ME, Myalgic Encephalomyelitis, Chronic Fatigue Syndrome however it is currently labelled, and these are just a few names for the same condition, remains one of the most poorly understood medical conditions of our time. The month of May sees a couple of significant days to increase awareness of and funding for this devastating condition: the 12th is International ME Awareness Day and on the following Sunday we have Blue Sunday, a day when ME patients gather (mostly virtually) wearing something blue znd have a tea party.
To honour these days I’m writing this post to raise a little awareness about the condition I have lived with for nearly 20 years.
What is ME?
You may well ask, and it’s not a straight forward answer. The most common definitions describe a list of symptoms which include unexplained fatigue lasting more than six months, muscle pain, joint pain, brain fog, swollen glands, and many more. The key phrase here is “unexplained”, so other common causes of fatigue have to be ruled out. If you are now thinking that this sounds rather vague and general that is understandable. The one symptom that separates ME from more generalised fatigue is something called Post Exertional Malaise, which I will come back to in a moment.
For now let us talk about fatigue. In the 1990’s ME was renamed Chronic Fatigue Syndrome by a group of medical professionals who favoured a psychological explanation of the condition (I may write about this medical scandal at a later date), this model focussed more on fatigue. Fatigue is a common experience for many healthy people whether it is sleepless nights with young children, burnout from work, intense exercise and so on. The fatigue of ME is not like that, it is far more intense. At the milder end it can be relatively mild, patients are able to work but might not be able to do anything outside of that. However for those severely affected they are so depleted of energy that they are entirely bedbound and have to be tube fed. Unfortunately I am not being melodramatic when I say that ME can be and has been fatal, there is not enough energy to keep the bodies systems alive.
What Causes ME?
There really hasn’t been much research done into the causes of ME, so we really don’t have a clear idea. There are many theories but without the basic biomedical research that this all we have to go on. A common factor amongst ME patients is an initial infection, most commonly of a virus such as Glandular Fever (EBV), although this is not exclusive. The infection can be quite mild but the patient never truly recovers and is suffering fatigue and some or all of the symptoms listed above, six months later. Quite why an infection leads to ongoing symptoms even after no active agent can be detected is unclear..
Once of the most popular currently, with some data to support it, is that the mitochondria have become damaged in some way. Mitochondria are structures within a cell which are responsible for producing the bodies energy currency (ATP – Adenosine triphosphate), the end produce of the breakdown of glucose. ATP is then used by cells to do all the functions we need like nerve signals, metabolism, making new cells; in short there is not a process in the body with does not use ATP. This is one potential reason for why ME seems to affect so many disperate systems in the body.
The consequence for these damaged mitochondria is that for ME patients we cannot produce sufficient energy so to conserve the little energy we have the body starts downregulating or switching off systems, such as digestion. Thanks to the wonders of evolution the pathway used in the mitochondria is not the only mechanism by which ATP is produced. Many millions of years ago our simple cellular ancestors got cosy with a bacterium which was much more efficient at producing ATP, our ancestors were much better adapted to obtaining this bacterium’s preferred food source and so we entered into a symbiotic relationship. That bacterium is the mitochondria, and it still keeps a little piece of it’s DNA. Therefore, when the mitochondria are damaged and producing energy at a slower rate than its being expended the cells can use that older (and much less efficient) pathway to produce ATP. Unfortunately it is both more inefficient and slower, so ME patients can “Crash”, or have insufficient energy for their needs.
A ME “Crash” and Post Exertional Malaise
The term Crash is used to describe what happens when we have spent more energy than we have available, and it can feel like running headlong into a wall. You have no option but to rest and wait and hope that your body recovers in time. Crashes can last from days to weeks, months or even years. If a crash is particularly severe then it can result in a permanent loss of function.
It would be extremely useful for a crash to happen immediately the moment you have spent too much energy, but that isn’t how it works. One observation I have made about the anatomy of my own periodic crashes is that it is very difficult to spot when you are using too much energy. I believe, but have no data to back this up so it is just an opinion, that when my energy reserves start getting low it triggers a fight-or-flight response. In other words, continuing to use energy I don’t have is perceived by my body as a survival threat and it releases adrenaline to assist and get me out of danger. It is sad to report that the “danger” might just be having a friend drop round or in cases of those very severely affected being subjected to light or sound.
If you have been paying attention then you might have spotted a seeming contradiction in that last paragraph. How can you spend more energy than you have without dying. Apologies here comes a bit more biochemistry. When ATP is used by the body the energy is stored in chemical bonds, so to release the energy required a bond has to be broken, one of the tri-sulphide bonds. The resulting molecule is ADP (adenosine di-phosphate). ADP is usually returned to the mitochondria and converted back into ATP. Some scientists have speculated that it is this pathway which is damaged. If however we are continuing to use ATP up at a rate which is unsustainable then ADP is broken down further into AMP (adenosine mono-phosphate). The pathway to process AMP back into ATP is much slower, typically 24-48 hours.
For the sake of clarity let us imagine a marathon runner, they are using ATP at a high rate, but they have fully functioning mitochondria so the ATP is being recycled back into ADP. They will still be using energy faster than they can reconvert, but the marathon doesn’t last forever. By the end of the race they will naturally feel tired, which will last a day or two after the race and then they will be largely back to normal. This is because while they will almost certainly be having to wait for AMP to be reconverted back into ATP, their ADP to ATP conversion is also happening which provides sufficient energy for normal daily processes. The fatigue is felt when doing more energy intensive activities like climbing the stairs.
The difference between our marathon runner and an ME patient is that ADP to ATP process is damaged so there is not sufficient energy being recycled to manage daily processes, and thus more ADP has to be broken down into AMP. This is what causes a crash and the most important symptom of ME “Post Exertional Malaise”. This is when most, if not all, ME symptoms increase in severity. It typically starts in that 24-48 hour window after excessive exertion, but keep in mind that excessive for an ME patient can be very minor compared to healthy individuals. The crash will last as long as it takes for the ATP balance to be restored, or at least so this theory holds. The only way to achieve this is to cut all activity down to the absolute minimum, which can be challenging if you are already bedbound.
A clever video about ME/CFS created by @itsaliceella on Instagram.
Are there any treatments?
Short answer no, there is no recognised treatments for ME, see my previous comments about a lack of research. All we have is a management technique called Pacing. This broadly means trying to match your energy expenditure to what you have available, or preferably a less than that to built up reserves. It’s not an exact science and speaking personally I have struggled to assess how much energy I have available, much less how much I might be using. Various tools have been developed to try to make this easier such as using a heart rate monitor, looking at a metric called Heart Rate Variability (HRV) but it is still more art than science.
There are however a plethora of snake-oil salesman trying to take advantage of a patient population which is desperate. To date there are no treatments and no cures. The best we hope for is remission, but this is rarely a permanent state, especially for those who have had the condition for more than three years.
Is ME the same as Long Covid?
To make matters slightly confusing there are two separate variants of long covid. There are those patients who required hospital treatment for acute covid infections which resulted in organ damage, we are not talking about that cohort. For those patients who had a milder infection of covid and never recovered, then yes they probably by this point also meet the definition for ME. It seems that any viral infection has the capacity to cause ME, in the case of the covid pandemic it has been possible to tie it to a single origin cause. One of the few biomedical research projects currently in progress is to analyse the DNA of ME patients to see if there is a genetic factor in play. Of course had ME been properly researched Long Covid may be been avoided at least had proper treatments available.
Further Reading
The ME Association - The ME Association
MEpedia - an encyclopedia of all things ME/CFS