Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.

Nutrition journal. 2020;19(1):101
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Plain language summary

Migraine is a chronic neurovascular disorder. Patients with this disorder suffer from severe headaches and also nausea, vomiting, photophobia, and phonophobia during a migraine attack. Several supplementary treatments have been suggested for the management of migraine symptoms. Among these methods, there is the supplementation with micronutrients. The aim of this study was to examine the effect of zinc supplementation on characteristics of migraine attacks in migraine patients. This study is a double-blind randomized clinical trial which included migraine patients, with an age range between 20 and 60 years. Patients were stratified based on age (20–40 and 40–60 years), gender (male and female), and body mass index (18.5–24.9 and 25–30) into different blocks. Then, they were randomly allocated to the intervention or control groups. Results show that when compared to the placebo group, zinc supplementation resulted in a significant reduction in headache severity and migraine attacks frequency. However, the effect on headache severity became statistically non-significant when baseline values of headache severity and potential confounders were taken into account. Authors conclude that zinc supplementation was beneficial for migraine attack frequency but not for migraine attack duration and headache daily results.

Expert Review


Conflicts of interest: None

Take Home Message:
  • Inadequate zinc intake may drive migraine frequency.
  • Zinc supplementation may enhance the effectiveness of routine migraine treatment in reducing migraine frequency.

Evidence Category:
  • X A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
  • B: Systematic reviews including RCTs of limited number
  • C: Non-randomized trials, observational studies, narrative reviews
  • D: Case-reports, evidence-based clinical findings
  • E: Opinion piece, other

Summary Review:
Migraines, characterised by severe headaches, nausea, vomiting, photophobia, and phonophobia affect approximately 10-20% of the global population. The authors refer to observational studies that have identified a moderate rate of zinc deficiency amongst migraine sufferers.

Zinc, an essential trace mineral, may prove beneficial as a supplement to reduce migraine symptoms and frequency possibly due to its effects on the nervous system and its antioxidant and anti-inflammatory capacity..

This double blind randomised clinical trial analysed the effects of 220mg of zinc sulphate (50mg of elemental zinc) combined with a routine migraine treatment versus a control group receiving a placebo and the routine treatment on symptoms of migraine attacks. The study duration was 8 weeks occurring from January 2016 to April 2016. Each group consisted of 40 participants between the ages of 20 and 60 with >5 years of migraines or migraine symptoms.

When compared to the placebo group, zinc supplementation demonstrated:

  • A reduction in headache severity (− 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01). This result became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity.
  • A reduction in migraine attacks frequency (− 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02).

Clinical practice applications:
This randomised controlled trial highlights that zinc supplementation combined with routine migraine treatment (200/500 mg sodium valproate (such as Depakin), 50/100 mg sumatriptan, or 1 mg ergotamine) may assist in the reduction of migraine attack frequency amongst migraine sufferers within 8 weeks.

Compliance rate for this study was very high at 100% and there were no adverse effects reported suggesting a potentially safe and convenient treatment for migraine sufferers.

Considerations for future research:
  • Further trials with better dietary controls would be useful to eliminate potential confounders.
  • Use of CONSORT guidelines for reporting randomised trials would strengthen research reporting.
  • Analysis of biomarkers may assist in identifying the mechanisms in which zinc may relieve migraine symptoms..
  • Larger randomised controlled trials with increased sample sizes and longer durations are needed in order to definitively determine the effect of zinc supplementation on migraine attacks and any differences between genders.
  • Additional studies trialling various zinc dosages and forms may provide insight into an optimal zinc dose and form for migraine attacks.

Abstract

BACKGROUND Observational studies have shown a link between zinc deficiency and migraine headaches. We aimed to examine the effect of zinc supplementation on the characteristics of migraine attacks in patients with migraine. METHODS This randomized clinical trial was conducted on 80 patients with migraine. Patients were randomly assigned to receive either zinc sulfate (220 mg/d zinc sulfate) or placebo (lactose) for 8 weeks. Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache severity, frequency and duration of migraine attacks, and headache daily results) were assessed at baseline and end of the trial. RESULTS Compared with the placebo, zinc supplementation resulted in a significant reduction in headache severity (- 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01) and migraine attacks frequency (- 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02) in migraine patients. However, the observed reduction for headache severity became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity. Other characteristics of migraine attacks including the duration of attacks and headache daily results were not altered following zinc supplementation either before or after controlling for covariates. CONCLUSION Zinc supplementation had a beneficial effect on the frequency of migraine attacks in migraine patients. Additional well-designed clinical trials with a long period of intervention and different dosages of zinc are required. TRIAL REGISTRATION CODE IRCT20121216011763N23 at www.irct.ir .

Lifestyle medicine

Fundamental Clinical Imbalances : Neurological
Patient Centred Factors : Mediators/Migraine
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Blood

Methodological quality

Jadad score : 5
Allocation concealment : Yes

Metadata