Connection Between Fibromyalgia and Restless Leg Syndrome (SQ-13)

A 2010 study published in the Journal of Clinical Sleep Medicine showed that adults with fibromyalgia (FM) are much more likely to have restless legs syndrome (RLS) than healthy people [1]. According to Nathaniel F. Watson, MD, one of the study authors, “Sleep disruption is common in fibromyalgia and often difficult to treat. It is apparent from our study that a substantial portion of sleep disruption in fibromyalgia is due to restless legs syndrome.” [2]

Another 2014 study published in the Journal of Back and Musculoskeletal Rehabilitation also points out that “Prevalence of RLS was found higher in Fibromyalgia Syndrome (FMS) than normal population and quality of sleep and quality of life were worse in patients with RLS.” [3]

Why are these findings important? Sleep disruption caused by RLS may aggravate fibromyalgia symptoms. In the light of this association, presence of RLS should be examined in every FM patient. Treating restless legs syndrome would improve some of the distressing fibromyalgia symptoms as well as improve the quality of sleep.

Both fibromyalgia and restless legs syndrome are linked with poor sleep. Fibromyalgia is a musculoskeletal condition characterized by widespread, unexplained muscle and joint pain accompanied by extreme fatigue and sleep disruption. Other common symptoms in people with fibromyalgia are morning stiffness, cognitive and memory issues, flu like symptoms, painful menstrual periods, headaches, tingling and numbness in hands and feet and irritable bowel syndrome [4]. And about 85 percent of fibromyalgia cases occur in women.

In contrast, restless legs syndrome (RLS) is a neurological disorder, where the sufferer experiences unpleasant, strange sensations in the leg often described as burning, aching, tugging or crawling – causing an irresistible urge to move the legs. The symptoms, ranging from minor to extremely painful, usually begin when you are sitting or lying down and tend to be most severe in the evening and night hours. Moving legs or getting up brings some temporary relief. RLS causes difficulty in falling asleep and interferes with restorative sleep as it may cause a person to wake up several times during the night due to leg discomfort. Without proper diagnosis and management, RLS can result in chronic sleep disruption followed by pronounced day time sleepiness, memory and cognitive problems and basically overall reduced quality of life.

The good news is restless legs syndrome can be managed, which will also improve the quality of life in fibromyalgia sufferers. The association between fibromyalgia and sleep is well-established. In fact, the combination of chronic widespread pain and inability to sleep is a two-fold setback for people with FM. While the chronic pain makes it difficult to sleep, the resulting exhaustion intensifies the pain. This cycle of sleep deprivation, fatigue and worsening pain continues, only serving to exacerbate FM symptoms.

On the other hand, healthy sleep can improve the pain symptoms, lifts up the mood and even breaks the vicious cycle leading to better sleep the next day. And that’s why addressing restless legs syndrome with proper treatment may hold the key to reduce fatigue and lessening the pain in people with fibromyalgia.

In conclusion, it is important to understand that there is treatment for restless legs syndrome, which will only help to alleviate fibromyalgia symptoms. The study also suggests that anti-depressants, commonly used to treat pain and depression in FM patients, are believed to induce restless leg syndrome. You may want to read some excellent sleep strategies by WebMD, here.

Fibromyalgia, Mitochondrial Dysfunction and Oxidative Stress

Fibromyalgia (FM) is a complex condition with no known causes. However, recent studies have demonstrated that mitochondrial dysfunction may have a role in the functional disorders observed in FM [5] [6]. In addition, mitochondrial dysfunction could be as a result of nutrient deficiencies, chemical exposure [7] or as a result of oxidative stress.

The results from a 2013 study led to the hypothesis that “inflammation could be a mitochondrial dysfunction-dependent event implicated in the pathophysiology of FM in several patients indicating mitochondria as a possible new therapeutic target.” [8]

A 2015 study published in Advances in Psychosomatic Medicine reports that “Chronic inflammation, together with raised levels of oxidative stress and mitochondrial dysfunction, has been increasingly associated with the manifestation of symptoms such as pain, fatigue, impaired memory, and depression, which largely characterise at least some patients suffering from Chronic Fatigue Syndrome and FM.” [9]

Before we understand what causes mitochondria to dysfunction, let’s get a quick rundown on how mitochondria functions and how our body generates the energy it needs to survive. Mitochondria are often referred to as the powerhouse of the cell. These tiny organelles supply energy that all living cells require to survive, reproduce and grow.

The mitochondria convert oxygen and nutrients into adenosine triphosphate (ATP), high energy molecules that store the energy required by our cells to carry out all their functions. This metabolic pathway, known as oxidative phosphorylation, requires oxygen and is the major source of energy produced in aerobic organisms, such as plants, animals and human beings. Brain and muscle cells, that require more energy for optimal functioning, contain thousands of mitochondria.

In this process of generating energy, also called aerobic respiration, mitochondria also produce volatile free radicals that cause oxidative damage to the mitochondria. While the body has an antioxidant-redox system in place, any imbalance in this equation causes more damage to the mitochondria. Our body responds by down-regulating the production of ATP to avoid any further oxidative stress, resulting in more fatigue.

In addition, glycolysis is another way our body produces energy. It is a primitive metabolic pathway that kicks in when we need energy at a faster rate than it can be delivered. Also called anaerobic respiration, this process uses sugar molecules and not oxygen to generate energy. It is quite an inefficient way of generating ATP molecules and also produces lactic acid as a by-product. This process comes in handy when we need to produce energy in an oxygen-poor environment.

For example, when we carry out any vigorous exercise, like jogging and running, our muscles need more energy. We begin to breathe faster as our lungs and heart attempt to shuttle more oxygen to our active muscles. However, we quickly reach a stage when our muscles demand more energy, surpassing our body’s ability to deliver oxygen to the working muscles. That’s when our body makes a switch from aerobic to anaerobic method of producing energy. This results in the accumulation of lactic acid, that dissociates into lactate and H+ ions, in the muscles, causing a painful, burning sensation in the muscles. When a normal, healthy person stops running, cells can easily switch back to the aerobic mode of respiration and the pain stops. However, in people with fibromyalgia, this switch is not easily achieved.

As explained by Dr. Sarah Myhill [10], “the sufferer can't make ATP quickly enough to shunt lactic acid back to acetate (via the Cori Cycle). Consequently, the sufferer is completely pole axed by ongoing lactic acid burn with inability to move and possibly secondary damage from lactic acid which, for example, is (unfortunately) good at breaking down the collagen matrix which holds cells together.

That is to say, the lactic acid may cause microscopic muscle tears, which would present as local areas of soreness and would trigger a process of healing and repair by the immune system. There would also be excessive release of free radicals as the immune system repairs. This may well cause further muscle damage in people with poor antioxidant system.”

Studies have shown that increased oxidative stress resulting in mitochondrial dysfunction (decreased production of ATP), is a highly observed event in FM sufferers. So, what causes mitochondria to fail? As it happens mitochondria need many important nutrients to function properly, for example magnesium, co-enzyme Q10, Vitamin B3 and acetyl L-carnitine. Lack of these nutrients – some of these also act as co-factors or substrate in the energy production process – may result in mitochondrial dysfunction. In addition, toxic stress due to chemical exposure, inflammation, poor diet, mental stress, poor anti-oxidant position, hormonal imbalance and long-term medications can also be easily blamed.

Can a good anti-oxidant profile help?

Does it mean that a good anti-oxidant profile can help nourish mitochondria and in turn improve painful symptoms experienced in FM syndrome?

A recent 2013 study investigated an exhaustive range of oxidative markers and found an imbalance between oxidants and antioxidants in FM patients, concluding that “the lower antioxidant enzyme activities may lead to oxidative stress through the oxidation of DNA and proteins, which may affect the health status of FM patients.” [11]

This research points out that treatment for fibromyalgia should focus on refurbishing the redox balance and reversing the oxidative stress that clearly damages energy generator mitochondria. Supplementing with vitamins, minerals and other anti-oxidants, such as Coq10, L-carnitine, Vitamin D, Vitamin B, Vitamin C, Magnesium and Glutathione may help achieve this, empowering mitochondria to produce more ATP, reducing free radical damage and improve the symptoms in FM patients.

References:

1. Viola-Saltzman M1, Watson NF, Bogart A, Goldberg J, Buchwald D. High prevalence of restless legs syndrome among patients with fibromyalgia: a controlled cross-sectional study. Journal of clinical Sleep Medicine: JCSM: official publication of the American academy of sleep medicine.. 2010 Oct 15;6(5):423-7.
2. High rate of restless legs syndrome found in adults with fibromyalgia. Science Daily: American Academy of Sleep Medicine. October 15, 2010
3. Civelek GM, Ciftkaya PO, Karatas M. Evaluation of restless legs syndrome in fibromyalgia syndrome: an analysis of quality of sleep and life. Journal of Back and Musculoskelet Rehabilitation. 2014;27(4):537-44. doi: 10.3233/BMR-140478.
4. What Is Fibromyalgia? Fast Facts: An Easy-to-Read Series of Publications for the Public. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. National Institutes of Health
5. Cordero MD, de Miguel M, Carmona-López , Bonal P, Campa F, Moreno-Fernández AM. Oxidative stress and mitochondrial dysfunction in fibromyalgia. Neuro Endocrinology Letters. 2010;31(2):169-73.
6. Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxidants and Redox Signaling. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. Epub 2013 May 29.
7. Sarah Myhill, Norman E Booth, and John McLaren-Howard. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. International Journal of Clinical and Experimental Medicines.
8. Cordero MD, Díaz-Parrado E, Carrión AM, Alfonsi S, Sánchez-Alcazar JA, Bullón P, Battino M, de Miguel M. Is inflammation a mitochondrial dysfunction-dependent event in fibromyalgia? Antioxidants and Redox Signal. 2013 Mar 1;18(7):800-7. doi: 10.1089/ars.2012.4892. Epub 2012 Nov 16.
9. Romano GF, Tomassi S, Russell A, Mondelli V, Pariante CM. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Advances in Psychosomatic Medicine. 2015;34:61-77. doi: 10.1159/000369085. Epub 2015 Mar 30.
10. Sarah Myhill. Fibromyalgia - possible causes and implications for treatment
11. Rubia M, Rus A, Molina F, Del Moral ML. Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status? Clinical and Experimental Rheumatology. 2013 Nov-Dec;31(6 Suppl 79):S121-7. Epub 2013 Dec 16.

Disclaimer

Information on our websites, in our blogs and our emails are provided for informational purposes only, and have not been evaluated by the EMA, EFSA or FDA. It is not meant to substitute medical advice provided by your healthcare professional and is not intended to diagnose, treat, cure, or prevent any disease. Our products are intended for adults, 18 years of age and older. While the vitamins and supplements mentioned here have been shown to have various health benefits, it is important to remember that supplements and dietary changes should be considered as part of an overall health plan and not as a substitute for professional medical treatment. Only a qualified healthcare practitioner can provide personalized advice and treatment plans based on your individual health needs and medical history, and you should seek advice from your healthcare professional before taking product(s) if you are pregnant or nursing.