ALA Supplementation Improves Inflammation, Mood Status in Women With Episodic Migraine

woman with a headache
Researchers investigated the effect of alpha-lipoic acid (ALA) on oxidative, inflammatory, and mood conditions in women with episodic migraine.

Supplementation with alpha-lipoic acid (ALA) for 3 months has beneficial effects in women with episodic migraine, according to study results published in International Journal of Clinical Practice.

In the current single-center, double-blind, randomized parallel-group clinical trial, researchers enrolled women with neurologist-diagnosed episodic migraine. Inclusion criteria were episodic migraine without aura with 2 or more attacks per month, lasting between 4 and 72 hours each, in nonmenopausal, nonpregnant, nonlactating, nonsmoking, and nonalcoholic women aged between 20 and 50 years..

Primary study outcomes were indicators of oxidative stress using C-reactive protein (CRP), reactive oxygen species (ROS), nitric oxide, malondialdehyde (MDA), thiobarbituric acid reactive substances, thiol, catalase, superoxide dismutase, glutathione (GSH), total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) as inflammatory markers. A 10 mL venous blood sample after a 10- to 12-hour fasting period was taken at baseline and after 3 months.

Secondary outcome measures included the mood status using a depression, anxiety, and stress scale (DASS-21 items) questionnaire at baseline and at the end of the intervention.

Participants were randomly assigned to 2 parallel groups: the intervention group (n=47) receiving 300 mg/day ALA supplement capsules twice per day for 3 months; the control group (n=45) receiving the placebo in the same packaging, form, color, and dosage for the same duration.

After dropouts and withdrawal due to the COVID-19 pandemic, 79 of the 92 patients completed the study. After the 3-month intervention with ALA vs placebo, there was a significant reduction in serum MDA (means difference [MD], -0.83; 95% CI, -1.04 to -0.62 nmol/mL vs MD, -0.32; 95% CI, -0.48 to -0.15 nmol/mL; P <.001) and CRP (MD, -0.78; 95% CI, -1.17 to -0.39 mg/L vs MD, -0.63; 95% CI, -1.80 to 0.52 mg/L; P <.001) levels.

Changes in levels of serum markers, including glutathione (GSH; P =.086), total antioxidant capacity (TAC; P =.068), total oxidant status (TOS; P =.225), and oxidative stress index (OSI; P =.404), were not statistically significant.

Depression, anxiety, and stress scores were significantly decreased in the ALA group by the end of study compared with baseline (P <.001 for all); however, no statistically significant changes were detected in the placebo group.

One limitation of the study included the inability to measure ALA serum levels at the beginning and end of the study due to financial constraints. Clinical trials with higher quality and duration of intervention are needed to confirm the efficacy of ALA supplementation in patients with episodic migraine.

“Although the [etiology] of migraine is still unclear, vascular and neurological disorders have been suggested as the contributing factors in migraine pathogenesis,” the researchers concluded. “There is also evidence that impaired mitochondrial metabolism followed by elevated levels of RNS and ROS plays an important role in migraine pain through changes in brain blood flow. The results of our study revealed that ALA reduced levels of oxidative stress and inflammation in patients with migraine due to its antioxidant, anti-inflammatory effects and by improving mitochondrial metabolism. It also caused favorable effects on mood status in these patients.”


Rezaei Kelishadi M, Alavi Naeini A, Askari G, Khorvash F, Heidari Z. The efficacy of alpha-lipoic acid in improving oxidative, inflammatory, and mood status in women with episodic migraine in a randomised, double-blind, placebo-controlled clinical trial. Int J Clin Pract. 2021;75(9):e14455. doi:10.1111/ijcp.14455