MTHFR and Fibromyalgia

Chronic health issues such as fatigue, migraines, depression, cardiovascular disease, and fibromyalgia are now more common than ever. In some cases, these conditions can be related to nutritional status, psychological stress, genetic traits, or a combination of these factors. Most conditions are treated with medication or lifestyle intervention. 

In recent decades, connections have been made between the above conditions and specific genetic variants, namely the MTHFR gene. 

The methylenetetrahydrofolate reductase gene controls the enzyme that metabolizes folate and its biochemical pathway, methylation.

The methylation process occurs billions of times every second within cells and plays a crucial role in many bodily functions, including detoxification, energy production, and neurotransmitter production. Methylation is also involved in repairing DNA, regulating inflammation, and controlling levels of homocysteine - a harmful amino acid that can damage blood vessels and increase the risk of chronic inflammation.

Various studies indicate that a mutation on the MTHFR gene may play a part in the pathophysiology of fibromyalgia. 

This article will explain fibromyalgia and its symptoms as well as its etiology. We will discuss the possible links to MTHFR, particularly regarding research into its impact on glutathione and how those with fibromyalgia may find relief through supplementation with methylated folate. 

Fibromyalgia is a chronic condition characterized by chronic widespread musculoskeletal pain and tenderness without any obvious origins. It affects around 2% of the general population, mainly women. Although often compared to arthritis, fibromyalgia doesn’t cause joint or muscle inflammation or damage but soft tissue pain or myofascial pain.

Symptoms of fibromyalgia include: 

The specific cause of fibromyalgia is yet to be determined. Instead, it appears to be triggered or aggravated by a range of physical and emotional factors. These include psychological stressors, trauma, infections, bodily injury. 

For this reason, fibromyalgia is considered to stem from alterations in pain and sensory processing of the central nervous system. This seems to cause a disorder of pain regulation. 

Patients become hypersensitive to pain perception, which is often related to psychological issues. There is also evidence that fibromyalgia patients have elevated levels of excitatory neurotransmitters and reduced levels of serotonin, norepinephrine, and dopamine. This may contribute to the prolonged perception of pain. 

Anxiety and depression are commonly associated with fibromyalgia, and some studies suggest a major role in the stress response and neuroendocrine abnormalities.

Some studies have shown a genetic predisposition for fibromyalgia though there is no evidence of a definitive gene. However, fibromyalgia appears to be characterized by a hypomethylated DNA pattern, specifically in genes involved in the stress response, DNA repair, autonomic system response, and subcortical neuronal abnormalities. 

It has also been found that genetic variants and inheritance mechanisms in pain-related genes contribute to 50% in the development of chronic pain, which indicates a correlation between genetic variants and pain response.

Although classified as a rheumatic disease, fibromyalgia is treated more like a neurological problem than a rheumatic problem. The MTHFR connection partly explains this.

The strong association of genetic variants with chronic pain disorders has led researchers to conclude that pain-related gene polymorphisms are involved in the pathogenesis of fibromyalgia. 

The MTHFR polymorphism impairs the methylation process, which in turn impairs the production of numerous neurotransmitters, particularly those that affect mood, motivation, sleep, and pain regulation. 

MTHFR affects the body’s ability to create methylfolate. Methylfolate is essential for producing neurotransmitters such as serotonin, dopamine, and norepinephrine, which help regulate mood and pain perception.

Low serotonin has been linked to chronic pain disorders such as fibromyalgia. There is also a significant association between COMT (catecholaminergic enzyme) and regulation of serotonin. 

Studies have shown that single nucleotide polymorphisms identified in genes coding for neurotransmitters (such as serotonin and dopamine) may lead to the dysfunction of pain pathways in fibromyalgia patients. These polymorphisms are also identified in other symptoms seen in those patients, especially depression and anxiety.

It is also known that various mental disorders, especially depression, often accompany fibromyalgia. The MTHFR polymorphism is also associated with psychiatric disorders such as anxiety, bipolar disorder, and schizophrenia.

However, a Turkish study that investigated the link between the C677T gene polymorphism found it to be protective against fibromyalgia. The authors noted that further research would be required to explain this finding.

Gene polymorphisms have been related to a decreased pain threshold, higher levels of inflammation, and an increased susceptibility to disorders associated with chronic pain. Some of those genetic variants may trigger the onset of fibromyalgia.

MTHFR is also the most commonly identified gene in migraine, which is a known symptom of fibromyalgia. 

While there is some speculation about the link between MTHFR, fibromyalgia, and glutathione, evidence to support this theory is lacking. 

Serotonin may be the key to resolving many symptoms associated with MTHFR and/or fibromyalgia. 

Several studies have identified impairment in the serotonin pathway in fibromyalgia patients, which is also a significant effect of the MTHFR polymorphism. 

Serotonin is central to chronic pain disorders as it both inhibits and promotes pain perception by different physiological mechanisms. Studies of antidepressant administration in animal models of pain have shown the role of monoamines in pain modulation.

Methylfolate acts as an important regulator of cofactors involved in the synthesis of neurotransmitters, including serotonin. It is also required for the conversion of homocysteine to methionine, an amino acid that is converted to s-adenyl-methionine (SAMe). SAMe then serves as the methyl donor for all three monoamines serotonin, norepinephrine, and dopamine.

As an indirect regulator of serotonin, methylfolate supplementation has already been successfully used in the management of treatment-resistant depression. 

Improving levels of serotonin has helped to improve symptoms of depression, anxiety, insomnia, and somatic pains in a variety of patients. 

Some studies have investigated the benefits of supplementing with vitamin B12 and folate as a means to improve symptoms of chronic fatigue syndrome and fibromyalgia. Researchers have suggested that boosting serotonin may be a therapeutic mechanism for the treatment of fibromyalgia.

Addressing chronic pain such as fibromyalgia requires a multifaceted approach. While pharmaceutical drugs are most often used to manage pain, more recent modalities recognize the role of cognitive dysfunction in fibromyalgia. 

Self-management skills and cognitive behavioral approaches may be beneficial as a means of managing pain and associated disorders such as depression and anxiety.  

Supporting neurotransmitter production is also crucial. Studies have highlighted the importance of serotonin in the management of fibromyalgia and its benefits in modulating or alleviating the symptoms of pain, fatigue, and sleep disturbances.

Improving serotonin naturally is best done through supplementation of methylfolate. This is especially recommended if the patient also has an MTHFR polymorphism that inhibits their metabolism of folic acid. Methylfolate is an active form of folate that can bypass the MTHFR mutation. It is already in its metabolized form, which means it can be readily absorbed and utilized in the body for many biochemical reactions.

Some of the most highly recommended methylfolate supplements are in the Methyl-Life® product range. These are formulated especially for people with a heightened need for bioavailable folate due to MTHFR defects, dietary deficiencies, or other conditions in which nutritional absorption is impaired.