Serum Levels of GDF-15 and FGF-21 May be Markers for Migraine Severity

Migraine and severity of migraine may be related to serum levels of growth-differentiation-factor 15 (GDF-15) and fibroblast-growth-factor 21 (FGF-21), according to study findings published in The Journal of Headache and Pain.

Researchers conducted the study at the Second Affiliated Hospital of Zhejiang University in China between 2019 and 2023. Patients (n=221) with migraine and healthy control individuals (n=124) provided blood samples; the levels of GDF-15 and FGF-21 were compared.

The patients and control individuals were mean age, 40.50±0.88 and 38.98±1.00 years; 22.17% and 19.35% were men; and they had a body mass index (BMI) of 22.11±0.24 and 21.92±0.29 kg/m², respectively. Among the patients, 153 had episodic migraine and 68 had chronic migraine. The patients with episodic migraine were younger (mean, 38.33 vs 45.38 years; P <.001), they had fewer monthly migraine days (mean, 3.73 vs 23.12 days; P <.001), fewer had medication overuse headache (0% vs 48.53%; P <.001), and fewer used analgesics (30.72% vs 76.47%; P <.001), respectively.

Overall, the migraine group had significantly higher levels of FGF-21 (mean, 259.53 vs 103.49 pg/mL; P <.001) and GDF-15 (mean, 944.44 vs 401.63 pg/mL; P <.001) compared with control individuals, respectively.

Among the migraine group, those with chronic migraine had significantly higher FGF-21 levels (mean, 313.68 vs 235.30 pg/mL; P =.026) but similar levels of GDF-15 (mean, 1022.45 vs 909.76 pg/mL; P =.290) compared with episodic migraine, respectively. Stratified by the status of medication overuse headache, no trends in FGF-21 or GDF-15 were observed.

Significant correlations were observed between FGF-21 levels and age (r, 0.285; P <.001), family history (r, -0.148; P =.035), 6-item Headache Impact Test (HIT-6) scores (r, 0.266; P <.001), and Migraine Disability Assessment (MIDAS) scores (r, 0.375; P <.001) and between GDF-15 levels and age (r, 0.233; P <.001), HIT-6 scores (r, 0.297; P <.001), and MIDAS scores (r, 0.368; P <.001).

In the receiver operating characteristic curve analyses, GDF-15 was able to differentiate individuals with migraine (area under the curve [AUC], 0.801; P <.001), chronic migraine (AUC, 0.880; P <.001), and episodic migraine (AUC, 0.780; P <.001) from control individuals. FGF-21 was able to differentiate individuals with migraine (AUC, 0.729; P <.001), chronic migraine (AUC, 0.755; P <.001), and episodic migraine (AUC, 0.699; P <.001) from control individuals.

The major limitation of this study was that blood samples were only collected at one time point. It remains unclear whether fluctuations in GDF-15 or FGF-21 over time affect migraine symptoms.

This study found a relationship between serum GDF-15 and FGF-21 levels with migraine symptoms, leading the researchers to conclude, “The heightened concentrations of GDF-15 and FGF-21 are linked to greater disease burden, indicating their potential as peripheral blood markers for evaluating the severity of migraine-related disability.”