Unraveling the nutritional challenges in epilepsy: Risks, deficiencies, and management strategies: A systematic review

Table 2 Summary of quality assessment and key findings from studies on minerals and epilepsy¹

Ref.	Mineral studied	Sample size (n)	Risk of bias (Cochrane tool)	Main outcome	Statistical findings (P value, 95%CI, etc.)
Baek et al[122], 2018	Magnesium	274 (133 cases, 141 controls)	Moderate (case-control, potential confounders)	Hypomagnesemia more common in febrile seizure patients	OR = 22.12 (95%CI = 9.23-53.02), P < 0.001
Abdelmalik et al[124], 2012	Magnesium	22	High (retrospective, no control group)	Magnesium supplementation reduced seizure frequency	Seizure days reduced (P = 0.021 at 3-6 months, P = 0.004 at 6-12 months)
Guo et al[125], 2023	Magnesium, calcium	44889 (15212 cases, 29677 controls)	Low (mendelian randomization, large sample)	Higher serum magnesium associated with lower epilepsy risk	OR = 0.28 (95%CI = 0.12-0.62), P = 0.002
Abdullahi et al[126], 2019	Magnesium, calcium	90 (40 idiopathic epilepsy, 20 symptomatic epilepsy, 30 controls)	Moderate (case-control, small sample)	Lower serum magnesium and calcium in epilepsy patients	Mg: P = 0.007 (95%CI = -0.189 to -0.031), Ca: P < 0.01
Saghazadeh et al[131], 2015	Magnesium, zinc, copper, selenium	60 studies (Meta-analysis)	Low (large sample, multiple studies)	Altered trace element levels in epilepsy and febrile seizures	Magnesium significantly lower in epilepsy (P < 0.001)
Kheradmand et al[132], 2014	Zinc, copper	70 (35 intractable epilepsy, 35 controlled epilepsy)	Moderate (case-control, small sample)	Zinc deficiency more common in intractable epilepsy	P < 0.05 (71.45% deficiency in intractable vs 25.72% in controlled epilepsy)
Saad et al[133], 2014	Zinc, selenium	80 (40 epilepsy, 40 controls)	Moderate (case-control, small sample)	Lower Zn, Se in epilepsy patients, higher oxidative stress markers	Zn, Se significantly lower (P < 0.001), Plasma MDA higher (P < 0.001)
Chen et al[134], 2019	Zinc	Animal study (Sprague-Dawley rats)	Moderate (preclinical, no human data)	Zinc deficiency worsened seizure-related brain damage	No direct P value reported, hippocampal ZnT-3 and MBP levels altered
Sharif et al[158], 2015	Iron	200 (100 febrile seizure, 100 controls)	Moderate (case-control, single-center)	Iron deficiency more common in febrile seizure patients	45% iron deficiency in seizure group vs 22% in controls (P < 0.05)
Bidabadi et al[159], 2009	Iron	200 (100 febrile seizure, 100 controls)	Moderate (case-control, single-center)	No protective effect of iron deficiency against febrile seizures	OR = 1.175, temperature peak higher in seizure group (P < 0.0001)
Zimmer et al[160], 2021	Iron	Human and animal study	Low (well-controlled, experimental)	Seizures linked to iron accumulation in temporal lobe epilepsy	P < 0.01, iron metabolism changes observed in TLE
Ashrafi et al[168], 2007	Selenium	160 (80 intractable epilepsy, 80 controls)	Moderate (case-control, no intervention)	Serum selenium lower in intractable epilepsy patients	P < 0.05 (lower selenium in epilepsy group)
Omrani et al[175], 2019	Omega-3 fatty acids	50 (randomized clinical trial)	Low (double-blind, placebo-controlled)	Omega-3 reduced seizure frequency and inflammation	P < 0.001 (seizure reduction), lower TNF-α and IL-6
Liang et al[174], 2023	Omega-3 fatty acids	Mendelian randomization	Low (genetic analysis, large sample)	Higher blood omega-3 levels linked to increased epilepsy risk	OR = 1.16 (95%CI = 1.051-1.279, P = 0.003)

¹This table provides an overview of studies investigating the role of various minerals (magnesium, calcium, zinc, iron, selenium) and omega-3 fatty acids in epilepsy and seizure disorders.

MDFA: Methyl-D-aspartate; OR: Odds ratio; TLE: Temporal lobe epilepsy.