Vitamin E, Alpha-Tocopherol, and Its Effects on Depression and Anxiety: A Systematic Review and Meta-Analysis

Nutrients
Q1
Feb 2022
Citations:53
Influential Citations:0
Systematic Reviews / Meta-Analyses
86
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Methods
Systematic review and meta-analysis of randomized controlled trials. Participants included adults with depression and/or anxiety or at risk for these conditions, across diverse populations (postpartum/perinatal, menopausal/syndromes like PCOS, elderly/geriatric, diabetes with depressive/anxiety symptoms, hepatitis C undergoing therapy, mild cognitive impairment with depressive symptoms, tardive dyskinesia, etc.). Study designs were randomized controlled trials; several were double- or triple-blind and placebo-controlled. Twelve trials were included; nine contributed data to meta-analyses for depression and anxiety.
Intervention
Regimens across included randomized trials (oral supplements): - Rees 2008: Vitamin E 80 mg/day (divided doses) in Sunola Oil (6 g total) containing DHA 27.3%, EPA 6.9%, omega-6 3.3%; 6 weeks. - Radzinskii 2016: Amberen containing tocopheryl acetate (Vitamin E); 2 capsules daily for 90 days. - Jamilian 2018: Vitamin E 400 IU/day + omega-3 fatty acids 1000 mg/day for 12 weeks. - Ataei-Almanghadim 2020: Vitamin E 200 IU/day in curcumin + vitamin E regimen; 8 weeks (oral capsules). - Tolonen 1985: Vitamin E (d-alpha-tocopherol) 400 mg per dose, twice daily (800 mg/day) for 1 year, with selenium constituents (sodium selenate and Vita-hiven selenium yeast per protocol). - Carlsson 2002: Vitamin E (tocopherol) 400 IU nightly for 6 months (co-administered with pravastatin). - Lohr 1988: Alpha-tocopherol 400 IU once daily in week 1; 800 IU/day in week 2; 1200 IU/day in weeks 3–4; duration 10 weeks. - Mazloom 2013: Vitamin E 400 IU/day + Vitamin C 1000 mg/day for 6 weeks. - Malaguarnera 2016: Silybin 94 mg + Vitamin E 30 mg + phospholipids 194 mg; three times daily for 12 months. - Lu 2009: Vitamin E 2000 IU/day; co-administered with donepezil; duration 3 years. - Adler 1999: Vitamin E 1600 IU/day; duration 2 years. - Meyer 2013: Vitamin E 10 mg/day + DHA 250 mg and EPA 70 mg per day (via 8 × 1 g capsules); 16 weeks.
Results
Vitamin E supplementation shows inconclusive results for depression and anxiety overall. Depression data (n=354 across 9 RCTs) favored Vitamin E (SMD −0.88; 95% CI −1.54 to −0.21; I2 = 87%), while anxiety data (n=306 across 3 RCTs) did not reach statistical significance (SMD −0.86; 95% CI −2.11 to 0.40; I2 = 95%). High heterogeneity and frequent co-supplement use (e.g., omega-3s, curcumin, silybin) limit clarity. The safety profile appears reassuring and Vitamin E is low-cost, but larger, high-quality trials using pure Vitamin E (without other constituents) are needed to establish efficacy for depression and anxiety. Some subgroups and co-supplement contexts (notably omega-3 co-supplementation) may show promise, but evidence is not definitive.
Limitations
Heterogeneous regimens (Vitamin E alone vs with omega-3s, curcumin, silybin, etc.); small to modest sample sizes in many trials; long durations and diverse populations; use of different outcome measures for mood/anxiety; several trials included additional active constituents, complicating attribution to Vitamin E; risk of bias varied across studies (some concerns, one high risk). Language restriction (English translations only) and potential publication bias in the included literature.

Abstract

Background: Recently, it has been discovered that anti-inflammatory and anti-oxidative pathways play a role in depression and anxiety. Lower serum levels of antioxidants, such as vitamin E, have been implicated in both depression and anxiety. Methods...