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Is There a Connection Between MTHFR and Fibromyalgia?

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.


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.




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