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1. Preface

Fibromyalgia is a syndrome characterized by pain, fatigue, depression, sleep disturbances, anxiety and many other problematic symptoms. According to statistics, it afflicts approximately 2-5 percent of the human population and is more common in women than men.

chronic fatigueThe Medical community seems to see the syndrome in a somewhat narrow way. They usually recognize that the syndrome often begins after a stressful moment in life (e.g. an infection), and after that, the body stays in a chronic state of pain and fatigue. Because of
the common idea that fibromyalgia has no clear physiological causes, no targeted treatments exist, and the patients are often treated by various drugs such as antidepressants and anticonvulsants. (Bellato et al. 2012)

However, it isn’t acknowledged that fibromyalgia has some important features that might be very helpful when trying to understand the disease. My main idea is that most of the fibromyalgia symptoms are probably caused by disturbed energy metabolism – and therefore treatments that have positive effect on energy production might be very beneficial for fibromyalgia. The examples used in this article are thyroid hormones, CoQ10, and near-infrared.

2. Fibromyalgia and thyroid hormones

After becoming interested about the importance of thyroid function for health, I noticed that Dr. John C. Lowe had made important research showing that fibromyalgia and clinical hypothyroidism have dozens of biochemical and physiological similarities. Lowe and Yellin have written an excellent review article on this issue. (Lowe&Yellin 2008Øverbye 2007Garrison&Breeding 2003)

One of Lowe’s important findings is that fibromyalgia patients have 30% decreased basal metabolic rate on average. Similar extreme decreases in metabolic rate have also been noted in hypothyroidism and PCOS.  (Lowe et al. 2006Ursini et al. 2011Georgopoulos et al. 2009)

In his clinical trials, Lowe has noticed that supraphysiological doses of active thyroid hormone (T3) can be a very effective treatment for fibromyalgia, even in patients with normal thyroid hormone levels. Some patients seem to improve so much that they don’t even meet the diagnostic criteria of fibromyalgia anymore. In my opinion, it’s logical that a lot of good things should happen if you raise the extremely low metabolism to the normal level. (Lowe et al. 1996aLowe et al. 1996bLowe et al. 1997Lowe et al. 1998Friedman et al. 2006)

Lowe’s findings remind me of Broda Barnes, who thought that low thyroid function was a fundamental cause of many western diseases. In his popular 1976 book, he claimed that 40% of the American population suffered from thyroid insufficiency that is causing different diseases such as heart disease, migraine, acne, mental disturbances, menstrual irregularities, and fatigue. In my heart disease article, there are some scientific references about these issues.

Even though clinical hypothyroidism often isn’t the main cause of fibromyalgia or chronic fatigue syndrome (CFS), many of those patients do suffer from real thyroid problems. In a Swedish study, the researchers found that 40% of the CFS patients have inflammed thyroid glands, and many of these patients respond favorably to thyroxine treatment even if their TSH is within the reference range. Lowe has also noticed that 40% of the fibromyalgia patients have a central hypothyroidism – a thyroid inadequacy caused by pituitary malfunction. It seems that many of the doctors don’t seem to recognize these kinds of thyroid issues, so it’s usually important that the patient also looks carefully at his own blood tests. (Wikland et al. 2001Lowe et al. 2008Neeck&Riedel 1992Rettori et al. 1987)

I also have to mention that many of the fibromyalgia patients seem to have issues even with low doses of thyroid hormones (especially T3). Some of the patients also take low-dose hydrocortisone to tolerate thyroid hormones better, but I haven’t seen any research papers on that. I think that the doctors should be cautious when considering T3 treatments on their patients, because they don’t work well in every patient.

It seems that the idea of treating fibromyalgia with T3 is getting some popularity, since the issue is currently under research in Stanford University.

3. Fibromyalgia and CoQ10

During the last few years, a Spanish research group led by Mario D. Cordero has made important discoveries about the biochemical state of fibromyalgia patients. When they have investigated the patients’ white blood cells, they have noted dramatically decreased ATP levels, and extremely high levels of lipid peroxides (MDA).

Also, the intracellular levels of ubiquinone (coenzyme Q10 or CoQ10) were dramatically lower than in the healthy subjects. The interesting fact is that supplementation of CoQ10 reversed the above-mentioned biochemical abnormalities completely.

The supplement of CoQ10 (300mg/d) normalized the ATP and MDA levels, and decreased the fibromyalgia symptom scores very significantly from 59 to 30. The depression score has also been noted to decrease significantly from 22 to 6, while in the placebo group, the score increased to 24. (Cordero et al. 2012aAlcocer-Gómez et al. 2014)

cordero-coq10-fibro

 (source: Cordero et al. 2012a)

The research group has also investigated the effect of CoQ10 on other markers, and noticed that the supplement can decrease the expression of NLRP3 inflammasome and pro-inflammatory cytokines (IL-1β, TNF-α) and normalize the abnormal gene expression of fibromyalgia patients (IL-6, IL-8, AMPK, PGC-1a, SOD1, SOD2, NRF1). These same biomarkers are also importantly related to aging, so it could be said that fibromyalgia syndrome is functionally somewhat analogous to getting old. (Cordero et al. 2014aCordero et al. 2013aCordero et al. 2013bCordero et al. 2012bCordero et al. 2011Alcocer-Gómez et al. 2014)

Japanese researchers have been studying fibromyalgia of teenagers. They looked at plasma levels of CoQ10 and found that the levels were normal but the plasma levels of ubiquinol, the reduced form of CoQ10, were much lower than in healthy people. The researchers gave small amounts of supplemental ubiquinol (100mg/d) to the patients, and noted a slight reduction in the symptoms. (Miyamae et al. 2013)

The Spanish group of Mario Cordero has also noted that the plasma levels of CoQ10 aren’t decreased in fibromyalgia. Instead, they are often higher than in healthy subjects. I think this happens because of oxidative stress, which probably turns the reduced form ubiquinol compound into the oxidized form, CoQ10. But despite these increases in plasma levels, it seems that the CoQ10 levels inside the cells are generally decreased in fibromyalgia patients, and the CoQ10 supplementation seems to generally benefit the patients. (Cordero et al. 2009aMohr et al. 1992Yamamoto&Yamashita 1997)

“Given that many cell pathologies overlap between ME/CFS and inborn errors of
mitochondrial metabolism, we suggest that an inherited or acquired mitochondrial
dysfunction, which is perpetuated by exogenous or endogenous oxidative
stressors, is the driving force in the patients’ cell pathology. This results in
chronic fatiguing illness that may be alleviated by natural
mitochondrial enchancers such as CoQ10.”
 – Søes et al.  Coenzyme Q10 As a Modulator of Mitochondrial Dysfunction and
Maladaptive Stress Responses in Chronic Fatigue Syndrome (2015)

Low levels of CoQ10 in plasma has been noted in chronic fatigue syndrome, depression, migraine, and sepsis. Low levels of CoQ10 in cells has been noted in fibromyalgia, chronic fatigue syndrome, and periodontitis. Even though plasma level of CoQ10 isn’t a very good marker of CoQ10 status, it seems that in the diseases with low plasma CoQ10, the supplementation might be beneficial. There indeed is some evidence showing alleviation of migraine, periodontitis, and depression with a CoQ10 supplement. (Maes et al. 2009aMaes et al. 2009bHershey et al. 2007Donnino et al. 2011Castro-Marrero et al. 2013Bullon et al. 2011 & Sándor et al. 2005Wilkinson et al. 1975Prakash et al. 2010)

I don’t know what might be the main cause of CoQ10 deficiency and impaired energy metabolism in fibromyalgia patients. However, there are many studies showing that pathogens, alcohol, lipid peroxidation, nitric oxide, and pro-inflammatory cytokines (TNF-α, IL-1) can inhibit the cellular energy metabolism by many different mechanisms. Some of these factors have also been shown to deplete CoQ10. (Bullon et al. 2011Vidyashankar et al. 2012Donnino et al. 2011Forsmark-Andrée et al. 1997 & Morris&Maes 2014)

4. Fibromyalgia and near-infrared light

In my previous article, I argued that red light and near-infrared radiation increases cellular energy metabolism and ATP levels. This effect seems to be beneficial for many diseases.

So far it has been demonstrated that near-infrared might be one of the most potent medical treatments for some chronic diseases.

In two Brazilian studies, low level laser treatment (LLLT) with near-infrared was associated with a huge improvement in hypothyroid patients. Almost half of the patients (47%) could stop taking thyroxine during the follow-up period after the treatment. Good results have been noted for chronic diseases such as age-related macular degeneration, labial herpes, oral mucositis, and osteoarthritis. (Höfling et al. 2010Höfling et al. 2013)

In a couple of studies, LLLT treatment with near-infrared has been successfully used for fibromyalgia. (Gür et al. 2002aGür et al. 2002bArmagan et al. 2006Fernández García et al. 2011Ruaro et al. 2014)

It would be nice to know whether “low level laser” devices are needed at all. Sunlight, incandescent lamps, halogen lamps, and heat lamps also provide near-infrared, and theoretically they should have similar biological effects. In many animal trials, LED lamps have been as useful as lasers. There are also some trials showing large biological effects with halogen-based Bioptron lamps. (Zhevago&Samoilova 2006)

John Harvey Kellogg, in his 1910 book Light Therapeutics, argued that incandescent and arc lamps could be beneficially used for chronic fatigue (neurasthenia) and many other diseases such as diabetes, obesity, insomnia, and hair loss. Kellogg’s claims might sound big, but so are many of the recent study findings. The improvement of sleep was also recently demonstrated in a Chinese study in which they shone red light on the subjects’ skin. (Zhao et al. 2012)

5. Fibromyalgia, chronic fatigue syndrome, intestines and bacteria

Mark Pimentel’s research group demonstrated that about 100% of the fibromyalgia patients have small intestinal bacterial overgrowth (SIBO), which probably makes them susceptible to endotoxemia and many health problems related to inflammation and metabolic syndrome. In my previous article, I argued that endotoxemia and inflammation are fundamental factors causing metabolic syndrome. (Pimentel 2004)

In Michael Maes’ study, a diet designed to treat “leaky gut” seemingly decreased the endotoxemia of the patients, and it also decreased the symptom scores significantly. Some of the patients also received CoQ10, which probably accounts for some of the benefits, but I think that the improved intestinal function and decreased inflammation and oxidation must have been important factors as well. Antibiotics have also been shown to alleviate some of the fibromyalgia symptoms. (Maes&Leunis 2008Wallace&Hallegua 2004)

One research group reported that a gluten-free diet was very beneficial for a fraction of the fibromyalgia patients. None of these patients had celiac disease, but many of them had other symptoms of digestive system (heartburn, constipation, irritable bowel). I think that a gluten-free diet might be beneficial for some of the fibromyalgia patients, but I also think that there is a reason to suspect that the problems aren’t caused by gluten itself, but instead by some of the types of carbohydrates in grain products (FODMAPs). (Isasi et al. 2014Biesiekierski et al. 2013)

6. Additional ideas

Mitochondria: Disturbed energy-metabolism has also been noted in chronic fatigue syndrome (CFS), but some of the markers seem to be worse in fibromyalgia. (Myhill et al. 2009Castro-Marrero et al. 2013)

Mitochondrial biogenesis, AMPK and PGC-1α: Patients with fibromyalgia and CFS seem to have some disturbances with AMPK phosphorylation in various cell types (connective tissue, muscle cells, white blood cells). AMPK is quite important for cellular energy metabolism, so these problems might be importantly related to the metabolic problems of these diseases.

In the cells of healthy people, hydrogen peroxide exposure increases AMPK, PGC-1α and SOD activity, which can be seen as a marker of mitochondrial biogenesis and adaptation to oxidative stress. In fibromyalgia patients, this activation doesn’t seem to happen, and more cells die via apoptosis. However, Cordero’s group has noticed that ubiquinone (CoQ10) can normalize the AMPK/PGC-1α activity of fibromyalgia patients.

In animal experiments, endotoxin (LPS) has been shown to cause these problems related to mitochondrial biogenesis. (Brown et al. 2015Cordero et al. 2013aBullón et al. 2015aAlcocer-Gómez et al. 2015) 

Metformin, AMPK, pain sensitivity and fibromyalgia: In an animal study, the inhibition of AMPK phosphorylation alone increased the sensitivity to pain, but metformin prevented this harmful effect. In a recent case series, the use of low-dose metformin (200mg/d) was associated with significant improvement in biomarkers and symptoms of fibromyalgia patients. (Bullon et al. 2015b)

Metabolic rate and pain: Mark Starr, the author of Hypothyroidism Type 2: The Epidemic, has written that his pain patients’ basal metabolic rate averaged 15% below normal and natural thyroid hormone treatment often increased the metabolic rate and cured the pain. Thus, it seems likely that besides fibromyalgia, there are many other painful conditions that involve disturbed energy-metabolism.

Free fatty acids and energy metabolism: Young fibromyalgia patients in Japan seem to have extremely high levels of free fatty acids (NEFA), and it would be interesting to see if this applies to most of the adult patients as well. Because NEFAs seem to be able to inhibit some aspects of metabolism (Randle cycle, thyroid hormone receptors, insulin signalling), they might be one factor contributing to the syndrome. (Miyamae et al. 2013Fava et al. 2013)

A drug that lowers NEFA levels (acipimox) has been shown to increase insulin sensitivity and cellular ATP production, though some effects might be direct.

CFS patients don’t seem to generally have increased NEFA levels. (Miyamae et al. 2013Fava et al. 2013Gao et al. 2010Daniele et al. 2014Goodpaster&Coen 2014, van de Weijer T et al. 2015Stump et al. 2003Georgiades et al. 2003)

Insulin resistance and energy metabolism: Insulin resistance seems to be a potential factor causing disturbances of metabolism in cells. Even the descendants of diabetic patients have decreased muscle ATP production, even if there are no signs of inflammation. Diabetic patients have low hepatic ATP production. (Petersen et al. 2004, Schmid et al. 2011Szendroedi et al. 2007, Stump et al. 2003)

Glycine, histidine, taurine, cysteine: Amino acids glycine and histidine seem to have various beneficial health effects, at least in animal studies. They can improve NEFA oxidation and insulin resistance. Their consumption seems to decrease NEFA levels, inflammation, lipid peroxidation and other harms related to junk food and endotoxemia.

The combination of glycine and cysteine has led to remarkable improvements in the metabolism of elderly human subjects. (Nguyen et al. 2013El Hafidi et al. 2004, Feng et al. 2013, Nguyen et al. 2014Sekhar et al. 2011)

Since disturbed energy metabolism seems to be a crucial element in fibromyalgia, and it could be caused by factors such as NEFA and inflammation, it is tempting to speculate whether some anti-inflammatory amino acids could prove beneficial for this disease. (Morris&Maes 2014, Tastesen et al. 2014)

“[Glycine] users have anecdotally reported complete or almost complete resolution of fibromyalgia, asthma, psoriasis, arthritis, RSD and other manifestations of old, healed injuries which had caused chronic pain, as well as pain due to soreness after exercise or injury or gout flare-up.” – Joel Brind

Another interesting nutrient is taurine. Taurine levels seem to be decreased (by ~50%) in the blood of fibromyalgia patients. In animal studies, it has many protective effects on mitochondria, and in human studies, it has shown to be beneficial for patients suffering from chemotherapy, diabetes and heart failure.  (Bazzichi et al. 2009, Larson et al. 2007Moloney et al. 2010Hu et al. 2008, Franconi et al. 1995, Islambulchilar et al. 2015, Xiao et al. 2008)

Cholesterol levels: In some studies, the cholesterol levels of fibromyalgia patients have been higher than normal, but this association hasn’t been noted in other studies. Quite often, the level of basal metabolism is strongly correlated with the cholesterol levels (low metabolic rate -> high cholesterol). In adolescent Japanese fibromyalgia patients ubiquinol (reduced form of CoQ10) lowered their cholesterol levels significantly. Also, thyroid hormones and near-infrared have been shown to decrease cholesterol levels. (Cordero et al. 2014b, Miyamae et al. 2013, Ozgocmen&Ardicoglu 2000)

Oxidative stress: Fibromyalgia and CFS patients have higher levels of oxidative stress when compared to healthy controls. Oxidative stress is a common marker of eg. inflammatory diseases and major depression. (Ozgocmen et al. 2006, Manuel y Keenoy et al. 2001, Vecchiet et al. 2003, Shungu et al. 2012, Kennedy et al. 2005, Cell fatigue blog)

Leptin levels: Women with fibromyalgia have over two-fold leptin levels compared to the healthy controls. Even though leptin is mostly known as the “satiety hormone”, it also works as an inflammatory cytokine. Chronic inflammation can increase leptin levels. (Homann et al. 2014, Otero et al. 2005, Landman et al. 2003)

Gene expression: A recent study investigated the associations between the expression of some genes and fatigue diseases. The gene groups that were investigated, were associated with 1) purinergic signaling & cell signaling, 2) nerve growth & inflammation, 3) nociception & stress and 4) mitochondria & energy metabolism. Fibromyalgia wasn’t associated with altered gene expression, but CFS patients had altered expression of genes belonging to the groups 1 and 3. (Iacob et al. 2015)

Brain (in fibromyalgia): In fibromyalgia patients, decreased blood flow has been noted in some parts of brain, compared to healthy subjects (thalamus, nucleus caudatus, cerebral cortex). (Mountz et al. 1995)

Brain (in CFS): In CFS patients, decreased blood perfusion has been noted in their brainstem compared to healthy subjects. In one study, metabolism was also lower in brainstem and right mediofrontal cortex when compared to healthy subjects. (Costa et al. 1995, Tirelli et al. 1998)

Also, some studies have shown some evidence of decreased amount of white matter and atrophy of arcuate fasciculus. Some proof of neuroinflammation has also been noted in limbic system, brainstem and thalamus. (Zeineh et al. 2015, Nakatomi et al. 2014)

Nerves (fibromyalgia): According to one study, women suffering from fibromyalgia have some evidence of neuropathy in their eyes. (Ramirez et al. 2015)

Adrenal glands (CFS): In some studies, patients with CFS have had altered adrenal gland size and concentrations of some hormones (DHEA↓, DHEA-S↓, urinary cortisol↓). (Scott et al. 1999aScott et al. 1999b, Scott&Dinan 1998, Scott et al. 2000)

Mold exposure: According to one study, most of the CFS patients (93%) had mycotoxins in their urine. The researchers discussed that mycotoxins might be able to cause mitochondrial dysfunction, leading to disease. (Brewer et al. 2013a)

In their later article, the same researchers also speculated that chronically sick people might have mycotoxin-producing biofilms in their maxillary sinuses. (Brewer et al. 2013b)

Infections (mycoplasma): According to one study, most of the patients with fibromyalgia or CFS have mycoplasma infection (84%), but the existence of the infection wasn’t associated with the severity of the disease. Therefore, it might be irrelevant. (Nasralla et al. 1999)

Polyunsaturated fat, mitochondria and CoQ10: A Spanish research group has noticed that a diet high in polyunsaturated fatty acids (PUFA) can damage the mitochondrial DNA of rats, but low-dose CoQ10 supplementation can prevent the damage, increasing the lifespan of the animals by 12% (maximum lifespan by 25%). Other research groups haven’t noted similar lifespan increase, which might be related to lack of excessive PUFA or extremely high doses of CoQ10. (Ochoa et al. 2007Ochoa et al. 2005Quiles et al. 2010Quiles et al. 2006Quiles et al. 2005Quiles et al. 2004Huertas et al. 1999 & Sohal et al. 2006Lönnrot et al. 1998)

Amitriptyline: This drug (Triptyl) is a very popular antidepressant prescribed to fibromyalgia patients. Even though it has many beneficial effects, which might be related to the powerful inhibition of NLRP3 inflammasome, it also seems to have some harmful effects on energy metabolism. While CoQ10 doesn’t inhibit NLRP3 to the same extent, it doesn’t have the same harmful effects as amitriptyline, and it actually even protects from some harms caused by amitriptyline. (Cordero et al. 2014aAlcocer-Gómez et al. 2014Moreno-Fernández et al. 2012Bautista-Ferrufino et al. 2011Cordero et al. 2009b)

LDN: Low-dose naltrexone is another popular drug for fibromyalgia and CFS. I have heard some good anecdotes about it, but have no more information. (Younger&Mackey 2009Younger et al. 2013)

7. Conclusions

Fibromyalgia and chronic fatigue disease are both characterized by impaired energy-metabolism, which can be witnessed by measuring basal metabolic rate, ATP, or other mitochondrial markers. Sometimes a malfunction or inflammation of the thyroid or pituitary gland is involved in the pathology of the syndrome, but in most cases a clear hormonal cause cannot be found.

Treatments such as CoQ10, near-infrared and T3 have shown remarkable preliminary effects in the treatment of fibromyalgia, and the mechanism seems to be related to improvements in energy-metabolism. Treating endotoxemia and inflammation with an anti-inflammatory diet and supplements (glycine, taurine) might also be very important, because inflammation might be an important factor causing the energy-metabolism disturbances in these patients. (Morris&Maes 2014)

I hope that this article would bring some optimism to the miserable discussions regarding these difficult syndromes. There are so many people having huge difficulties in their lives because they are sick and fatigued, yet they are mostly offered painkillers or antidepressants because their problems aren’t understood in a logical light. Personally, I find it very fascinating that there actually is all this new evidence showing that maybe we can conquer these illnesses at some point – or maybe even today.

Further reading

180DegreeHealth – Thyroid, Inflammation, and Metabolic Syndrome: The Surprising Power of Context

Valtsu’s – Health Benefits of Glycine

Valtsu’s – The Therapeutic Effects of Red and Near-Infrared Light (long version)

Valtsu’s – Thyroid Hormones: The Ultimate Weapon Against Heart Disease?

Valtsu’s – Circadian rhythms

Chris Kresser – Is Fibromyalgia Caused By SIBO and Leaky Gut?

 

 About the author

Vladimir Heiskanen2Vladimir Heiskanen of Finland has been researching and writing about health for several years. Currently a dental student at the University of Helsinki and a blogger since 2010, he has a keen interest in human biology, and has studied scores of books, reports and cutting-edge health websites, especially the work of Chris Masterjohn, Paul Jaminet, Ray Peat and Matt Stone. You can read all of his fascinating articles published at 180D HERE.