A Functional Nutrition Approach to Fibromyalgia, Focusing on Mitochondrial Dysfunction

Fibromyalgia is a disorder characterized by widespread pain and tenderness in the muscles and bones, accompanied by fatigue, sleep, memory and mood issues. Fibromyalgia is most common in women, though it can occur in men. It most often starts in middle adulthood but can occur in the teen years and in old age.

According to Dr. Alex Vasquez, a renown functional medicine doctor, prescription medications are not the answers for getting to the root of what’s causing fibromyalgia or dealing with fibromyalgia symptoms.

Vasquez says research shows gut dysbiosis accounts for all the problems seen in fibromyalgia. He also says people with fibromyalgia have mitochondrial dysfunction, neuroinflammation, and pain – all which link to and stem from gut dysbiosis.

Dr. Alex Vasquez’s Pathophysiological Components of Fibromyalgia:

1. Dysbiosis (gut bacterial overgrowth aka: leaky gut and a high prevalence of SIBO). 

Studies show patients with fibromyalgia and complex regional pain syndrome have intestinal hyperpermeability (aka: leaky gut), which indicates a strong gastrointestinal component to the illness. See Dr. Vasquez's approach to fibromyalgia with a focus on dysbiosis and SIBO

2. Mitochondrial dysfunction (often caused by dysbiosis and SIBO)

3. Neuroinflammation and Central Sensitization (often caused by SIBO)

Central sensitization is a condition of the nervous system associated with an increase in pain and sensitivity caused by neuroinflammation. When central sensitization occurs, the nervous system goes through a process called wind-up and gets regulated in a persistent state of high reactivity. Both dysbiosis and mitochondrial dysfunction lead to and perpetuate neuroinflammation.

Function of A Healthy Mitochondria

Every living thing is made of cells, and mitochondria are found inside each and every one of those cells. Mitochondria produce about 90% of the energy cells need to survive, which is why mitochondria are often called “the powerhouses of the cell.” No energy = no life! Muscle cells need a lot of energy, so they have loads of mitochondria.

Aside from producing energy, mitochondria also break down waste products so they’re less harmful and recycle some of those waste products to save energy.

Mitochondria also have a special role in making cells die (apoptosis). As strange as this may sound, apoptosis is vital for the processes of growth and development. Sometimes cells don’t die when they should, and start to grow uncontrollably, and this is how a tumor starts to grow.

Dysbiosis and Mitochondrial Toxins

When there’s any interruption in the balance of gut microbes, it can lead to dysbiosis, which can cause mitochondrial impairment. How would that happen? The microbial toxins produced in the gut get absorbed and circulate through the body, including by the mitochondria, which damages them. Which toxins are responsible? Hydrogen Sulfide, D-lactate, and lipopolysaccharide. They are produced in the gut and are mitochondrial toxins.

It’s because of these microbial toxins that there’s a link between SIBO and fibromyalgia.

Hydrogen sulfide impairs gut motility and gut function, along with poisoning the brain and mitochondria, which is why those with fibromyalgia often complain of brain fog. You have to get that stuff out.

Lipopolysaccharide (LPS), a mitochondria toxin, stimulates proinflammatory cytokines, which are inflammatory markers associated with chronic pain. Since the gastrointestinal tract is the most abundant source of LPS, a person with SIBO and leaky gut increases systemic absorption of LPS and the overall consequence is inflammation and damage to the mitochondria.

In 2004, Pimentel et al showed that among 42 fibromyalgia patients, 100% of them showed laboratory evidence of SIBO, severity of which correlated positively with severity of fibromyalgia.

If you suspect you have leaky gut, here is The Institute for Functional Medicine’s 4R Program for Leaky Gut

Mitochondrial Dysfunction and Fibromyalgia

Your mitochondria are the energy-producing batteries of each and every cell, and improperly functioning mitochondria has been noted in people with fibromyalgia. It’s suspected to be triggered by gastrointestinal dysbiosis via LPS, D-lactate, hydrogen sulfide, and inflammation.

Mitochondrial dysfunction exacerbates and perpetuates microglial activation and glutaminergic neurotransmission, thereby promoting pain sensitization centrally while also contributing to muscle pain peripherally.

Treating mitochondrial dysfunction with ubiquinone (CoQ10) alleviates many biochemical and clinical manifestations of fibromyalgia (1).

Neuroinflammation and Central Sensitization

Central sensitization is pain hypersensitivity due to factors in the brain (and spinal cord). It’s a disproportionate sensitivity to pain because the brain is hyperactive/hyperresponsive.

The debate is: Is central sensitization primary or secondary?

Many doctors have been led to believe that the pain of fibromyalgia is due to primary central sensitization and the condition needs to be treated indefinitely with pain-relieving drugs. This idea and rationalization is very driven by, and often paid for, by the drug companies.

Vasquez says central sensitization is secondary to neuroinflammation. It’s not causing itself! No drugs necessary. This applies to migraines and fibromyalgia, but also to neurodegenerative diseases like Parkinson’s and Alzheimer’s.

Vasquez says neuroinflammation is an inflammatory response triggered by the microglia cells (the immune cells of the brain). When microglia are triggered, they produce an inflammatory response. Also, the amount of glutamate stops being managed, which allows too much glutamate in the brain. Glutamate is an excitatory neurotransmitter so too much is an excitotoxicity, which shows up as neurodegeneration, seizure, depression, anxiety, fatigue and central sensitization.

Get rid of what’s causing the neuroinflammation in the first place. In this case, it’s dysbiosis (gut microbial debris going from gut to blood to brain), stop triggering microglial cells, stop activating the cells that produce more glutamate. This causes the pain, fatigue and depression.

Vitamin D Deficiency and Fibromyalgia

Vitamin D deficiency is prevalent in chronic pain and fibromyalgia patients and promotes pain sensitization, myalgia and bone pain (osteomalacia). Vitamin D plays an important role in the gut, particularly when it comes to healing leaky gut. Since people with fibromyalgia have leaky gut, vitamin D is essential in making the gut less leaky. Sealing the gut means the body absorbs less microbial junk and debris, which is ultimately poisoning the mitochondria and brain.

Vitamin D also helps improve immune function through the production of anti-microbial peptides. It also has a systemic anti-inflammatory effect. Vitamin D makes the immune system more effective and more efficient (less inflammation but more immune accuracy). Vitamin D also improves magnesium absorption, which then improves mitochondrial function and reduce neuroinflammation so plenty of good reasons to use vitamin D.

Therapeutic Approach for Mitochondrial Dysfunction in Fibromyalgia

How do you approach mitochondrial dysfunction? You restore the foundation for health – this involves cleaning up the diet, consider incorporating intermittent fasting, a low carbohydrate diet, nutritional support (starting with CoQ10 and the additional supplements listed below), moderate exercise and sleep.

1. Paleo-Mediterranean Diet: fruits, vegetables, nuts, seeds, berries, high-quality protein; allergy avoidance.

2. Multivitamin/multimineral: use a high-potency supplement with nutrients in the most bioavailable form, especially the methylation B-vitamins (folate, not folic acid, and in the active form of 5 methyltetrahydrofolate), B6 (in active form of pyridoxal-5-phosphate (P5P) and B12 (in the active form of methylcobalamin).

3. Pyridoxine (Vitamin B6) to clear excess glutamate: up to 250 mg/day, possibly as high as 500 mg. choose the active form, pyridoxal-5-phosphate (P5P)

4. Vitamin D3: 2,000-4,000-10,000 IU/d to optimize serum levels

5. Combination fatty acid therapy: ALA, GLA, EPA, DHA, Oleic acid; these are taken specifically for neuroinflammation and to support the gut microbiome.

6. Probiotics: especially with allergies, IBS and/or antibiotics

7. CoQ10 (Ubiquinone): 300 mg/day is the proven dose, so at least start with that dose to get a clinical response, then taper down to 100 mg/day as needed. Start immediately!

8. Lipoic acid: 200-400 mg 3 times/day; Lipoic acid plays a role in mitochondrial performance because it’s responsible for shuttling pyruvate into the mitochondria (along with B-vitamins). Lipoic acid is an antioxidant, supports healthy and normal inflammatory levels, and inhibits viral replication. We get a lot of benefit from it.

9. Acetyl-Carnitine: 1-2 grams twice/day

10. Magnesium: 600 mg is the standard replacement dose; adjust per bowel tolerance; try different forms as needed. 

11. Exercise

12. Sleep/rest/relaxation

CoQ10 and Mitochondrial Dysfunction

The electron transport chain (ETC) is the last step of ATP production, and this is where most of the action in people with migraines and fibromyalgia takes place. Those with migraines and fibromyalgia do have some defects in the Krebs cycle, but the ETC is more important, and this is where CoQ10 plays a role. Most of the therapeutic benefit of CoQ10 comes from its ability to support the ETC. The ETC is made of 5 different proteins (complex 1, 2, 3, 4, 5). The 5th complex requires magnesium (phosphorylation of ADP to ATP), but complexes 1, 2, 3, which is the start and the bulk of the ETC, each requires CoQ10. It improves electron transport, which improves ATP production, and that reduces free radical formation, which do damage.   

When the mitochondria are impaired, they begin releasing their own mitochondrial DNA which promotes inflammation via multiple pathways. Giving CoQ10 reduces the inflammatory activity involved. Fatty acids (ie: DHA) are also part of the ETC.

Why Isn’t A Functional Approach Common Knowledge About Fibromyalgia Treatment?

Good research never grows old, but it does get buried by the constant avalanche of drug-funded infomercialized pseudoscience. Most current mainstream reviews are directly funded by drug companies. These days, the drug companies not only fund the research, but also pay the researchers to promote drug dependence and the idiopathic model; this is worse when they hide their drug company payments, with help of the journals. The journals are involved via advertising and paid re-writes. We’re talking millions of dollars per article!

Drug companies also fund medical schools, which pay the researchers, so lots of conflict of interest in research these days.

Drugs can be up to $600/month, and a typical patient might be on 2-3 of these drugs, which may not work better than a 50/50 chance. Get out of drug detention! Treat the disease by treating the cause of the problem. Most evidence points toward dysbiosis, mainly in the gut, and particularly SIBO. Treat the causes of the causes :)  It’s more effective, safer and certainly less expensive.

In Health and Happiness,

Kelly Harrington, MS, RDN

Registered Dietitian Nutritionist for Healthy Goods

 

References:

1. Vasquex, Alex, MD. Chronic pain, neuroinflammation, and central sensitization in migraine and fibromyalgia. Inflammation Mastery, 4th ed. Epic Functional Medicine Conference 2019 Houston. 

2. Cordero, MD et al. Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q10 effect on clinical improvement. PLoS One 7, 2012.

3. Wallace DJ, Hallegua DS. Fibromyalgia: the gastrointestinal link. Curr Pain Headache Rep. 2004 Oct;8(5):364-8. 

4. Chunqiu C et al. A randomized clinical trial of berberine hydrochloride in patients with diarrhea-predominant irritable bowel syndrome. Phytother. Res. 29:1822-1827 (2015)

5. Littlejohn, G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat. Rev. Rheumatol. 11, 639–648 (2015).

6. Von Känel, R., Müller-Hartmannsgruber, V., Kokinogenis, G. Egloff, N. Vitamin D and central hypersensitivity in patients with chronic pain. Pain Med. Volume 15, Issue 9, 1609–1618 (2014). 

7. Harris RE. Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis & Rheumatism. Vol. 60, No. 19, October 2009, pp 3146-3152.

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