A recent study published in Scandinavian Journal of Pain reports that both resistance exercise and relaxation therapy can significantly increase plasma 25-hydroxyvitamin D3 levels in women with fibromyalgia, while baseline associations between vitamin D and inflammatory cytokines were no longer evident following intervention. The findings provide new insight into the interplay between physical activity, metabolic regulation, and inflammation in fibromyalgia, a condition characterized by central sensitization, chronic widespread pain, and fatigue.
Vitamin D, particularly in its circulating form 25-hydroxyvitamin D3, plays a critical role in immune modulation, calcium homeostasis, and musculoskeletal health. It has also been implicated in the pathophysiology of several autoimmune and inflammatory disorders, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus, and irritable bowel syndrome. Deficiency has been associated with chronic pain syndromes, impaired neuromuscular function, and increased inflammatory activity. In clinical practice, symptoms of vitamin D deficiency such as diffuse musculoskeletal pain and fatigue often overlap with fibromyalgia, complicating diagnosis and management.
Fibromyalgia is increasingly understood as a disorder involving dysregulation of both the central nervous system and peripheral inflammatory pathways. Altered cytokine profiles, neurotransmitter imbalance, and increased pain sensitivity are hallmarks of the disease. Vitamin D deficiency may exacerbate these mechanisms by promoting pro-inflammatory cytokine production and impairing neuromuscular function. In addition, patients with fibromyalgia frequently exhibit reduced outdoor activity and limited sunlight exposure due to pain, fatigue, and associated mood disturbances, further predisposing them to hypovitaminosis D and creating a potential bidirectional relationship.
The study was conducted as a sub-analysis of a larger randomized controlled multicentre trial involving 84 women with fibromyalgia aged 20 to 65 years and 36 age-matched healthy controls. Participants with fibromyalgia were randomized to either resistance exercise or relaxation therapy over a 15-week period. Outcomes included physical capacity, symptom burden, and biochemical markers such as plasma 25-hydroxyvitamin D3 and inflammatory cytokines.
At baseline, patients with fibromyalgia had significantly lower vitamin D levels compared to controls (78.0 vs 90.6 nmol/L; p=0.041). Following intervention, vitamin D levels increased significantly in the fibromyalgia group (p<0.001), irrespective of whether participants underwent resistance training or relaxation therapy, while no significant changes were observed in the control group. This suggests that structured interventions, even those not directly involving physical exertion, may influence metabolic and endocrine pathways linked to vitamin D regulation.
Multivariate analysis demonstrated that while several cytokines were associated with vitamin D levels at baseline, these relationships were no longer present after the intervention. This finding may indicate a normalization or decoupling of inflammatory signaling from vitamin D status following therapeutic intervention, potentially reflecting improved systemic regulation. The absence of persistent cytokine associations also suggests that vitamin D may act as part of a broader network of immunometabolic factors rather than as a single dominant driver of inflammation.
The study also highlighted heterogeneity in treatment response, with distinct patient subgroups demonstrating variable improvements in both clinical symptoms and biochemical markers. Such variability underscores the need for personalized approaches in fibromyalgia management, integrating physical therapy, behavioural interventions, and metabolic optimization. From a clinical perspective, these findings reinforce the importance of monitoring vitamin D status in fibromyalgia patients and suggest that non-pharmacological interventions may have broader biological effects beyond symptom control.
While the results are promising, the authors emphasize that the clinical implications require validation in larger, well-powered studies with longer follow-up. Future research may explore whether optimizing vitamin D levels through targeted interventions can lead to sustained improvements in pain, function, and quality of life, and whether vitamin D modulation can serve as a biomarker for treatment response in fibromyalgia.
References
- Samefors M, Rådholm K, Östgren CJ, Ernberg M, Mannerkorpi K, Kosek E, Ghafouri B. Plasma vitamin D and cytokines in relation to exercise in patients with fibromyalgia- A 15-week strength training intervention trial. Scand J Pain. 2026 Mar 11;26(1).
- Makrani AH, Afshari M, Ghajar M, Forooghi Z, Moosazadeh M. Vitamin D and fibromyalgia: a meta-analysis. Korean J Pain. 2017 Oct;30(4):250-257.
- Ersoy S, Kesiktas FN, Sirin B, Bugdayci D, Paker N. The effect of vitamin D treatment on quality of life in patients with fibromyalgia. Ir J Med Sci. 2024 Apr;193(2):1111-1116.