The goal is to identify potentially useful but not yet completely proved treatments for Chronic Fatigue Syndrome, Fibromyalgia and other complex health problems. To subscribe, please enter your email address below.
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).
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.
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.
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.
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.
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 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.
A 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.
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.
This post is the final segment with Kim Jones, RN, PhD associate professor at the School of Nursing of the Oregon Health and Science University and one of the world’s leading experts on Fibromyalgia. The main goal of this 3-part series is to provide tips on how to exercise safely and effectively so that people with symptoms of Fibromyalgia (FM) or Chronic Fatigue Syndrome (CFS) can feel better. This segment includes valuable information on specific gym equipment and exercises and thoughts on the what to look for the right instructor and workout environment. If you have FM or CFS, feel free to post any personal experiences you may have from following the tips that are provided in this video.
This post is the second segment of three with Kim Jones, RN, PhD associate professor at the School of Nursing of the Oregon Health and Science University and one of the world’s leading experts on Fibromyalgia. The discussion continues from the first segment providing practical advise on how to successfully exercise with Fibromyalgia (FM) or Chronic Fatigue Syndrome (CFS). If you have FM or CFS, feel free to post any personal experiences you may have from following the tips that are provided in this video.
Part 2 of 3:
If you have not viewed Segment 1 yet, link to it here,
Part 3 is coming soon!
Exercise is the BEST REMEDY—but only if you do it not too much, not too little, but JUST RIGHT!
If you have Fibromyalgia (FM) or Chronic Fatigue Syndrome (CFS)—you know it’s not easy to do just right. This post is part of a three-part video series focusing on when and how to exercise. Our expert in the video, is Kim Jones, RN, PhD associate professor at the School of Nursing of the Oregon Health and Science University. Dr. Jones is one of the world’s leading experts on Fibromyalgia. She has published more than 50 research papers and worked closely on FM research with Robert Bennett, M.D., former chairman of the division of arthritis and rheumatology at the affiliated medical school. Dr. Jones also serves as President of the Fibromyalgia Information Foundation. Although Dr. Jones’ main focus is on Fibromyalgia, patients with Chronic Fatigue Syndrome should also benefit from her advice.
I had the pleasure of interviewing Dr. Ginevra Liptan, internist from Portland, Oregon. She is one of the nation’s leading experts on Fibromyalgia. As Oregon has a very active Medical Marijuana Program, Dr. Liptan is also an expert on how to apply medical marijuana to treat Fibromyalgia.
The first video from this interview addresses the positive and negative aspects of treating Fibromyalgia with medical marijuana.
As an aside, in New Jersey where I practice, persons who have Fibromyalgia and have not responded adequately to standard treatments will often qualify for the NJ Medical Marijuana Program. More information on this program and my direct experience can be found on my website.
The second video from this interview explains the practical do’s and don’ts of using medical marijuana for people enrolled in a medical marijuana treatment program.