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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.
Rezaei Kelishadi, M, Alavi Naeini, A, Askari, G, Khorvash, F, Heidari, Z
International journal of clinical practice. 2021;75(9):e14455
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Expert Review
Conflicts of interest:
None
Take Home Message:
- 300mg of ALA twice a day has demonstrated efficacy as an anti-inflammatory and antioxidant agent when used continuously over 3 months in migraine patients.
- ALA can improve mood and reduce stress, depression and anxiety scores in patients treated for 3 months.
- ALA can improve mitochondrial metabolism.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Migraines are common neurovascular conditions that may be linked to oxidative stress and inflammation. ALA possesses antioxidant, anti-inflammatory properties.
This study is a double-blind placebo controlled clinical trial conducted with a total of 92 women experiencing episodic migraines. The study aim was to assess the efficacy of Alpha Lipoic acid on oxidative, inflammatory and mood disorders in women with episodic migraines.
The participants were 92 non-menopausal women with episodic migraines between the ages of 20 and 50. They were randomized and split into two groups, the intervention group receiving 300mg of ALA supplements twice a day for 3 months and the control group receiving Placebo cellulose capsules.
The particiants oxidative and inflammatory status was assessed at the start of the study and after 3 months, by measuring Total Antioxidant Capacity (TAC), total oxidant status (TOS), glutathione (GSH), malondialdehyde (MDA), oxidative stress index (OSI), and C-reactive protein (CRP). Questionnaires such as DASS-21 were used to assess depression and anxiety scales.
Out of the 92 particiants , 79 completed the study. Results showed a significant reduction in Depression (MD: −6.09, CI: −9.07, −3.11 vs MD: 1.35, CI: −1.28, 3.99), anxiety (MD: −6.52, CI: −9.08, −3.96 vs MD: 0.56, CI: −2.76, 3.90) and stress scores (MD: −7.83, CI: −10.66, −5 vs MD: 2.08, CI: −0.39, 4.55) in the study group compared to the placebo. There was also a significant reduction in serum levels of MDA (end product of lipid peroxidation) (means difference [MD]: − 0.83, 95%, confidence intervals [CI]: −1.04, −0.62 nmol/mL vs MD: −0.32, CI: −0.48, −0.15 nmol/mL; P < .001) and CRP(MD: −0.78, CI: −1.17, −0.39 mg/L vs MD: −0.63, CI: −1.80, 0.52 mg/L; P < .001) for the ALA treated group. The changes in oxidative status markers such as GSH (MD: 32.42, CI: −5.02, 69.87 μmol/L/mL vs MD: 0.47, CI: −46.02, 46.98 μmol/L/mL; P = .086), TAC (MD: 173, CI: 69.67, 276 μmol/L/mL Trolox Equivalent vs MD: 100, CI: −18.03, 218 μmol/L/mL Trolox Equivalent; P = .068), TOS (MD: −5.96, CI: −7.27, −4.66 μmol/L/mL vs MD: −3.48, CI: −4.80, −2.17 μmol/L/ mL; P = .225), and OSI (MD: −0.63, CI: −0.75, −0.50 vs MD: −0.37, CI: −0.52, −0.22; P = .404)were not statistically significant.
To conclude, the results of the study showed that ALA supplementations for 3 months reduced levels of oxidative stress and inflammation in patients suffering from migraine owing to its anti-inflammatory and antioxidant effect by improving metabolic mitochondrial function thus improving mood status in those patients.
Clinical practice applications:
- This paper highlights the useful role of 300mg of ALA supplements twice a day in helping patients with recurrent migraines
- ALA has shown useful anti-inflammatory effects by reducing CRP and MDA significantly in this three month study.
- ALA can reduce depression, anxiety and stress scores significantly when taken for 3+ months.
- ALA should be considered in patients with migraines due to its demonstrated anti-oxidant effect, anti-inflammatory effect.
Considerations for future research:
- More double-blind controlled placebo studies on effects of ALA on mood and psychiatric disorders would be valuable.
- There should also be more studies exploring changes in levels of ALA in serum over time as well as changes in levels of other antioxidants such as GSH over a longer duration e.g. 6-12 months.
- Further studies are required to analyse changes in migraines e.g. frequency, intensity, aura, following supplementations with ALA and GSH.
Abstract
AIM: Migraine is a common neurovascular disorder, which is associated with severe to moderate disabling headaches. Oxidative stress and inflammation might play a role in migraine pathogenesis and the mood disorders. Considering the antioxidant and anti-inflammatory properties of alpha-lipoic acid (ALA), this study was designed to investigate its effect on oxidative, inflammatory, and mood conditions in women with episodic migraine. METHODS In total, 92 women with episodic migraine participated in the study. The patients were randomly divided into two groups, receiving a 300-mg capsule of ALA or placebo twice daily for 3 months. To assess the oxidative and inflammatory status, the serum levels of total antioxidant capacity (TAC), total oxidant status (TOS), glutathione (GSH), malondialdehyde (MDA), oxidative stress index (OSI), and C-reactive protein (CRP) were determined at the beginning and at the end of the intervention. A depression, anxiety, stress scale (DASS-21-items) questionnaire was used to evaluate mood status. RESULTS Finally, 79 patients reached the final analysis stage. At the end of the intervention, a significant decrease in the serum levels of MDA (means difference [MD]: -0.83, 95% confidence intervals (CI): -1.04, -0.62 nmol/mL vs MD: -0.32, CI: -0.48, -0.15 nmol/mL; P < .001) and CRP (MD: -0.78, CI: -1.17, -0.39 mg/L vs MD: -0.63, CI: -1.80, 0.52 mg/L; P < .001) was observed in the ALA as compared with the placebo group, but changes in serum GSH (P = .086), TAC (P = .068), TOS (P = .225), and OSI (P = .404) were not statistically significant. In addition, depression, anxiety, and stress (with P < .001, in all cases) had significantly decreased in the intervention as compared with the control group. CONCLUSION The results of this study suggest that ALA supplementation for 3 months has beneficial effects on improving the oxidative, inflammatory, and mood conditions of patients suffering from episodic migraine.
2.
Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.
Ahmadi, H, Mazloumi-Kiapey, SS, Sadeghi, O, Nasiri, M, Khorvash, F, Mottaghi, T, Askari, G
Nutrition journal. 2020;19(1):101
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Free full text
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:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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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 .