Vitamin E

Identified as a fat-soluble factor preventing fetal resorption in animals; later understood as a lipid-phase antioxidant protecting cell membranes from oxidative damage. In clinical practice, vitamin E is essential to treat deficiency states (e.g., fat-malabsorption, abetalipoproteinemia); routine high-dose supplementation for chronic-disease prevention is not supported by outcome trials.

Vitamin E is a family of eight compounds: four tocopherols (α, β, γ, δ) and four tocotrienols. Human requirement and labeling are expressed as mg α-tocopherol (the only form maintained in plasma via α-tocopherol transfer protein). Unit conversions: 1 IU natural (RRR-α-tocopherol) = 0.67 mg α-tocopherol; 1 IU synthetic (all-rac) = 0.45 mg α-tocopherol.

- Antioxidant: scavenges lipid peroxyl radicals, interrupting chain oxidation in PUFA-rich membranes and lipoproteins.

- Gene/expression effects: modulates cell signaling and inflammatory pathways (e.g., PKC), though clinical significance depends on context and dose.

1. Treatment of Vitamin E Deficiency

• Indicated in fat-malabsorption syndromes and rare genetic disorders (e.g., abetalipoproteinemia); dosing is individualized and often high under medical supervision. RDA (adults): 15 mg/day α-tocopherol; UL (U.S.): 1,000 mg/day (≈1,500 IU natural or 1,100 IU synthetic).

2. Age-Related Macular Degeneration (AMD) as part of AREDS/AREDS2

• The AREDS and AREDS2 formulas (which include vitamin E 400 IU/day alongside vitamin C, zinc, copper, and lutein/zeaxanthin in AREDS2) reduce the risk of progression from intermediate to late AMD; vitamin E alone is not effective. Use only in patients who meet AREDS criteria.

3. Nonalcoholic Steatohepatitis (NASH) selected patients

• In non-diabetic adults with biopsy-proven NASH, vitamin E 800 IU/day improved histology vs placebo in the PIVENS RCT; major liver societies allow consideration after discussing risks/benefits. Evidence in diabetes is less consistent and generally not recommended.

• History of hemorrhagic stroke or high bleeding risk / peri-operative period: avoid high doses due to increased risk of hemorrhagic stroke in meta-analysis of RCTs.

• Prostate-cancer risk in men considering high-dose supplements: SELECT found 400 IU/day synthetic α-tocopherol increased prostate-cancer incidence vs placebo. Avoid non-indicated high-dose use.

• Unsupervised use in pregnancy/children at high doses: stick to dietary intake unless clinician-directed.

Generally well tolerated at RDA-level intakes. High-dose supplementation 400 IU/day has been linked to hemorrhagic stroke risk and possible all cause mortality in some meta-analyses (methodological debates exist, but precaution is warranted). Symptoms can include easy bruising and GI upset

• Warfarin/DOACs/antiplatelets: high-dose vitamin E may increase bleeding (vitamin-K antagonism/platelet effects); monitor INR/bleeding closely or avoid non-essential high doses.

• Oncology regimens: antioxidant supplements (incl. vitamin E) around chemo/radiation remain controversial coordinate with the oncology team. (General guidance echoed by NIH ODS.)

• Statins/other cardiometabolic drugs: no consistent clinically meaningful PK interactions, but avoid using vitamin E in place of evidence-based therapies

1. Anti-inflammatory: https://pmc.ncbi.nlm.nih.gov/articles/PMC7011499/

2. Supports immune Function: https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/

3. Alzheimer's Disease: https://pmc.ncbi.nlm.nih.gov/articles/PMC6412423/

4. Cardiovascular health: https://pmc.ncbi.nlm.nih.gov/articles/PMC10692867/

5. Liver iron depletion: https://pmc.ncbi.nlm.nih.gov/articles/PMC10375508/

6. Vaginal Vitamin E for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review of Randomized Controlled Trials https://pmc.ncbi.nlm.nih.gov/articles/PMC9086347/#sec5

Vitamin E (α-tocopherol) is an essential fat-soluble antioxidant. Best-supported clinical uses are treating deficiency and specific indications such as AREDS/AREDS2 for intermediate AMD and 800 IU/day in carefully selected, non-diabetic adults with biopsy-proven NASH. Routine high-dose supplementation for chronic-disease prevention is not supported and may increase risks (hemorrhagic stroke; prostate-cancer signal; possible mortality signal at ≥400 IU/day). Keep intakes near the RDA (15 mg/day) unless medically indicated, observe ULs, and use caution with anticoagulants/antiplatelets or peri-operative care.