​Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complicated disorder.
​
It causes extreme fatigue that lasts for at least six months. Symptoms worsen with physical or mental activity but don't fully improve with rest.
​
The cause of ME/CFS is unknown, although there are many theories. Experts believe it might be triggered by a combination of factors.
​
There's no single test to confirm a diagnosis. You may need a variety of medical tests to rule out other health problems that have similar symptoms. Treatment for the condition focuses on easing symptoms.
Symptoms
Symptoms of ME/CFS can vary from person to person, and the severity of symptoms can fluctuate from day to day. In addition to fatigue, symptoms may include:
-
Extreme exhaustion after physical or mental exercise.
-
Problems with memory or thinking skills.
-
Dizziness that worsens with moving from lying down or sitting to standing.
-
Muscle or joint pain.
-
Unrefreshing sleep.
Some people with this condition have headaches, sore throats, and tender lymph nodes in the neck or armpits. People with the condition also may become extra sensitive to light, sound, smells, food and medicines. Source
In this video, Jan 4, 2025, I kick off walking through the info on this page. We didn't get too terribly far, as I spent the lion's share delving into the contribution of transdermal nicotine to helping with this health problem and others, and then I went on to talk about low-dose niacinamide for promoting cellular energy and beyond that to weight loss. Fascinating! Future progams will take us through the vast volume of information found on this page, so please stay tuned!
Here - Jan 18, 2025 - I continue through the page, highlighing l-carnitine, D-ribose, thiamine, riboflavin, niacinamide CoQ10, DHEA, pregnenolone, PQQ, beta glucan, and oxaloacetate. Mitochondrial energy dysfunction is clearly the not-so-wondrous root of ME/CFS/fibromyalgia. Tune in to learn more about how these various nutrients and hormones can be used to help bring recovery and restore health. For the rest of us, there is much benefit to including some of these in our daily health regimens for overall health and vitality.
The above page is a good resource with lots of detailed information. I highly recommend you go here to get an excellent overview of this condition before moving forward, examining what isn't working properly and what needs to be corrected - if possible - to return things to normal.
.png)
-
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, life-altering disease affecting many organ systems. It goes well beyond "being tired" and profoundly impacts patients' quality of life and abilities. Patients frequently experience a substantial impairment in physical and mental function at some point in their illness. It's estimated that as many as 3.3 million people in the United States have ME/CFS. The vast majority are undiagnosed.
-
ME/CFS is a biological illness, not a psychologic disorder. Patients are neither malingering nor seeking secondary gain. Patients have multiple pathophysiological changes that affect multiple organ systems. To date, none are sensitive or specific enough for diagnosis.
ME/CFS & the Thyroid
The overlap between thyroid fatigue and chronic fatigue syndrome symptoms is huge. In some people, thyroid disorder is at the center of their chronic fatigue. Addressing chronic fatigue syndrome in a person must include evaluation of thyroid hormone function.
There appears to be a problem with the way the body normally produces energy at the cellular level:
"Some people with ME/CFS may not efficiently produce or use energy from the usual "fuel" cells. These include oxygen, glucose, fatty acids, and amino acids. Exercise studies in adults show impaired oxygen consumption and activation of anaerobic metabolic pathways in the early exercise stages." Sourced from CDC paper above.
One would naturally think of the value of using those things that boost mitochondrial energy, such as CoQ10, l-carnitine/acetyl-l-carnitine, PQQ, niacinamide/NAD, etc.
My thoughts go immediately to l-carnitine, as it is excellent for increasing mitochondrial energy to the muscles, and acetyl-l-carnitine, as it is excellent for increasing mitochondrial energy to the brain. Both physical fatigue and cognitive issues are classic features of this problem.
However, high doses of l-carnitine can inhibit thyroid production of hormone, and with the combination of thyroid dysfunction and ME/CFS, one can feel hesitant about using it. I found this amazingly helpful paper addressing these concerns and delving deeply into what the science has to say about various forms of carnitine and ME/CFS: Mitochondrial Enhancers for ME/CFS and Fibromyalgia Pt II: L-carnitine and AcetylcarnitineI have confidently used l-carnitine in some of my hypothyroid clients, as studies have supported its use for relieving the fatigue of hypothyroidism. Apparently, according to the information in the above paper, the key is using a lower dose spread throughout the day. I thnk this could be huge. My approach would be to use both l-carnitine and acetyl-l-carntine to grab benefit for both the body and the brain. Depression is another classic feature of ME/CFS, and acetyl-l-carnitine is very helpful for depression: Acetyl-l-carnitine deficiency in patients with major depressive disorder
Omega-3's mentioned to work in synergy with l-carnitine and l-lysine to increase the body's natural production of l-carnitine. Lipoic acid also recommnended and oxaloacetic acid as possible enhancing cofactors. NAC - n-acetyl-cysteine, and there you have the glutathione factor.
"Glutathione (GSH) depletion and concomitant increase in O&NS and mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson’s disease, suggesting that depleted GSH is an integral part of these diseases."
Then this paper makes the case for MTHFR/folate metabolism problems resulting in the inablity to make adequate levels of glutathione. Therefore, supporting the entire methylation process is critical for improving ME/CFS: The Glutathione Protocol for Chronic Fatigue Syndrome
The Mitochondrial Enhancers for Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Series
I am intrigued by the idea of using niacinamide in low doses spread throughout the day based on this article:
People with ME/CFS/fibromyalgia (note, not everyone with chronic fatigue syndrome has fibromyalgia, but people with fibromyalgia do have chronic fatigue, and fibromyalgia is often seen in relation to ME/CFS) very often have difficulty with metabolism and losing weight. This is not surprising, given the problems with mitochondrial energy, as above, and using nutrients for fuel. Niacind and niacinamide are discussed at length here with regard to ME/CFS:
A Burning Question: Can Niacin Help Mitochondrial & Blood Vessel Issues in ME/CFS, FM and long COVID?
I favor the low-dose approach - approximately 50 mg (based on weight) - three times daily spread throughout the day, as detailed in the information on the "striking antiobesity effects" of low-dose niacinamide.
D-Ribose
By bringing purines and pyridimines together, D-Ribose provides the underpinnings for important substances such as DNA, RNA and ATP.
D-Ribose levels decline during the low oxygen states which may be present in ME/CFS and FM. When those conditions are present, cells turn to bringing two ADP molecules together to form ATP. The AMP left over is washed out – leaving the cell depleted in purines. Bob Naviaux found reduced purines in ME/CFS.
D-Ribose levels decline during the low oxygen states which may be present in ME/CFS and FM. When those conditions are present, cells turn to bringing two ADP molecules together to form ATP. The AMP left over is washed out – leaving the cell depleted in purines. Bob Naviaux found reduced purines in ME/CFS.
​
D-Ribose is able to enhance purine levels. Two non-placebo blinded studies from Dr. Teitelbaum suggest the D-Ribose may be helpful in a number of ways.
​
Several ME/CFS doctors recommend using 3 scoops of D-Ribose a day for several weeks and then dropping down.
CoQ10 (Ubiquinone/ubiquinol)
CoQ10 – arguably the most important mitochondrial enhancer, CoQ10 carries electrons from one part of the electron transport chain to the other, and it reduces oxidative stress. It’s used in a number of diseases.
Several studies have found low CoQ10 levels in ME/CFS and FM, and several trials suggest it could help.
CoQ10 comes in two forms: ubiquinone and ubiquinol. Ubiquinol is best absorbed and is recommended particularly as we age. It’s more expensive, but less is needed.
It may take up to a month for CoQ10 levels to plateau while taking ubiquinol 2-300 mg/day. It should be taken with fats. Be wary of taking it before bedtime.
Pyrroloquinoline Quinone (PQQ)
-
PQQ – is a mitochondrial generator, nerve cell protector, an anti-inflammatory, and is able to protect the mitochondria from oxidative stress.
-
PQQ may be able to improve short-term memory, attention and information processing.
-
PQQ may work better when taken with CoQ10. Doses appear to be around 10-20 mgs/day
Palmitoylethanolamide (PEA) – A Medical Food for Fibromyalgia (and ME/CFS?)
Another of my favorites! See my Palmitoylethanolamide (PEA) resource page.
PEA demonstrates a variety of properties in animal model studies that suggest it might be helpful in fibromyalgia and/or chronic fatigue syndrome (ME/CFS). Animal and laboratory studies suggest PEA has neuroprotective properties, can reduce glial (microglia and astrocyte) activation, inhibit astrocyte death (astrogliosis), and reduce inflammation by inhibiting histamine and TNF-a release in mast cells and by blocking cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) synthesis.
Yeast-Based Beta Glucan & ME/CFS
This research aimed to examine the potential alleviative effects of beta-glucan administration on fatigue, unrefreshing sleep, anxiety/depression symptoms and health-related quality of life in ME/CFS. A 36-week unicenter, randomized, double-blind, placebo-controlled trial was conducted in 65 ME/CFS patients, who were randomly allocated to one of two arms to receive four capsules each one of 250 mg beta-glucan, 3.75 µg vitamin D3, 1.05 mg vitamin B6, and 7.5 mg zinc (n = 35), or matching placebo including only microcrystalline cellulose as an excipient (n = 30) once daily.
​
The findings showed that the beta-glucan supplementation significantly improved cognitive fatigue (assessed with FIS-40 scores) after the 36-week treatment compared to the baseline (p = 0.0338). Taken together, this study presents the novel finding that yeast-derived beta-glucan may alleviate cognitive fatigue symptoms in ME/CFS. Thus, it offers valuable scientific insights into the potential use of yeast beta-glucan as a nutritional supplement and/or functional food to prevent or reduce cognitive dysfunction in patients with ME/CFS. Further interventions are warranted to validate these findings and also to delve deeper into the possible immunometabolic pathomechanisms of beta-glucans in ME/CFS.
I was recently reading and learning about the effects of nicotine on long-haul Covid symptoms. Nicotine is also very beneficial for other areas of health. It is non-addictive when used in transdermal form. The problem with cigarettes is the cigarettes themselves:
"It’s the quick hit that tobacco smoke provides, though, that makes nicotine so addicting."
Since my research led me to the understanding that nicotine locks into the nicotinic acetylcholine receptors - which are responsible for neuromodulation and cognitive processes, I thought about a possible value here for ME/CFS, since cognitive problems can be a very significant feature of this syndrome.
YES. I did find information relating to this!
It’s no surprise that we know a lot about nicotine. The tobacco plant – our main source of nicotine – comes from the Solanaceae family – which includes, alongside tomatoes, potatoes, eggplant, and peppers, psychoactive plants such as henbane (Hyoscyamus albus), belladonna or deadly nightshade (Atropa belladonna), jimson weed (Datura stramonium), and mandrake (Mandragora autumnalis). (Because tobacco can cause mild euphoria in some, it is also classified as a “psychoactive” plant.)
​
(It should be noted that nicotine does not cause the cancers caused by smoking or chewing tobacco; other parts of the plant do that.)
"Nicotine – what a strange thing! Nicotine patches are perhaps the most surprising entrant yet in the treatment sweepstakes for long COVID, chronic fatigue syndrome (ME/CFS), fibromyalgia, and related diseases."
Indeed, a close look at what nicotine patches do brings up the question of why they didn’t show up on the radar of ME/CFS/FM patients long before the coronavirus pandemic hit…"
“It’s fascinating to me frankly that one molecule found in nature can be so potent. It’s hard to imagine you could engineer a drug to do this.” Peter Attia MD
How might nicotine support the person with ME/CFS?
Feel-Good Enhancer
The fact that nicotine might make people feel better is no surprise given how many people smoked cigarettes/pipes before their dangers became apparent. By enhancing the activity of the nicotinic acetylcholine receptors (nAChRs) in the brain, nicotine increases several feel-good chemicals (mostly dopamine but also serotonin, GABA, endogenous opioids, and endorphins) that may be lacking in the brains of people with ME/CFS, FM and long COVID. Nicotine also triggers the release of acetylcholine and activates the sympathetic nervous system causing the release of epinephrine (and norepinephrine) – a stimulating neurotransmitter.
Immune Enhancer?
Immune enhancement is a total surprise, though. Nicotine also plays a key role in the cholinergic system – a system that presents fascinating possibilities for diseases like ME/CFS and fibromyalgia (FM) which feature an underactive parasympathetic nervous, or “rest and digest”, system.
The cholinergic system involves neurotransmitters (acetylcholine), receptors (AcHRs), and enzymes that activate the “cholinergic anti-inflammatory pathway“. With its direct link between the central nervous and immune systems, a dysregulated cholinergic system is believed to lead to inflammatory and autoimmune diseases. It turns out that nicotine enhances the productivity of this beaten-down system in ME/CFS/FM.
​
Brain-Fog Helper?
Nicotine may also help with some aspects of brain fog. A recent paper, “Nicotine’s effect on cognition, a friend or foe?”, reported that nicotine can enhance attention, and short-term and long-term memory – and nicotine has been used as a performance-enhancing drug. While warning of the dangers of smoking and high-dose nicotine use, the authors conclude that “nicotine-derived compounds could be a promising strategy to alleviate neurological disease-associated cognitive deficit“.
Indeed, an older meta-analysis of 41 double-blind, placebo-controlled studies found that nicotine or smoking “had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory”. A more recent meta-analysis of 33 studies featuring nicotine patches found that they “had statistically significant positive effects on attention” but non-significant effects on memory, in healthy non-smoking adults.
Studies suggest that the nicotinic receptors involved in the cholinergic immune response play a key role in neuroinflammatory diseases such as multiple sclerosis, Alzheimer’s, and Parkinson’s disease and nicotine has produced a variety of positive effects in a multiple sclerosis mouse model.
DHEA (dehyroepiandrosterone) and ME/CFS
Another of my favorites when it comes to the underlying features related to conditions of ill health, so, of course, I had to do some digging into what the science might say with regard to DHEA and people with this condition. I was not disappointed. (For much more information on DHEA, see my resource page HERE)
A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome
"Patients with chronic fatigue syndrome (CFS) frequently associate the disease onset with a period of high physical and/or emotional stress. Alterations in hypothalamic-pituitary adrenal axis (HPA) function have been demonstrated. Although Cortisol production in patients with CFS has proven to be low, Dehydroepiandrosterone (DHEA) production has not been measured. DHEA output may be altered in this population."
"Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p < 0.01), thinking (improved by 26%, p < 0.01), memory (improved by 17%, p < 0.05), and sexual problems (improved by 22%, p = 0.06) over the period of the trial. "
Abstract
The chronic fatigue syndrome (CFS) is a condition of unknown etiology, characterized by a persistent debilitating fatigue, the muscle-related symptoms and the neuropsychiatric symptoms. Recently, it has been reported that the patients with CFS might have impaired activation of the hypothalamic-pituitary-adrenal axis, and suggested that a part of the patho-genesis of CFS might be associated with abnormalities of the endocrine system. Herein, we show that the majority of Japanese patients with CFS had a serum dehydroepiandrosterone sulfate (DHEA-S) deficiency. Serum DHEA-S is one of the most abundantly produced hormones which is secreted from the adrenal glands, and its physiological function is thought to be a precursor of sex steroids. DHEA-S has recently been shown to have physiological properties, such as neurosteroids, which are associated with such psychophysiological phenomena as memory, stress, anxiety, sleep and depression. Therefore, the deficiency of DHEA-S might be related to the neuropsychiatric symptoms in patients with CFS.
Common Hormonal Problems in CFS - Adrenal
"Pregnenolone Steal"
"I think pregnenolone may be particularly pertinent in the treatment of chronic fatigue syndrome, and indeed the ageing process, for two reasons.
​
As described above, pregnenolone is the most upstream of all adrenal hormones and immediately downstream from cholesterol. The conversion of cholesterol to pregnenolone takes place in the mitochondria and so one can easily see how poor mitochondrial function could result in poor output of pregnenolone and, therefore, adrenal hormones.
​
Pregnenolone steal – if the body becomes stressed, for whatever reason, then the production of adrenal hormones is moved away from the anabolic building, healing and repair hormones to the catabolic stress hormones such as cortisol. In essence, when sufficiently stressed, pregnenlone is diverted away from making anabolic hormones to making catabolic hormones, essentially cortisol. Consequently, less hormone is available for healing and repair. People with chronic fatigue syndrome are permanently stressed by many factors, not least of which is their inability to live up to their potential. Hence CFS sufferers will likely suffer from pregneolone steal. This is bad news not only because this will mean that there is less hormone available for healing and repair but also because pregnenolone steal worsens the problems of low pregnenolone production in CFS sufferers, as already described above, resulting from their poor mitochondrial function.
Inositol - "Vitamin B8" - and ME/CFS
From the American Myalgic Encephalomyelitis and
Chronic Fatigue Syndrome Society
Inositol, like choline, is an important component of phospholipids, the fatty substances which surround all cells in the body. Also like choline, inositol helps with the transportation of fats, and prevents their accumulation in any one site (e.g., the liver). Because it is a key component of the myelin sheaths that surround nerves in the central nervous system, inositol performs a crucial role in maintaining the integrity of the nervous system.
Inositol also plays an important role in energy metabolism; its metabolites regulate bone mass and mediate amino acid signaling, acting as a “second messenger” for cell receptors. Inositol phosphates are important for a number of cellular functions, including cell growth, apoptosis (programmed cell death), cell migration, and cell differentiation. Inositol is found in the brain and nerves, muscles, bones, reproductive organs, stomach, kidney, spleen, liver and heart.
​
Because inositol is a second messenger of serotonin, it has been successfully used to treat several psychiatric conditions. (Second messengers are molecules that relay signals from neurotransmitters into the cell.) Medical uses of inositol include treatment of obsessive-compulsive disorder (OCD), anxiety, and depression. Inositol is also used for insomnia.
Inositol is produced in the gut in limited quantities by bacterial flora. Dietary sources include calf liver, cantaloupe, beans, dried beans, lentils, milk, nuts, oats, pork, rice, veal, wheat germ and whole-grain products.
Fibromyalgia - more to come!
