Many people will experience extended periods of fatigue during the course of their lives. Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS), however, involve more than just chronic tiredness and can strike both children and adults. In order to be diagnosed, a patient must meet all seven strict criteria (fatigue, post-exertional malaise, fatigue or pain, sleep dysfunction, pain, neurological/cognitive problems and two of the following: autonomic manifestations, neuroendocrine manifestations and immune manifestations). It is estimated that 2.5 to 5 per cent of the world’s population is affected, though reporting methods can be inconsistent. Regardless of whether the actual number falls on the low or high end of estimates, it’s still a staggering number of people. The two conditions are often used interchangeably or abbreviated together (ME/CFS), however there are differences between ME and CFS. ME literally means “pain in the muscles and inflammation in the brain and the spinal cord.” For the purposes of this post, I will be exploring the latest research around CFS specifically.
While a 1997 study found no correlation between MTHFR polymorphisms and CFS, a 2012 examination of 88 patients by Dr. Paul Anderson of Anderson Medical Specialty Associates in Seattle found a higher prevalence of these mutations among a group of CFS and fibromyalgia patients than in the normal population, particularly homozygous C677T and compound heterozygous C677T/A1298C defects. Treating these patients with a methylation protocol that included methylfolate, methylcobalamin (B12), folinic acid and a vitamin B complex that contained the active forms resulted in significant increases in positive patient outcomes compared to the standard naturopathic treatment protocol. Thus, testing and evaluation of ME/CFS patients for MTHFR gene mutations is crucial to obtaining the healthiest outcomes. To understand how methylation comes into play in the treatment of ME/CFS, we must look more closely at the condition itself.
The World Health Organization (WHO) classifies ME/CFS as a disease of the central nervous system. It seems, however, to be more complicated than that. Its symptoms are not only neurological but also involve the immune and endocrine systems, and are often triggered by infections, toxin exposure or physical trauma. It is potentially an autoimmune and inflammatory disorder, with patients presenting with “oxidative and nitrosative stress (O&NS), activation of immune-inflammatory pathways and mitochondrial dysfunctions with depleted levels of adenosine triphosphate (ATP) synthesis” and “autoimmune responses” in up to 60 per cent of cases. Patients may have reduced natural killer (NK) cell function and chronic or recurrent infections. Mycotoxins are present in the urine of a very high percentage of patients and low cortisol is also often a feature of the illness. Dr. Anderson identifies the following as primary issues with CFS patients:
– immune dysfunction – chronic infections
– gastrointestinal malabsorption and dysbiosis (and infections)
– mitochondrial disorder/dysfunction leading to poor energy modulation
– detoxification deficits
– sleep disorders
– hormonal dysregulation
As he explains:
Overwhelmingly, CFS has been identified as a symptom of mitochondrial failure. In Dr. Sarah Myhill’s popular handout “CFS – The Central Cause: Mitochondrial Failure,” she explains how mitochondria are the “engines” that power our cells. A lack of adenosine triphosphate (ATP), which is produced by the mitochondria, slows the cells and thus the body’s functions. As the body struggles to make energy it compensates by switching to anaerobic metabolism and makes ATP from glucose by converting it to lactic acid. The lactic acid builds up and causes muscle pain and heaviness in the body, leaving the person glucose deficient. She recommends rest, dietary changes and supplementation, including D-Ribose, CoQ10, Acetyl L-Carnitine, NAD, magnesium and B12 shots. Replacing lost ATP and glutathione are critical.
Referring back to Dr. Anderson’s paper we can see how improving methylation will help reduce the symptoms and improve outcomes for ME/CFS patients. Methylation controls the body’s sulfur metabolism, which is critical for sufferers. Slow methylation prevents the body’s immune and detoxification systems to work adequately, which is important for combatting infections and eliminating toxins. Diminished methylation reduces the synthesis of choline, creatine, carnitine, CoQ10 and some components of myelin. Methylation also determines the rate of glutathione synthesis. Glutathione depletion is endemic in ME/CFS patients.
I have an entire post coming up devoted to glutathione, which is the body’s critical antioxidant. According to ME/CFS expert Richard Van Konynenburg Ph.D., depletion of this ubiquitous tripeptide leads to oxidative stress, mitochondrial dysfunction, toxin buildup, immune dysfunction, herpes virus reactivation, thyroid problems and other dysregulation. People with methylation defects are often deficient in glutathione, which can inflame or cause many different diseases. Improving glutathione levels is vital to the recovery of many chronic illness sufferers, not just those with ME/CFS.
Other nutrients that have been found to be effective in the treatment of ME/CFS are vitamin D, calcium, DHEA, lysine, fish oil and good quality multivitamins. Acupuncture may be helpful in the alleviation of symptoms. ME/CFS patients can find assistance and dialogue with other patients on the Phoenix Rising forums, which focus on the condition. Finding a competent doctor will be crucial in the treatment of ME/CFS, should you suffer from it. And if you cannot tolerate methylated vitamins, don’t despair. As Dr. Anderson explains:
-ASSESS Sn/Sx and SNP’s
-Start LOW and work up
-TREAT the patient not just the SNP’s
-Treat from the OUTSIDE in
-Monitor SIGNS AND SYMPTOMS etc to adjust therapy
To find out more about Dr. Anderson’s seminars for training health professionals, click here.
In addition to MTHFR, a number of other gene polymorphisms (SNPs) have been reported in ME/CFS patients (you may refer to page 13 of this presentation by Dr. Van Konynenburg). In fact, my explanations in this post have been quite simplistic in order to give you merely a general overview of this condition. If you want to learn more I highly recommend watching this ME/CFS presentation by Dr. Van Konynenburg and reading through the two accompanying handouts (the PDF files linked to below the videos) on the web page. Please note that while the website is written in Swedish, be assured that both the video and the handouts are presented in English. Even those with methylation defects who don’t have ME/CFS will learn a lot from this presentation.
As a final note, it is important to be aware that CFS may be the diagnosis, albeit incorrectly, when a doctor really doesn’t know what is wrong with you. In one study, only around 23 per cent of participants were found to have unambiguous CFS. As there are no “markers” for CFS, a thorough doctor will look for other possibilities before settling on this diagnosis. Something to watch out for is chronic Lyme disease masquerading (not so subtly) as CFS. Lyme disease is the subject of another post because it is so prevalent and under-diagnosed these days. As this master symptom list indicates, the symptoms for CFS, fibromyalgia, chronic myofascial pain and chronic Lyme disease are almost identical. As this patient explains, the misdiagnosis often applies to a variety of diseases such as multiple sclerosis (which actually has a lot in common with ME/CFS), lupus and Alzheimer’s. So be sure and do the proper testing and rule out Lyme before you suffer needlessly for longer than you should. An evaluation of spinal fluid can actually tell the difference between CFS and Lyme, demonstrating that the two conditions are actually separate. Whatever your eventual diagnosis, improving methylation will assist with your recovery from all of these illnesses.
Do you suffer from ME or CFS? What are your recommendations?
Thank you thank you for posting the link that distinguishes the difference between ME &CFS. Ive been on this website reading everything I can for my friend and her son that got his mthfr results……. then saw this article and clicked it *since I have ME* Too often it is wrongly clumped together and I just had to say thank you for acknowledging the difference. *thats rare and i get sooooo mad when i see people not do that* Truly…. its appreciated.
Andrea Post author
My pleasure, Jes – I like to get things right!
Andrea, this is all new to me and very confusing. I’ve tried for years (since 1981) to figure out what my own problems could be, without much luck, or even being taken very seriously. Last year, my 41 year old son was sick with what was being treated as a respiratory infection. After 3 rounds of antibiotics and not getting well, he went back to the doctor and asked if they might be missing something. The doctor did an EKG and referred him to a Cardiologist. Because the first visit was going to be a consultation and he didn’t feel like he could make it, we convinced him to go to the ER. They admitted him to the hospital with an enlarged heart and clots in several different locations. Within a couple of days, he was transferred to a larger facility, in heart failure. To make a long story short, he’s had several balloon pumps, two LVADS that both clotted and after regaining a little heart function, was explanted. Within a couple of months he was put back in the hospital and is currently waiting for a heart transplant. In February of last year, I begged and pleaded with the team and especially hematology, to check him to see if there were any underlying issues. Finally, after the last balloon failed in the IABP, it had to be removed because it was clotted at the graft and a new one could not be inserted. He is currently without an assist pump and I had to beg them to keep him on Bivalirudin. While he was off anticoagulation, they finally did additional testing and found he is homozygous for MTHFR C677T. Why do some of the doctors on his team acknowledge this could be an issue and some just poo poo the idea? I think this could be a very big deal! If this is an underlying issue, wouldn’t a new heart suffer the same problems that caused the first one to fail? Help, please!
Andrea Post author
Hi Ms. A – my goodness! I am so sorry to hear about all that you and your son have been through. My personal assessment of the doctors is that MTHFR seems to be controversial. You speak to some who “poo poo” it as you’ve said, and others who do take it seriously. You are not alone in this – many, many people are finding the same attitudes in the course of their journeys to better health. I stand with the doctors and researchers who are taking it seriously – and there are many of those, just harder to find. I believe that as education and awareness around the importance of methylation pathways and MTHFR (and other important) gene mutations (SNPs) grows that more doctors will take it seriously. Often there are other factors at play – it would require more extensive testing.
I have not actually researched the issue of blood clots very extensively. What I recommend for you is to find a doctor who does take this seriously to assist you as you work with the other doctors. Hyperhomocysteinemia is not a new concept. Has your son’s homocysteine been checked? There are some doctor lists on the Resources page of this website. I wish your son a speedy recovery and that you have some success on your quest to find a doctor who can help you. I wrote an article about homocysteine a little while back. I’ll be launching a community in the coming weeks where you can chat with others about these issues. Good luck!
Andrea, you are brilliant. Thank you for these wonderful posts. I get overwhelmed with all the science, even when you write for unmedical peeps, but have so much gratitude for your work, and always gain insight as well as information to bring to my functional medicine docs. I look forward to your glutathione post too, and wanted to mention that I’ve done Ashok Gupta’s work for MCS – and his program was started for MC/CFS and his work is inspired too. If you and your readers are not familiar with his work, it’s called Amygdala Retraining. It’s really helped me with a lot of issues, symptoms, mood, negativity, thoughts, happiness, and joy. xo, Marcia from the-eco-nest.com
Andrea Post author
Thank you so much for your lovely comment, Marcia – I am so happy to help!
I assume you are talking about this program? http://www.guptaprogramme.com/
As I have no personal experience with it I can’t comment, but thank you so much for sharing your results here. So wonderful to hear that something has helped you!