Reduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N‐acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham‐Controlled Pilot Study

Abstract

Objective To investigate the preventive effects of a combined antioxidant drug (N‐acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect. Design Randomized, double‐blind, sham‐controlled pilot study. Setting Australian community. Subjects Adults reporting 2 to 8 migraines per month for at least a year. Methods After a 1‐month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below. Results For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (−3.1), moderate/severe headache days (−3.2), migraine duration, headache pain scores, and acute headache medication use. Conclusions This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine.

Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period

“…Our results were consistent with those of a study that found that oxidative stress was elevated during migraine attacks, but not interictally ( 35 ). Oxidative stress plays a major role in migraine pathophysiology ( 36 ). It is generally believed that most migraine triggers or aggravating factors have a link to energy metabolism and oxidative stress ( 6 , 37 ).…”

“…Reasonable research has shown increased oxidative stress parameters and decreased anti-oxidative parameters in migraine patients ( 38 – 40 ). In addition, the prophylactic use of antioxidants can significantly reduce migraine frequency and pain intensity ( 36 ). Our study provides 1 H-MRS-based evidence of oxidative stress playing a role in the pathophysiology of migraine during attack.…”

Migraine patients in Germany - need for medical recognition and new preventive treatments: results from the PANORAMA survey

“…This and the probably increasing frustration of patients mirror the claim for novel migraine therapies, made by the physicians. The development and approval of a new therapeutic approach targeting the CGRP pathway by monoclonal antibodies, as well as the development of novel biological prophylactic migraine treatments [11][12][13][14][15][16][17] with increased efficacy, tolerability and safety hold the promise of overcoming former therapy drawbacks. In this context, a large controlled clinical trial investigating erenumab in patients with episodic migraine showed its efficacy in reducing the number of monthly migraine days and use of acute medication, as well as an improvement in Physical-Impairmentand Everyday-Activities Scores [18].…”

Antioxidant and cytokine levels in plasma of patients with attack and non-attack periods

“…Abnormality in the mitochondria membranes induces excessive generation of ROS in migraine (Li et al 2016;Dong et al 2017). The ROS are scavenged by antioxidants such as GSH and GSHPx (Tripathi et al 2018;Visser et al 2020). Previous data have displayed that migraine attacks decreased antioxidant mechanisms followed an apparent reduction in the levels of GSH and GSHPx, and elevation in the MDA content in the plasma and brain of experimental animals (Nazıroğlu et al 2015;Bütün et al 2015;Oliveira et al 2017a).…”