Serum magnesium levels and their association with sleep quality and disease severity in fibromyalgia syndrome: An observational cross-sectional study

Abstract

Fibromyalgia syndrome (FMS) is a multifactorial condition characterized by chronic widespread pain, fatigue, and sleep disturbances, often accompanied by biochemical and psychosocial alterations. Sleep quality plays a critical role in disease severity and patient functionality. Recent evidence suggests that magnesium may influence both pain and sleep regulation. This observational cross-sectional study aimed to investigate the relationship between sleep quality and serum magnesium levels in patients with FMS and to explore their associations with clinical characteristics such as pain severity and functional status. Eighty-two patients diagnosed with FMS were grouped based on their Pittsburgh Sleep Quality Index (PSQI) scores: PSQI ≤ 5 (n = 27) and PSQI > 5 (n = 55). Demographic and clinical parameters, including age, body mass index, tender points, Fibromyalgia Impact Questionnaire (FIQ), and serum magnesium levels, were compared between the groups. Correlation analyses were performed to assess associations between magnesium levels and clinical variables. No significant differences were found between the groups in terms of age and body mass index (P > .05 for all). The PSQI > 5 group demonstrated significantly higher tender points (P = .035), visual analog scale scores (P = .002), FIQ scores (P < .001), and lower serum magnesium levels (P = .038) compared to the PSQI ≤ 5 group. Significant negative correlations were observed between magnesium levels and tender points (ρ = −0.293, P = .008), visual analog scale score (ρ = −0.252, P = .023), FIQ scores (ρ = −0.242, P = .028), PSQI scores (ρ = −0.324, P = .003). The findings indicate that lower serum magnesium levels are associated with poorer sleep quality, higher pain severity, and greater functional impairment in patients with FMS. These findings suggest a potential link between magnesium levels and the pathophysiology of sleep disturbances in FMS. However, due to the cross-sectional nature of the study and possible confounding influences, further longitudinal and interventional research is required to determine whether magnesium supplementation could offer clinical benefits in this population.

1. Introduction

Fibromyalgia syndrome (FMS) is a complex and multifaceted disorder characterized by chronic widespread pain, fatigue, sleep disturbances, and various psychosocial factors. The diagnosis of FMS is made by excluding other conditions that may cause similar symptoms, as its exact etiology and pathophysiology remain unclear.^[1,2] With a global prevalence of approximately 2% to 3%, FMS is frequently associated with sleep disorders, cognitive dysfunction, anxiety, and depression, significantly reducing individuals’ quality of life.^[3,4]

Studies have shown that poor sleep quality exacerbates pain and fatigue, making the management of fibromyalgia more challenging.^[5,6] Sleep quality has been identified as a critical determinant of functionality in patients with FMS. Additionally, severe pain has also been reported to contribute to sleep disturbances.^[7] Increased rapid eye movement (REM) sleep is associated with good health, and in healthy individuals, REM sleep accounts for 25% of total sleep duration.^[8,9] Electroencephalographic findings have been observed in patients with FMS, revealing abnormalities in both REM and non-REM sleep stages.^[10] Therefore, sleep quality is a crucial therapeutic target that must be improved in patients with FMS. The Pittsburgh Sleep Quality Index (PSQI) is frequently used to assess sleep quality, providing valuable insights into the relationship between sleep and other clinical parameters.^[11]

Nutritional supplements used in the management of FMS have been shown to be effective in reducing symptoms. In a study evaluating magnesium levels in patients with FMS, those with lower magnesium levels were found to have higher pain and tenderness severity.^[12] Additionally, studies assessing the relationship between magnesium and sleep quality have linked low magnesium levels to poor sleep quality and higher pain scores.^[13,14] This underscores the importance of considering biochemical factors alongside psychological and physical symptoms in the treatment of FMS.

Given the interplay between sleep disturbances, pain, and biochemical factors such as magnesium in the pathophysiology of FMS, understanding these relationships is essential for effective management. This study aimed to investigate the relationship between sleep quality and serum magnesium levels in patients with FMS, and to explore their associations with clinical characteristics such as pain severity and functional status.

2. Materials and methods

This observational cross-sectional study was conducted at a tertiary care outpatient clinic of Bolu İzzet Baysal Physical Therapy and Rehabilitation Education and Research Hospital. A total of 98 female patients aged between 18 and 65 years who fulfilled the 2016 revised criteria of the American College of Rheumatology^[15] for the diagnosis of FMS were consecutively recruited. Exclusion criteria included the presence of inflammatory rheumatic diseases, major psychiatric disorders, chronic renal or hepatic disease, use of magnesium supplementation in the last 3 months, or any condition known to affect absorption of magnesium or serum magnesium levels (such as using proton pump inhibitors, diuretics). Based on these criteria, 16 patients were excluded from the study: 11 due to magnesium supplementation or using PPI or using diuretics, 2 due to a diagnosis of rheumatoid arthritis, and 3 due to major psychiatric illness. As a result, 82 patients were included in the final analysis. The study protocol was approved by the Non-Interventional Clinical Research Ethics Committee of Bolu Abant İzzet Baysal University (approval number: 2025/06, date: 21.01.2025). Written informed consent was obtained from all participants prior to enrollment. The study was conducted in accordance with the principle of the Declaration of Helsinki.

Demographic data including age, marital status, and body mass index were recorded. Clinical data included disease duration (in months), the number of tender points (assessed by manual palpation), current pharmacological treatments, pain intensity levels were assessed using the 100 cm visual analog scale (VAS), and functional impact assessed using the Fibromyalgia Impact Questionnaire (FIQ).

The FIQ is a validated self-reported instrument used to assess physical functioning, overall impact of the disease, and symptom severity in patients with fibromyalgia. Originally developed by Burckhardt et al, the FIQ has been adapted into Turkish and its validity and reliability have been confirmed.^[16,17] Total scores range from 0 to 100, with higher scores indicating greater disease impact and worse functional status.

The PSQI is a self-reported questionnaire developed by Buysse et al to assess subjective sleep quality and disturbances over a 1-month period. The scale comprises 24 items and evaluates 7 components of sleep, generating a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality.^[18] The Turkish version of the PSQI has undergone validity and reliability testing.^[19] Patients were stratified into 2 groups based on PSQI scores: good sleepers (PSQI ≤ 5) and poor sleepers (PSQI > 5).

Venous blood samples were collected from all participants following an overnight fasting period. Serum magnesium concentrations were measured using a colorimetric spectrophotometric method with the Abbott Architect c4000 clinical chemistry analyzer (Abbott, Abbott Park). All analyses were performed in the same institutional biochemistry laboratory under standardized protocols.

2.1. Statistical analysis

All statistical analyses were performed using JMP Pro 18 (Student Edition; SAS Institute Inc., Cary). The distribution of continuous variables was assessed using the Shapiro–Wilk test. Descriptive statistics were presented as mean ± standard deviation or median (interquartile range [1st to 3rd quartile values]) depending on data distribution. Between-group comparisons (PSQI ≤ 5 vs PSQI > 5) were performed using the Student t test for normally distributed continuous variables and the Mann–Whitney U test for non-normally distributed variables. Categorical variables were presented as number (percent value). Correlations between serum magnesium levels and clinical parameters (tender points, FIQ, PSQI) were assessed using Spearman’s rank correlation coefficient. A P value of <.05 was considered statistically significant.

3. Results

A total of 82 female patients diagnosed with FMS were included in the study. The mean age of the participants was 44.2 ± 10.0 years. The majority of the patients (n = 73.89%) were married. Among the participants, 62 (75.6%) were newly diagnosed, while 19 (23.2%) were using duloxetine and 1 (1.2%) was on pregabalin treatment.

When the participants were divided into 2 groups based on their PSQI scores into good (PSQI ≤ 5, n = 27) and poor sleepers (PSQI > 5, n = 55), significant differences were observed in clinical parameters (Table 1). While age and body mass index did not differ significantly between the groups (P = .316 and P = .626, respectively), patients with poorer sleep quality had significantly higher tender point counts (median: 12 [8–16] vs 10 [6–12]; P = .035), higher VAS scores (median: 80 [70–90] vs 60 [40–80]; P = .002), and FIQ scores (59.0 ± 10.1 vs 44.9 ± 16.9, P < .001). Moreover, serum magnesium levels were significantly lower in patients with poor sleep quality (2.0 ± 0.41 mg/dL vs 2.2 ± 0.4 mg/dL, P = .038).

Table 1.

Comparison of clinical and demographic characteristics between FMS patients with PSQI ≤ 5 and PSQI > 5.

	PSQI ≤ 5 (N = 27)	PSQI > 5 (N = 55)	P value
Age, yr	45.8 ± 10.9	43.4 ± 9.5	.316*
BMI, kg/m2	28.0 ± 4.2	28.6 ± 5.7	.626*
Tender points, N	10 (6–12)	12 (8–16)	.035**
Disease duration, mo	36 (12–66)	36 (12–60)	.763**
FIQ	44.9 ± 16.9	59.0 ± 10.1	<.001*
VAS	60 (40–80)	80 (70–90)	.002**
Mg, mg/dL	2.2 ± 0.4	2.0 ± 0.41	.038*

Descriptives are shown as Median (1st to 3rd quartile) values or mean ± standard deviation.

BMI = body mass index, FIQ = Fibromyalgia Impact Questionnaire, Mg = magnesium, PSQI = Pittsburgh Sleep Quality Index, VAS = visual analog scale.

^*Student t test.

^**Mann–Whitney U test.

Correlation analyses further revealed that serum magnesium levels were negatively correlated with the number of tender points (ρ = –0.293, P = .008), FIQ scores (ρ = –0.242, P = .028), VAS score (ρ = −0.252, P = .023) and PSQI scores (ρ = –0.324, P = .003; Fig. 1). Additionally, the number of tender points showed positive correlations with both FIQ (ρ = 0.370, P = .001) and VAS scores (ρ = 0.320, P = .003). Significant positive correlations were observed between PSQI scores and VAS (ρ = 0.458, P < .001), tender point count (ρ = 0.307, P = .005), and FIQ scores (ρ = 0.562, P < .001).

Figure 1.

Correlation matrix depicting relationships between serum magnesium levels, sleep quality (PSQI), disease impact (FIQ), number of tender points, and pain intensity (VAS) in patients with fibromyalgia syndrome. Spearman’s correlation coefficients (ρ) and corresponding P values are presented in the upper triangle. Circle size and color intensity indicate the strength and direction of the correlations, with blue representing negative and red representing positive correlations. Scatter plots with fitted regression lines and 95% confidence intervals are shown in the lower triangle. FIQ = Fibromyalgia Impact Questionnaire, PSQI = Pittsburgh Sleep Quality Index, VAS = visual analog scale.

4. Discussion

In the present study, we investigated the relationship between sleep quality and various clinical parameters in patients with FMS. Our findings revealed that poorer sleep quality, as measured by the PSQI, was significantly associated with higher pain intensity (assessed by the VAS), greater tenderness (tender point count), higher functional impairment (measured by the FIQ), and lower serum magnesium levels.

In a study, it was shown that non-restorative sleep the previous night was associated with higher morning pain in FMS patients, more than 90% of whom were known to have sleep problems.^[20,21] The lack of restorative sleep may result in deficiencies of neurotransmitters involved in pain modulation, such as serotonin and growth hormone, and reduced activity in descending inhibitory pain pathways.^[22] On the other hand, the interruption of delta activity and slow-wave sleep by alpha activity reduces the pain-relieving effects of synaptic downscaling, thereby lowering the musculoskeletal pain threshold and contributing to fatigue and low energy levels.^[23] Poor sleep not only leads to a decreased pain threshold but also impairs cognitive abilities and increases the likelihood of depression, anxiety, and stress in affected individuals.^[24] Studies have shown that sleep disorders, along with chronic pain and depression, further worsen somatic and psychological symptoms, negatively impacting the quality of life of individuals.^[25] Similarly in our study, patients with a PSQI score > 5 (indicating poor sleep quality) were found to have significantly higher tender point counts, FIQ scores, and VAS scores. These results highlight a strong association between sleep quality and disease severity in FMS, though the direction of this relationship remains to be fully elucidated.

In our study, significant negative correlations were identified between low magnesium levels and higher tender point counts, as well as higher FIQ, VAS and PSQI scores. This suggests that magnesium deficiency may worsen the clinical manifestations of FMS. The role of magnesium in regulating muscle function is related to its function as a cofactor in adenosine triphosphate production. Low adenosine triphosphate levels are common in FMS patients and play a critical role in the development of many symptoms.^[26] Additionally, low magnesium levels can lead to increased substance P, thereby enhancing pain and stress-related hormones.^[27] Magnesium also regulates the synthesis of various nerve receptors, such as N-methyl-d-aspartate receptors, which are involved in the development of neuropathic pain. Its ability to block these receptors suggests that magnesium may help alleviate pain-related symptoms.^[28,29]

Recent studies have reported that 36% of FM patients use magnesium supplements.^[30] However, detecting magnesium deficiency in practice is challenging because serum levels are often compensated by magnesium release from bone reservoirs.^[31] Therefore, individuals may have a chronic negative magnesium balance without overt hypomagnesemia and could potentially benefit from magnesium supplementation.^[32] Studies in the literature, consistent with our findings, indicate that higher magnesium levels may reduce pain experiences in fibromyalgia patients.^[13]

The negative correlation between sleep disorders and magnesium levels is also a noteworthy finding in our study. Low magnesium levels may lead to decreased melatonin levels, resulting in sleep disturbances.^[26] However, the lack of randomized controlled studies on this topic is striking.^[33] A recent review has shown that randomized controlled studies demonstrate an unclear relationship between magnesium supplementation and sleep disorders.^[34] Additionally, another study evaluating the impact of a magnesium-enriched Mediterranean diet on sleep quality in female FMS patients concluded that higher magnesium levels did not improve sleep quality.^[14] The conflicting results from these studies highlight the need for further research on this topic.

While this study provides evidence of significant associations between serum magnesium levels, sleep quality, and disease severity in patients with fibromyalgia, several limitations should be noted. The relatively small sample size and the fact that it was conducted at a single center limit the generalizability of the findings. The cross-sectional design precludes causal inferences; thus, the observed associations do not imply directional or mechanistic relationships. Additionally, although major confounders were excluded by design, other potentially relevant factors such as physical activity, dietary intake, stress levels, and detailed medication history (e.g., duration or dosage of antidepressants, participation in rehabilitation programs) were not systematically controlled. These variables may have influenced both serum magnesium levels and sleep parameters. Therefore, the results should be interpreted with caution, and future longitudinal or interventional studies are warranted to better establish causality and clarify the role of confounding factors.

In conclusion, this study demonstrated that poor sleep quality in patients with FMS is associated with increased disease severity and pain intensity. Moreover, lower serum magnesium levels were found to be associated with poorer sleep quality and more severe clinical symptoms. While these associations suggest a possible role of magnesium in the symptomatology of FMS, the cross-sectional design and lack of control for certain confounding variables preclude causal interpretations. Therefore, further longitudinal and interventional studies are needed to clarify the nature of these relationships and evaluate the potential clinical utility of magnesium supplementation in this population.

Author contributions

Conceptualization: Tugba Alisik, Esra Sahingoz Bakirci.

Data curation: Yagmur Cagla Reis Altan, Sevde Gul Olkay.

Formal analysis: Tugba Alisik.

Investigation: Tugba Alisik, Sevde Gul Olkay.

Methodology: Tugba Alisik, Esra Sahingoz Bakirci.

Validation: Tugba Alisik, Yagmur Cagla Reis Altan, Sevde Gul Olkay, Esra Sahingoz Bakirci.

Visualization: Tugba Alisik.

Writing – original draft: Tugba Alisik, Yagmur Cagla Reis Altan.

Writing – review & editing: Tugba Alisik, Yagmur Cagla Reis Altan, Sevde Gul Olkay, Esra Sahingoz Bakirci.