Powerful Proof that Symptoms of Chronic Fatigue Syndrome and Fibromyalgia are REAL and MAINLY PHYSICAL

I interviewed Dr. ALan Light, Ph. D by Skype in a three part video series. His research is among the very most innovative and important in the fields of chronic fatigue syndrome and Fibromyalgia. He, along with Lucinda Bateman, M.D. and colleagues from the University of Utah School of Medicine, has successfully conducted one study out of a very few that identify an objective laboratory marker which closely correlates with the patients’ “subjective” complaint of prolonged fatigue after modest exertion. This proves that the patients’ subjective reports of post-exertional malaise (PEM) are honest, real and based on physical events. More details on this study and its significance can be found on the following three 10-minute videos and text below.

Segment 1: Provides background on why and how this research was developed

Segment 2: Provides details about this critical study

Segment 3: Reactions from the scientific study and next steps

Details of Study

Dr. Light, Lucinda Bateman, M.D. and colleagues from the University of Utah School of Medicine measured output of messenger RNA output from 13 selected genes. They did this just before, shortly after, and for 48 hours following very modest exercise on a stationary bicycle. The subjects included 48 patients with CFS with or without co-occurring FM, 18 patients who had FM but not CFS, and 49 healthy controls. The 13 genes monitored related to sensory nerve signaling, cytokine and immune function and the sympathetic nervous system.

Results

All CFS and FM patients reported increased symptoms of pain or fatigue for a full 48 hours following the exercise. In controls, there was no reported fatigue and no significant change in gene expression. All subjects showed objective changes in the RNA output from key genes which also lasted a full 48 hours.

There were two distinct patterns of response: In 71% of patients with CFS moderate exercise increased messenger RNA output from 12 of the 13 genes. This was true whether or not they also had FM. Most of these genes related to inflammation or nerve signaling. In the other 29% of CFS patients, exercise caused a decrease in output of messenger RNA from an adrenalin related gene. Many of these patients also had a clinical history of orthostatic intolerance (low blood pressure with prolonged standing). In contrast, the FM-only patients showed no post exercise changes in gene expression.  Text on the full study and results can be found at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/full
Significance

By showing changes in gene output this objectively proves that the fatigue and pain are real and are mainly physical., Dr. Light’s work appears to identify two different subgroups of CFS patients—one where pro-inflammatory genes turn on, and a second type where blood pressure tends to fall and an adrenalin related gene turns down its activity.  Dr. Light’s work also suggests that Fibromyalgia can occur in two different forms—one that is closely associated with CFS and one which is not.

Encouraging News on Namenda (memantine) for Pain

namenda for fibromyalgia pain
Pain in a woman’s body

I previously posted an analysis of a double blind study where Namenda, a medicine for Alzheimer’s, showed benefit for fibromyalgia pain.   In the previous study from Spain, Namenda was significantly better than a placebo for treating Fibromyalgia. But only a minority of patients improved. As importantly, it took a six-month’s long trial of treatment before the benefit from Namenda compared to placebo was statistically significant.

After reviewing that data, I had mixed feelings about recommending memantine for my patients. (I will now call Namenda “memantine,” the generic version which is much less expensive.)   Since then I’ve recommended memantine to five FMS patients. In a bow to reality, I suggested they try memantine for a two-month trial period, instead of the six months used in the double-blind study. The results; two patients improved meaningfully. One could not tolerate raising the dose. Two followed through but memantine did not help.

Now I’m writing to alert you to an encouraging study where memantine helped a very different kind of pain, the chronic pain that can occur from a mastectomy among women treated for breast cancer. (There have been no further studies on memantine and fibro.)    After mastectomy, 30% or more of women develop a burning or shooting pain in the chest, arm and armpit that lasts for three months or more. In a single blind study, 20 women received memantine for two weeks before and two weeks after their mastectomy. Twenty other women who had a mastectomy took a placebo.

After three months, the women rated the intensity of their pain on a scale of zero to ten. The results: Women who had taken memantine experienced substantially less pain than did the women who took placebo. The p value was 0.017. (Less than .05 is “significant”.) Memantine also reduced the need for prescription pain medicines. Only one of 20 women who had taken memantine needed a prescription compared to six of 20 women who had taken placebo. (Six months post operation memantine patients still had less pain, but the difference was no longer statistically significant.)

Take-Home Thoughts
Memantine is probably useful for some forms of pain. But we should keep in mind it might react differently for different forms of pain. Post-mastectomy pain results from obvious trauma to peripheral nerves. FM reflects abnormalities in the brain and the spine that are not classically “traumatic.”   Since we have only one controlled study for memantine and fibromyalgia, anecdotal experience might be our next most useful resource.

Some scientists doubt that anecdotes are useful. As a practicing physician, I strongly disagree. Anecdotal experiences can and should influence our judgments—especially if we can create a mechanism through which many, many individuals can share their experience.    The Internet has become such a mechanism. Our challenge: how to adapt this mechanism to the practical needs of clinicians, researchers and patients who care about Fibromyalgia, Chronic Fatigue Syndrome and related health problems.

memantine-graph
memantine results for pain

 

Two key questions: Who has the skill and the interest to create a practically useful forum on line? Who has the interest and ability to organize and/or provide the necessary funding?

Please feel free to comment especially if you have taken memantine for any type of pain.

Flexeril for Fibromyalgia Pain, Sleep Problems and Daytime Fatigue

Background
Flexeril (cyclobenzaprine) is FDA approved for the short term relief of “muscle spasm associated with acute, painful muscoskeletal conditions.” It’s not approved for long term usage or to treat Fibromyalgia (FM).

flexeril for fibromyalgia pain
fibromyalgia and fatigue

Still, Fibromyalgia specialists sometimes prescribe Flexeril for use as a sleeping aid and to reduce Fibromyalgia pain. But at standard doses, Flexeril’s sedating effect often carries over to the next day, worsening fatigue. There may be a better way of prescribing Flexeril; not only a way that improves sleep and pain, but to actually lessen feelings of daytime fatigue also.

Continue reading Flexeril for Fibromyalgia Pain, Sleep Problems and Daytime Fatigue

A NEW Form of MAGNESIUM: Can it help Brain Fog and FM Pain?

Background

Cognitive function tends to declines as we age. For most people the decline is modest. This “semi-normal” decline is thought to be due to a decrease in the ability of cells to communicate with each other through connections called synapses. A similar defect is seen with Alzheimer’s disease.

Magnesium for fibromyalgia
Magnesium for fibromyalgia

Animal studies show that one way to increase the number and function of synapses is to raise the brain’s level of the mineral magnesium. When scientists increase brain magnesium in lab rats, the rats become smarter. They can think more rapidly and accurately than they did before.

But, most forms of oral magnesium don’t pass easily from the blood into the brain. An exception is a new form of magnesium developed by a research team from MIT specifically for the purpose of passing from the blood into the brain. This form is magnesium threonate,.  It is being developed by Neurocentria, Inc., a pharmaceutical company, under the brand name of MMFS-01.

The Study

Neurocentria’s team recently published a very important study. Their results strongly suggest that MMFS-01 can substantially improve mild cognitive function in aging humans.  MMFS-01 is not yet commercially available.  However, a “generic” magnesium threonate is available from the Life Extension Foundation under the brand name of Neuro-mag. Likely other “generics” are or will soon be available.

What is truly remarkable about the MMFS-01 study is that improvement in over-all cognitive function was seen within just six weeks. Improvement continued through 12 weeks, the full length of the study.  Subjects treated with placebo did not improve overall.

Volunteers for the Neurocentria study were age 50 to 70. All had test score evidence of mild cognitive impairment. Twenty five subjects took MMFS-01 and 26 took placebo. The treatment dose was between 1.5 and 2.0 grams per day in divided doses.  Four different cognitive tests were taken before treatment and again at six and twelve weeks. These tests measured executive function, working memory, attention and a concept called episodic memory.

Findings: With magnesium threonate executive function significantly improved compared to placebo at 6 and 12 weeks.  Working memory improved significantly at six weeks but at 12 weeks the placebo group had improved also. So, the difference for working memory was no longer statistically significant.  Attention improved in the MMFS-01 group compared to baseline, but this improvement was not statistically better than for those taking placebo.  Episodic memory improved with MMFS-01 by week 12, but was not significantly better than that seen with placebo.

However, when overall cognitive ability was calculated by combining results from the four tests, subjects taking MMFS-01 scored significantly better than subjects taking placebo. This was true at week 6 (P=.017) and at week 12 (p=.003).  As important, subjects taking MMFS-01 who had the greatest increase in red blood cell magnesium levels were alsomost likely to show major cognitive improvement. There were no major side effects.

Separate research suggests that magnesium might also help for fibromyalgia pain. This benefit might be because magnesium tends to inhibit the activity of NMDA receptors. Activation of NMDA receptors is believed to be one mechanism that creates fibromyalgia pain.  A recent open label study from Mayo Clinic found that transdermal magnesium chloride spray taken twice daily for 3 weeks was followed by a reduction in fibromyalgia pain.

Take Home Thoughts

Should physicians treating FM or ME-CFS “brain fog” by offer magnesium threonate as a potential treatment?  The arguments against: 1) We don’t know whether brain fog in fibromyalgia or ME-CFS has any relationship to the cognitive decline that is common with aging. 2)  We have only one clinical study to support the beneficial effects of magnesium threonate.

The argument for: 1) Brain fog is a major problem for our patients 2) We have no proven treatments 3)  For most (but not all patients), side effects from magnesium are minimal—mainly diarrhea if we get the dose up too high.

Should patients with FM or ME-CFS try magnesium threonate on their own?  I strongly recommend that all patients work with their doctor.  Certain patients should not take extra magnesium, especially those with any degree of kidney dysfunction.  Also, it would be useful to obtain a baseline red blood cell magnesium level and to monitor that level as treatment proceeds.

Since MMFS-01 is not available, using Life Extension’s or other generic equivalents is reasonable.  Of course, ideally, some angel would fund a proper controlled study. But, as usual, that’s not likely to happen anytime soon.

If any readers decide to work with their doctors and try magnesium threonate, I and other readers would be grateful to learn whether or not it helped. In the absence of research funding the best way for us to learn which treatments help will be for each of us to report our personal anecodatal experience along to each other.  We look forward to your comments.

Low Dose Naltrexone (LDN): Possibly a Major Breakthrough

Background

Naltrexone is an FDA approved medicine used to block the effects of opiate pain medicines such as codeine, oxycodone or OxyContin.  At its usual dose of 50 mg Naltrexone tends to increase sensations of pain because it also blocks the action of the body’s own natural opiate-like compounds. But at much lower doses, in the 3-4 mg range, LDN has long been used by alternative medicine-minded clinicians as a treatment for pain, fatigue and other symptoms. The key insight here is that very low doses of Naltrexone don’t harm our body’s natural opiates. Rather, at low doses, Naltrexone seems to act to reduce our sense of pain.

LDN and pain
LDN and pain

LDN helps a meaningful proportion of FM patients—perhaps 40%. And, its side effect profile has been relatively benign—almost certainly more favorable than our standard FM drugs. As importantly, LDN’s proposed mechanism, suppression of inflammatory chemicals (cytokines) within the central nervous system might lead toward a new approach for a broad range of diseases.

 

Study

double blind study was conducted by Jarred Younger PhD, and Sean Mackey, M.D., PhD  from the Stanford Medical School’s Division of Pain Management. Thirty one women with Fibromyalgia were each treated with 4.5 mg of naltrexone in the evening for 12 weeks and a placebo for 4 weeks.

Results

Reduction in pain scores compared to baseline were significantly greater during the LDN period compared to placebo. (28.8% reduction versus 18% reduction; P=0.016). LDN was also associated with improved general satisfaction (P=.045) and better mood (P=0.039). Thirty two percent of participants had an improvement in both pain and either fatigue or sleep while on naltrexone in contrast to an 11% response rate during placebo (P=0.05). The #1 “side effect” was increased dreaming, which some subjects felt were disturbing.

Other than a small pilot trial done earlier by the Stanford group, I believe that Younger and Mackey’s study is the only academically sound test of LDN for Fibromyalgia.  However, I and at least one other CFS-ME/Fibromyalgia specialist (Nancy Klimas, M.D, PhD personal communication) have found LDN useful. LDN is not a cure-all, but it seems to help a substantial proportion of patients. Dramatically exciting is LDN’s proposed mechanism, suppression of cytokines and brain immune cells called microglial cells. This brain-anti-inflammatory approach might also apply to other difficult to treat neurological conditions.

Fibromyalgia is known to have an element of central nervous system inflammation as do other brain related diseases including Multiple Sclerosis, Parkinson’s and Alzheimer’s.  Would LDN also help these conditions? Hopefully, more research will follow.

Take Home Thoughts

Low dose naltrexone helps relieve pain in a substantial proportion of people with Fibromyalgia. In some people it might also help with fatigue and mood, although that part has not been formally tested in studies.  Not all patients tolerate LDN but the most frequent side effects, increased dreaming and headache, are not dangerous and often decrease over time. Except for people who regularly take narcotics, it is reasonable to consider a trial of LDN.  For these reasons, clinicians who treat FM and/or CFS/ME should consider themselves obligated to learn more about LDN and, with informed consent, consider offering it to selected patients.