Table 1.

Studies investigating the relationship between magnesium (Mg) levels and migraine.

Reference	Method of Study	Patients No.	Diagnosis	Outcome	Conclusions
Thomas et al., 2000 [53]	case control	29 + 18	migraine + control	significantly lower concentrations of total Mg in erythrocytes and lymphocytes in migraine	Mg in lymphocytes appears to be the most sensitive index of Mg deficiency
Trauninger et.al. 2002 [54]	case control	20 + 20	migraine + healthy	no significant difference between the groups in the baseline serum and urine Mg concentrations, although the latter tended to be lower in the migraine	Mg retention occurs in patients with migraine after oral loading, suggesting a systemic Mg deficiency
Talebi et al., 2011 [55]	case control	140 + 140	migraine + healthy	the average serum Mg level in migraine was significantly lower, no significant difference between the mean level of serum Mg in migraine with aura and without aura	serum Mg in migraine patients was related to the frequency of migraine attacks, supporting the use of Mg in prevention and treatment of migraine
Samaie et al., 2012 [56]	case control	50 + 50	migraine + healthy	no significant differences, but serum total Mg level was notably lower in the migraine	assessing serum Mg level might predict migraine attacks and help to determine optimal dose of administered Mg for achieving appropriate therapeutic outcome
Assarzadegan et al., 2016 [57]	case control	40 + 40	migraine + healthy	significant lower Mg serum levels during the migraine attacks and between the attacks compared with healthy individuals	the serum level of Mg is an independent factor for migraine
Karim et al., 2021 [58]	cross-sectional analytical	70	migraine	serum Mg level lower in severe migraine in comparison to mild to moderate headache	in all migraine groups Mg within normal range
Pfaffenrath et al., 1996 [61]	double-blind placebo-controlled study	150	migraine	with regard to the number of migraine days or migraine attacks there was no benefit with Mg compared to placebo	there were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal
Walker et al., 2003 [62]	randomised double-blind placebo-controlled parallel	46	healthy	supplementation of the organic forms of Mg citrate and amino-acid chelate showed greater absorption than Mg oxide	supplementation with Mg citrate shows superior bioavailability
Karimi et al., 2021 [63]	single-center, randomized, controlled, double-blind, crossover	31 + 32	migraine + control	Mg oxide vs valproate sodium did not show statistically significant difference in the efficacy of both drugs in migraine preventive	Mg oxide can be equally effective in the prevention of migraine attacks as valproate sodium, additionally without significant side effects
Wang et al., 2003 [65]	randomized, double-blind, placebo-controlled, parallel-group	58 + 60 children of ages 3 to 17 years	migraine + control	a statistically significant downward trend in the frequency and severity of migraine pain was found in the group treated with Mg oxide but not in the placebo group	the study is inconclusive
Morel et al., 2021 [66]	systematic review of RCT	81 RCTs on Mg treatment in pain (18 RCTs in migraine)	different types of pain, including migraine	the greatest number of RCTs covering this issue was found in post-operative pain and migraine treated Mg	additional, programmed clinical trials are needed to achieve a sufficient level of scientific evidence to recommend and optimize the use of magnesium in the treatment of pain, mainly chronic pain
Lindberg et al., 1990 [67]	observational	17	healthy	the level of Mg in urine after an oral loading with two Mg salts - higher after Mg citrate than Mg oxide	Mg citrate is more soluble and bioavailable than Mg oxide
Muehlbauer et al., 1991 [68]	observational	24	healthy	Mg-oxide showed significantly lower absorption than Mg-l-aspartate-HCI (granules/tablets)	Mg-l-aspartate-HCI appear to be the first choice for Mg substitution
Khani et al., 2021 [69]	randomized single-center double-blind parallel-group controlled	82 + 70 + 70 (sodium valproate + magnesium with sodium valproate + magnesium)	migraine	significant reduction of migraine in valproate with Mg group	Mg enhance the antimigraine properties of sodium valproate in combination therapy and reduce the required valproate dose for migraine prophylaxis
Gallelli et al., 2014 [71]	single-blinded, balanced-recruitment, parallel-group, single-center	116 children of ages 5–16	migraine	Mg, acetaminophen, ibuprofen decreased pain intensity, but did not modify its frequency; in both acetaminophen and ibuprofen groups, magnesium significantly reduced the pain frequency	Mg increased the efficacy of ibuprofen and acetaminophen with not age-related effects
Slavin et al., 2021 [72]	cross-sectional	3626	migraine or sever headache	Mg consumption associated with lower odds of migraine	evaluate the role of dietary Mg intake on migraine