People who have chronic fatigue syndrome (CFS) and Fibromyalgia (FM) often struggle with a kind of mental “fog”. We don’t understand why and there’s been little research on how to think more clearly. Mild Cognitive Impairment or MCI presents with a different kind of cognitive “fog” but it’s form might feel familiar. MCI affects some 15-20% of Americans, aged 65 and older. While anyone can develop MCI, the risk is higher among people who have a high blood level of the amino acid homocysteine. High homocysteine also predicts a higher risk for developing full-fledged Alzheimer’s Disease.
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.
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
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.
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.
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.
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.
Part 1 of 3:
Part 2 is coming soon!
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.
To view all of my videos, go to my YouTube Channel.