Magnesium and Fibromyalgia: A Literature Review

Studies Exploring the Correlation Between Magnesium Levels and Fibromyalgia

Studies correlating magnesium levels (including those of the serum, erythrocyte, leukocyte, platelet, and hair levels) to fibromyalgia have shown varying results (Table 1).

Some studies showed decreased magnesium levels in several tissue compartments in fibromyalgia patients along with a negative correlation between magnesium levels and the clinical parameters of fibromyalgia.^24-27 Bagis el al²⁴ reported significantly lower serum and erythrocyte magnesium levels in patients with fibromyalgia compared to controls, along with a negative correlation between the magnesium levels and fibromyalgia symptoms. In Kasim’s²⁵ study, serum magnesium levels were significantly lower in patients with fibromyalgia when compared to normal healthy individuals. Kim et al²⁶ found that concentrations of magnesium in the hair of female patients with fibromyalgia are significantly lower than of controls, even after adjustment of potential confounding factors. Sendur et al²⁷ reported significantly decreased serum levels of magnesium by fibromyalgia groups along with a meaningful association between magnesium level and fatigue in fibromyalgia patients.

Several reports showed no difference in magnesium levels between fibromyalgia and control subjects, with no correlation between magnesium levels and fibromyalgia parameters.^28-31 Andretta et al^28,29 and Sakarya et al³⁰ found no significant differences in the serum levels of magnesium between fibromyalgia patients and control subjects.^28-30 One of the studies performed by Andretta et al,²⁸ showed no correlation between serum magnesium levels and pain, quality of life, and depression risk in the fibromyalgia group. Sakarya et al did not find significant correlations between the mean levels of serum magnesium and number of tender points, scores of visual analog scale (pain intensity measurement), Fibromyalgia Impact Questionnaire (functional status evaluation), and Beck Depression Inventory (depression level assessment) in fibromyalgia patients. The study of Prescott et al³¹ also showed no difference in red blood cell or plasma magnesium levels between fibromyalgia patients and controls.

Few investigators reported increased levels of magnesium in patients with fibromyalgia.^32,33 Bazzichi et al³² found significantly higher magnesium levels in the platelets of fibromyalgia patients compared to controls. Unlike Kim et al,²⁶ Ng reported significantly increased hair magnesium levels in fibromyalgia patients.³³

In some studies, different laboratory assays within the same study showed varying results of magnesium levels.^13,34 Eisinger et al³⁴ evaluated leukocyte, erythrocyte, and serum magnesium levels in fibromyalgia patients in comparison to controls. They reported significant increase in leukocyte magnesium level in fibromyalgia patients with slight non-significant decrease in erythrocyte magnesium level and no difference in serum magnesium level, compared to control subjects. Romano et al¹³ measured plasma and red blood cell magnesium levels in fibromyalgia patients and compared them with those of osteoarthritis control subjects. They found that fibromyalgia patients, compared to reference laboratory and osteoarthritis controls, had significantly lower red blood cell magnesium levels but no difference in plasma magnesium levels.

Studies Investigating the Effect of Magnesium on Clinical Parameters of Fibromyalgia

Bagis et al²⁴ investigated the effect of magnesium citrate treatment on fibromyalgia symptoms. The study included 60 premenopausal women diagnosed with fibromyalgia. The patients were divided into 3 groups. The magnesium citrate (300 mg/day) was given to the first group (n = 20), amitriptyline (10 mg/day) was given to the second group (n = 20), and magnesium citrate (300 mg/day) with amitriptyline (10 mg/day) treatment was given to the third group (n = 20). Pain intensity, pain threshold, the number of tender points, the Tender Point Index, the Fibromyalgia Impact Questionnaire, the Beck depression and Beck anxiety scores, and the patient symptoms were evaluated in all the women. All parameters were reevaluated after the 8 weeks of treatment. The number of tender points, Tender Point Index, the Fibromyalgia Impact Questionnaire, and beck depression scores decreased significantly with the magnesium citrate treatment. The combined amitriptyline with magnesium citrate treatment proved effective on all parameters except numbness, more effective in all measured outcomes than amitriptyline alone (Table 2). The authors suggested that magnesium might have a beneficial effect in patients with fibromyalgia.

Engen et al³⁵ performed a pilot study to collect preliminary data concerning the effect of transdermal magnesium on fibromyalgia patients through a patient questionnaires and survey in a fibromyalgia clinic at a tertiary medical center. The study enrolled 40 female patients with the diagnosis of fibromyalgia; 24 patients completed the study (mean [SD] age, 57.2 [7.6] years; white, 95%; mean body mass index, 31.3 kg/m²). Each participant was provided a spray bottle containing a transdermal magnesium chloride solution and asked to apply 4 sprays per limb twice daily for 4 weeks. At baseline, week 2, and week 4, participants were asked to complete the Revised Fibromyalgia Impact Questionnaire, 36-Item Short Form Version 2 Health Survey, and a quality-of-life analog scale. The Revised Fibromyalgia Impact Questionnaire subscale and total scores were significantly improved at week 2 and week 4. The authors suggested that transdermal magnesium chloride may be of beneficial use in fibromyalgia.

Martínez-Rodríguez et al³⁶ conducted a randomized, controlled trial, to determine the effects of tryptophan and a magnesium-enriched Mediterranean diet on psychological variables and sleep in women with fibromyalgia. The study included 22 women diagnosed with fibromyalgia. Participants were randomly allocated into experimental (EG) and control (CG) groups (EG: Age = 48 ± 4 years old and body mass index [BMI] = 28.2 ± 3.7 kg/m²) (CG: Age = 50 ± 5 years old and BMI = 28.6 ± 5.1 kg/m²). The experimental group received a Mediterranean diet enriched with high doses of tryptophan and magnesium (60 mg of tryptophan and 60 mg of magnesium). The control group received the standard Mediterranean diet. Before and 16 weeks after the intervention, participants completed Pittsburgh Sleep Quality Questionnaire, Body Shape Questionnaire, State–Trait Anxiety Inventory, Profile of Mood States Questionnaire, Eating Attitudes Test-26, and Trait Anxiety Inventory. Significant differences were found between groups after the intervention for the mean scores of trait anxiety, self-image perception, mood disturbance, and eating disorders. The authors concluded that tryptophan and magnesium-enriched Mediterranean diet improve body image satisfaction, mood state, anxiety symptoms, and eating disorders but do not modify sleep quality in women with fibromyalgia.

In a review, Gaby³⁷ describes his clinical experience with the therapeutic use of intravenous nutrients in fibromyalgia. He gave the modified Myers’ cocktail to about 30 patients with fibromyalgia. The modified Myers’ cocktail consists of magnesium, calcium, B vitamins, and vitamin C. Half of the patients have experienced a significant improvement mostly after 3 or 4 treatments. In his review, Gaby refers to a study that was published only as an abstract in which 86 patients with chronic muscular complaints received intramuscular or intravenous injections of magnesium, either alone or in combination with calcium, B vitamins, and vitamin C, with 74% of the patients demonstrating improvement in their symptoms.³⁸

Ali et al³⁹ devised a randomized, double-blind, placebo-controlled pilot study to assess the feasibility, safety, and provided insights into the efficacy of Myers’ Cocktail. The study included 34 adult fibromyalgia patients. Subjects were randomly assigned either to treatment (weekly infusions of Myers’ Cocktail) or to placebo (weekly infusions of lactated Ringer’s solution) for 8 weeks. Primary outcome was the change in the Tender Point Index, assessed 8 and 12 weeks after initiation. Secondary measures included a visual analog scale to assess global pain, and validated measures of physical function (Fibromyalgia Impact Questionnaire), mood (Beck Depression Index), and quality of life (Health Status Questionnaire 2.0). No statistically significant differences were seen between the treatment and placebo groups, in any outcome measure, at 8 and 16 weeks. The authors concluded that the efficacy of Myers’ Cocktail for fibromyalgia, relative to placebo, remains uncertain.

Abraham and Flechas¹⁴ treated 15 fibromyalgia patients for an 8-week period with a combination of magnesium (300-600 mg) and malate (1200-2400 mg) in a randomized, placebo-controlled, open-label, crossover trial. The treatment group demonstrated improvement in the Tender Point Index scores as well as the myalgia symptoms.

Russell et al⁴⁰ assessed the efficacy of Super Malic (contains 200 mg of malic acid and 50 mg of magnesium/tablet, given as 3 tablets twice a day) in treatment of primary fibromyalgia syndrome. The study included 24 participants with primary fibromyalgia. The participants were randomized to compare the combination of malic acid and magnesium to placebo in a 2-period (4 weeks per period), double blinded, cross-over design trial. The 20 participants who completed the study were analyzed for efficacy through 3 primary and 3 secondary outcome measures. The 3 primary outcome measures assessed pain and tenderness. Measurements included were a patient self-assessment of pain on a 10 cm visual analog scale, the Tender Point Index, and the tender point average. The 3 variables of secondary importance were functional and psychological measures. Variables included the Health Assessment Questionnaire score, the Center for Epidemiologic Studies-Depression Scale score, and the Hassle Scale score. In the blinded trial, there was no significant improvement during the Super Malic treatment period compared to the placebo treatment period.