chia reported success treating himself, his son, as well as numerous patients who had stomach biopsies positive for enteroviral protein VP1. Treated subjects were given up to 600mg per day of oxymatrine for 3 to 6 months. 52% of the treated subjects improved on a 7-point scale (much better to unchanged to much worse), while only 6% of controls improved. In this year’s account, Chia reports an enhanced response when the antibiotic rifampin (300mg twice daily for 7 days) is given concurrently with oxymatrine. Of 48 subjects treated, 32 (67%) responded to such therapy. Two-thirds had a febrile response and transient worsening of symptoms, however, when rifampin was added. Oxymatrine (with or without rifampin) appears to be an effective therapy in a subset of PWCs with evidence of enteroviral infection in the gut.

[Ed. note:  Oxymatrine is a traditional herbal Chinese medication used for the treatment of viral hepatitis, viral myocarditis, some skin disorders, and even cancer. It is thought to inhibit the pro-inflammatory cytokines TNF-alpha and IL-6. It may also inhibit Substance P (a neurotransmitter partly responsible for fibropain) and antagonizes opioid receptors. Chia currently uses the Equilibrant brand, starting at 1 pill twice daily, then 2 twice daily, then 3 twice daily (available from equilibranthealth.com). The maintenance dose is 1 pill twice daily. Adverse effects include hyperkalemia or hypertension in 1% of cases, and 10% of subjects discontinued the herb due to intolerable side effects. Chia follows patient response by measuring coxsackie B3 antibody titers, TNF-α, and the IL-12/IL-10 ratio.]

An Ampligen update was provided by Dr. David Strayer (Hemispherx Biopharma Inc, Philadelphia), who reminded us that in previous studies 40 weeks of  Ampligen therapy improved exercise tolerance by 16.6% (compared to 4.8% on placebo) and reduced concurrent medication use by 72% (56% on placebo). In the current study, 208 Ampligen subjects were analyzed for antibody against XMRV. 33.7% of subjects were positive for XMRV. These subjects were sicker (as measured by activities of daily living and actigraphy). On treatment with Ampligen these same subjects demonstrated a 14% greater exercise response and 24% more reduction in medication use, compared to XMRV-negative subjects.

[Ed. note:  The generic name for Ampligen has now been designated as “rintatolimod” by the World Health Organization. Rintatolimod is considered a toll-like receptor agonist (TLR3 agonist). Although XMRV has been discredited by many, this study suggests that persons with antibody to XMRV are sicker than non-positive subjects, but respond better to rintatolimid treatment. Ampligen remains an experimental treatment for ME/CFS, and is available on a cost-recovery basis only at 4 centers in the USA, including the Hunter-Hopkins Center. Potential subjects must meet specific criteria and be approved.]

Fred Friedberg (University of NY/Stony Brook) exposed 68 persons with CFS (40%) or unexplained chronic fatigue (60%) to a Fatigue Self Management Course (n=21), usual medical care plus symptom monitoring (n=26), or usual medical care (n=21). The course involved two sessions with a nurse educator who discussed relaxation, pacing, cognitive coping strategies, walking, pleasant activities, and social support with the subjects. To make a long story short, the Fisk Fatigue Score and Patient Global Impression of Change both improved for those who received the self management course, which was attributed to education, better awareness, and behavioral or lifestyle changes in those who took the course. Those who did not improve generally experienced negative external stressors during the study, such as divorce or financial distress.

[Ed. note:  Education and understanding of the condition are stressed at the Hunter-Hopkins Center for just these reasons – patients do better when they are better informed. For those who seek more self help, I suggest taking the online course with Dr. Bruce Campbell (cfsselfhelp.org) or tackling the self-guided course produced by Drs. Lapp and Campbell at treatCFSFM.org.]

Two old friends, Richard Van Konynenburg and Norman Booth, presented posters again this year supporting their hypotheses.

Rich Van Konynenburg posits that gluthathione depletion causes a partial blockage of the metabolic methylation cycle, which in turn can explain many ME/CFS symptoms.  In 2009 he presented a treatment protocol, which he recommends again this year. Details can be found at aboutmecfs.org/Trt/TrtMethylStudy09.pdf, but in brief summary he recommends gently unblocking the methylation cycle by using 200 mcg of folate, 200 mcg of folate as folic acid and methyl-folate (Actifolate™, Metagenics Labs), a small amount of multivitamin, phosphatidyl serine 500mg, and hydroxycobalamin (oral B12) 2000 mcg. Konynenburg warns about using excessive amounts of these supplements.

Norman Booth once again presented Dr. Sarah Myhill’s hypothesis that mitochondrial function is blocked or failed in ME/CFS. An excellent summary of her work and recommendations can be found at drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure. In 2009 Dr. Booth explained a test of mitochondrial function that demonstrated decreased mitochondrial function in 70 of 71 PWCs, compared to a control group of 53 normal healthy subjects. The poster presentation this year focused on a therapeutic protocol consisting of pacing (rest periods and limit setting), a nutritious diet, nutritional supplements, and detoxification. All patients on the protocol moved up at least one point on the Bell Activity Scale (see drlapp.com/more-hhc/forms-and-patient-information, then click on “Adult Forms”), and some as much a 6 units. Booth and Myhill conclude that “whatever the cause of CFS/ME, mitochondrial dysfunction which can affect every cell in the body is a major factor.”

[Ed. note:  the diet mostly avoided dairy and gluten, but also limited sugar, caffeine, alcohol, aspartame, and MSG. Detoxification was accomplished by infrared sauna therapy. The supplements simply included a multivitamin, B12, vitamin D, CoQ10, and glutathione.]

GcMAF (pronounced “gee-see- MAFF”) is the newest fad in ME/CFS treatment. This compound is thought to activate macrophages that are not responding properly, whereby it is also known as Macrophage Activating Factor (MAF) derived from Vitamin D Binding Protein. GcMAF starts as an amino acid attached to three different sugars. B-lymphocytes cleave one sugar, and T-lymphocytes cleave the other, leaving just an amino acid – sugar complex. This complex (GcMAF) binds to dormant macrophages and activates them.

Macrophages are the “police” or “first responders” in our immune systems. When they contact “foreigners” such as viruses or bacteria, macrophages signal lymphocytes of the invasion, then gobble up the invader. Drs. Kenny DeMeirleir (Vrije University, Brussels BE) and Paul Cheney (Asheville NC) presented treatment papers featuring this compound, which has also been tried as an immune modulator in HIV and cancer.

DeMeirleir injected 0.25 to 1 ml weekly (subcu or intravenously) into adult subjects for up to 40 weeks. All were XMRV/MLV positive. He reported that 68/108 (63%) reported “noticeable improvement” in fatigue, sleep quality, pain, neurocognitive function, recovery time, orthostatic intolerance and digestive problems. Side effects occurred in 18%, mostly headache or sleep disturbance, and 7% dropped out due to these symptoms.

Cheney treated 21 patients for at least 2 months with sublingual GcMAF. 10/21 showed improvement in symptoms, and 5/21 failed to respond or got worse. Most subjects experienced exacerbation of their CFS symptoms, and two developed Vitamin D toxicity.

[Ed. note:  We are all seeking new treatments for ME/CFS but I don’t think this is it. These posters only described very modest improvement, numbers were small, and side effects were legion. I have now seen several patients who were involved in these studies and they report utter failure. At one time there was a voluntary website where subjects could report their results. When I checked the site, none reported any significant response, but the website has since been shut down.]

Tomohiro Sugino (Soiken Pharmaceuticals, Japan) offered that oxidative stress is very high in PWCs, so anti-oxidants are likely candidates for therapy. He treated 207 fatigued individuals (not ME/CFS) with imidazole dipeptides (carnosine and anserine derived from chicken breast), using 200mg or 400mg daily, compared to placebo. Fatigue (measured by Visual Analog Scale) was reportedly much improved at both doses, especially 400 mg daily. [Ed. note:  is this the next “5-Hour Energy” treatment?!]

EECP, or Enhanced External CounterPulsation, is a technique typically applied to persons with angina or congestive heart failure. Balloon-like leggings expand rapidly during the diastolic (relaxation) phase of the heart, pumping blood from the lower extremities to the heart. This increases cardiac output and improves coronary artery perfusion. Because stroke volume and cardiac output have been reported reduced in PWCs, Derek Enlander (NY, NY) treated 20 ME/CFS subjects without coronary artery disease with EECP for 7 weeks. There were no adverse events. There was a modest improvement in the patients’ overall well-being ( KPS from 56.2 + 8.3 to 62.1 + 9.6), while stroke volume and cardiac output did improve significantly.

[Ed. note:  I have had two patients who underwent EECP. One had cardiac disease, the other did not but did not meet criteria for ME/CFS either. Both reported remarkable improvement of their fatigue and other symptoms. Except that this technique is costly and time consuming, there might be benefit for selected patients.]

I have included one study in the treatment section that might fit as well into epidemiology. Irma Pinxterhuis (Oslo University Hospital, NO) entitled her poster, “What Can Be Done To Prevent Deterioration and Promote Occupational Performance.” Studying 15 severely affected women over time, Pinxterhuis aptly defined what helped and did not help. Improvement was affected negatively by lack of support and understanding, expectations or demands from themselves and others, and financial insecurity. What helped is worth emphasizing:

• Support of health care providers and others
• Social support
• Stress management
• Lowered expectations for themselves and from others
• Balanced nutrition and healthy or whole foods

Pinxterhuis wrote, “they needed above all peace of mind and a feeling that they and their family were taken care of, so that they could use all their energy on getting better.”

[Ed. note:  Who has worked with severely ill persons and not wondered, “What can be done?” I would add to the guidelines above:  Limited mental activity (reading, writing, computing, concentrating); very low activity levels, proceeding slowly (supine range of motion > range of motion with light resistance > very light aerobic activity); minimizing medications and supplements; and prescribing low doses of medication and increasing slowly.]