Fibromyalgia/FMS

Fibromyalgia, also called fibromyalgia syndrome (FMS), or is a long-term condition that causes pain all over the body. As well as widespread pain, other symptoms of fibromyalgia include:

• increased sensitivity to pain
• muscle stiffness
• difficulty getting to sleep or staying asleep, which can make you feel very tired (fatigue)
• problems with mental processes (known as "fibro-fog"), such as difficulty concentrating or remembering things
• headaches
• irritable bowel syndrome (IBS)
• feelings of frustration, worry or low mood

Symptoms of fibromyalgia can sometimes suddenly improve or get worse.

Risk Factors

The cause of fibromyalgia is unknown. However, several risk factors, genetic and environmental, have been identified. Some environmental factors include stress, especially people who suffered medical trauma or abuse, gender (women), infectious illness, iron deficiency and metal-induced allergic inflammation. 

It has been suggested that genetics may play a major role in fibromyalgia and may explain up to 50% of the disease susceptibility. Here are some key genes that seem to be involved in Fibromyalgia:

Methylation

GSTM1 is one of the glutathione transferase genes. A specific SNP – and often the variation, in this case, is that the gene is absent or deleted, significantly impacts your ability to conjugate using glutathione, which can increase the toxic burden.

Dopamine

Research also suggests that dopamine is also involved in modulating pain perception and natural analgesia. FMS patients exhibit disrupted dopaminergic reactivity to painful stimuli. The DRD2 gene is a G-protein coupled receptor located on postsynaptic dopaminergic neurons that is centrally involved in reward-mediating pathways that control dopamine synthesis and release. Variants on DRD2 could alter its function and increase the risk of developing FMS. Carriers should ensure good intake of dietary protein and vitamins - PLP (B6), methyl-folate (B9) and methyl-cobalamin (B12) - sleep and regular exercise to support dopamine levels naturally.

ALPL is the main enzyme responsible for the clearance of pyridoxal-5-prime-phosphate (PLP) (vitamin B6), so variants on the gene influence the plasma levels of vitamin B6. As B6 is the main cofactor for GABA synthesis, which is the major inhibitory neurotransmitter in the brain, ALPL could play a role in FMS severity. Indeed, at a synapse level, GABA decreases a neuron's action potential or excitability. It is critical for relaxation, improves memory and mood, relieves anxiety, promotes sleep, moderates blood pressure, and influences catecholamine release and cytokine and hormone production. Disruption of GABA neurotransmission leads to many neurological diseases, including epilepsy and general anxiety disorder. Individuals with lower B6 status should ensure good sources of B6 - including organ meats, pork, chicken, tuna, salmon, chickpeas, sweet potatoes, hazelnuts and bananas.

A decreased GABRA2 receptor activity can lead to a reduced sensitivity to GABA. This genotype has been associated with increased risk of alcohol dependence as alcohol activates GABA receptors, promoting relaxation and reducing anxiety. By binding to GABRA2, the medicinal herb valerian activates GABA receptors and has similar sedative effects as alcohol, and can reduce the risk of dependence. L-theanine and rosemarinic acid (found in rosemary, lemon balm, sage, thyme and peppermint) can help support GABA levels by inhibiting its breakdown.

Cannabinoid/Pain System

Inflammation 

Inflammation has been suggested to have a role in the pathogenesis of FMS. Indeed, individuals with FMS tend to have higher levels of inflammatory cytokines (such as IL6), which can increase their sensitivity to pain as well as mood disorders. Interleukin 6 ( IL6) stimulates inflammatory and autoimmune processes. A genetic variant can lead to significantly increased activity. The Tumour necrosis factor (TNF) also helps regulate the immune response involved in inflammation, fever and the inhibition of tumour growth. Variants on TNF are associated with an overactive immune response and susceptibility to a range of inflammatory health conditions, including arthritis, asthma, migraine and Alzheimer's. It can up-regulate catabolic pathways and suppress protein synthesis in skeletal muscle, impacting physical performance.

Individuals suffering from high inflammation will want to ensure sufficient intake of anti-inflammatory nutrients such as omega-3 fatty acids in oily fish, like sardines, salmon and mackerel.

Antioxidants

Finally, oxidative stress due to the accumulation of Reactive Oxygen Species (ROS) in the mitochondria is also involved in the pathophysiology of FMS, as the cells of the central nervous system are highly vulnerable to the toxic effects of free radicals. Antioxidants, like superoxide dismutase ( SOD), catalase (CAT), and glutathione peroxidase (GPX), are enzymes of the defence system that work to prevent oxidative stress through the inactivation of ROS.

A variant on GPX1  confers a decreased breakdown of hydrogen peroxide and antioxidant activity. You can support GPX1 with selenium (brazil nuts) and glutathione (sulphur foods, melon). A genetic variant reduces CAT's activity and the breakdown of hydrogen peroxide, which can lead to increased free radicals. Support catalase with manganese - green vegetables, wholegrain bread and cereal. A slower SOD2 can lead to a slower breakdown of superoxide and increased free radical damage. Increasing the intake of manganese can also help to support SOD2 activity.

Lifecode Gx Reports 

All of the genes mentioned in this article are tested in the two following Lifecode Gx DNA Reports:

Nervous System Report - analyses gene variants that impact serotonin (contentment) and melatonin (sleep), dopamine (motivation), noradrenaline and adrenaline (fight or flight); glutamate (the major excitatory neurotransmitter); GABA (the major inhibitory neurotransmitter), which is critical for relaxation; and endoCannabinoids (AEA/ anandamide) which regulate other neurotransmitters. The report provides detailed recommendations for nutritional support to alleviate symptoms and optimise mental health.

Metabolics Report - presents the genes that can powerfully influence key pathways driving human metabolism - genes confer metabolic individuality and underpin energy regulation, longevity and healthspan. The results are relevant and easily formulate immediate diet and lifestyle protocols based on your genetic code.

Resources

Light KC, White AT, Tadler S, Iacob E, Light AR. Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome.  Pain Res Treat. 2012;2012:427869. doi:10.1155/2012/427869 (Paper about numerous genes involved in FMS)

Park DJ, Lee SS. New insights into the genetics of fibromyalgia.  Korean J Intern Med. 2017;32(6):984-995. doi:10.3904/kjim.2016.207 (Serotonin/Dopamine/GABA genes, COMT, BDNF)

D'Agnelli S, Arendt-Nielsen L, Gerra MC, et al. Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers.  Mol Pain. 2019;15:1744806918819944. doi:10.1177/1744806918819944 (TRPV, HTR2A, IL6, BDNF...)

Foerster BR, Petrou M, Edden RA, et al. Reduced insular γ-aminobutyric acid in fibromyalgia.  Arthritis Rheum. 2012;64(2):579-583. doi:10.1002/art.33339 (GABA in FMS)

Estévez-López F, Guerrero-González JM, Salazar-Tortosa D, et al. Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project.  Rheumatology (Oxford). 2022;61(8):3180-3191. doi:10.1093/rheumatology/keab911 (COMT, HTR2A, OPRM1...)

Qureshi AG, Jha SK, Iskander J, et al. Diagnostic Challenges and Management of Fibromyalgia.  Cureus. 2021;13(10):e18692. Published 2021 Oct 11. doi:10.7759/cureus.18692 (Numerous genes + IL6 & TNF)