Home Ingredients E-TPGS (Water-Soluble Vitamin E)
Antioxidant

E-TPGS (Water-Soluble Vitamin E)

Evidence Level
Preliminary
0 Clinical Trials
4 Documented Benefits
1/5 Evidence Score

E-TPGS (d-alpha-tocopheryl polyethylene glycol succinate) is a water-soluble form of natural vitamin E. It serves both as a source of antioxidant vitamin E and as an absorption enhancer that improves the uptake of fat-soluble nutrients. Its main role is as a delivery form rather than a stand-alone studied supplement. The human evidence on E-TPGS itself cited on this page comes from children with chronic cholestasis, in whom it restored vitamin E levels but, in the one small study that checked, did not lower a lipid peroxidation marker, and from seven patients with ultra-rare inherited fat-malabsorption disorders. In that second study the water-soluble form was better absorbed in one subgroup, but the two vitamin E formulations produced similar outcomes after four months. The other references are pharmaceutical formulation science about drug delivery and a dose-ranging trial of plain vitamin E in adults with high cholesterol. No cited study looked at a healthy person taking E-TPGS as a supplement.

Studied Dose Per the product or formulation; no supplemental dose has been established for healthy people.
Active Compound d-alpha-tocopheryl polyethylene glycol 1000 succinate (water-soluble vitamin E).

Benefits

Vitamin E source

E-TPGS provides natural-source vitamin E (alpha-tocopherol) in a water-soluble form. Vitamin E is the body's main fat-soluble antioxidant, so the antioxidant classification on this page rests on what the molecule is, a vitamin E derivative. The one cited E-TPGS study that measured a lipid peroxidation marker, in 15 children with cholestasis, found no change.

Absorption enhancement

E-TPGS is used to improve the absorption of vitamin E and other fat-soluble compounds, and it is the vitamin E form used clinically when fat absorption is impaired, as in cholestasis, cystic fibrosis and rare inherited fat-malabsorption disorders. That is a real but narrow clinical use. The supporting evidence is pharmaceutical formulation research, a multicenter study in 60 children with cholestasis, and one crossover study in seven patients. In that study the water-soluble form reached higher bioavailability in the four patients with chylomicron retention disease, but after four months of treatment the two vitamin E formulations produced similar outcomes. Nothing cited here tests whether this absorption advantage does anything for a person who absorbs fat normally.

Delivery-form note

Its primary role is as a water-soluble delivery form and absorption enhancer rather than a separately studied health supplement. It normally appears as one component of a formula at an amount chosen by the formulator, and in the pharmaceutical literature the endpoint being measured is usually the delivery of the substance it carries rather than an effect of E-TPGS itself.

Restores antioxidant vitamin E levels when fat absorption is poor

Tested as E-TPGS itself: in 60 children with chronic cholestasis who had not responded to other oral vitamin E, 20 to 25 IU/kg a day normalized vitamin E status in all of them. In a small study of 15 such children, blood vitamin E rose but a lipid peroxidation marker (TBARS) did not fall. With plain alpha-tocopherol in adults with high cholesterol, a peroxidation marker fell significantly only at 1,600 IU a day or more.

Mechanism of action

1

Antioxidant vitamin E activity

Once delivered, alpha-tocopherol protects cell membranes from lipid peroxidation as the body's main fat-soluble antioxidant. This is established vitamin E biochemistry; in the one E-TPGS study that measured it, a blood lipid peroxidation marker did not fall.

2

Micelle-forming absorption

The polyethylene glycol portion makes vitamin E water-dispersible, forming micelles that improve uptake of fat-soluble nutrients.

Clinical trials

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated at normal vitamin E intakes. The safety concerns below attach to high-dose vitamin E, not to the small amounts used as a delivery aid.
Very high vitamin E doses can increase bleeding risk. Two further findings concern high-dose vitamin E generally, which is the family this ingredient belongs to. A meta-analysis of vitamin E supplementation trials linked doses of 400 IU per day or more with an increase in all-cause mortality. The large SELECT trial found a significant increase in prostate cancer incidence in healthy men taking 400 IU per day of vitamin E. Do not take high-dose vitamin E without medical advice.
Discontinue if any unusual reaction occurs.

Important Drug interactions

Anticoagulants (warfarin) — high-dose vitamin E may add to bleeding risk; monitor.
May enhance absorption of fat-soluble drugs; tell your doctor. TPGS is used in pharmaceuticals precisely because it raises drug absorption, partly by inhibiting the P-glycoprotein efflux pump, so it can raise blood levels of medicines taken alongside it. This matters most for drugs with a narrow safe dose range.
Stop high-dose vitamin E before surgery, per your doctor.

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Frequently asked questions about E-TPGS (Water-Soluble Vitamin E)

What is E-TPGS?

E-TPGS (d-alpha-tocopheryl polyethylene glycol succinate) is a water-soluble form of natural vitamin E. It serves both as a source of antioxidant vitamin E and as an absorption enhancer that improves the uptake of fat-soluble nutrients. Its main role is as a delivery form rather than a stand-alone studied supplement.

What is E-TPGS used for?

E-TPGS is researched primarily for Antioxidant. E-TPGS provides natural-source vitamin E (alpha-tocopherol) in a water-soluble form. Vitamin E is the body's main fat-soluble antioxidant, so the antioxidant classification on this page rests on what the molecule is, a vitamin E derivative.

What is the recommended dosage of E-TPGS?

The clinically studied dose is Per the product or formulation; no supplemental dose has been established for healthy people. Always follow the product label and check with a healthcare provider for personal advice.

Is E-TPGS safe, and does it have side effects?

Side effects and cautions reported for E-TPGS include: Generally well-tolerated at normal vitamin E intakes. The safety concerns below attach to high-dose vitamin E, not to the small amounts used as a delivery aid. Very high vitamin E doses can increase bleeding risk. It may also interact with some medications. E-TPGS is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does E-TPGS interact with any medications?

Possible interactions include: Anticoagulants (warfarin) — high-dose vitamin E may add to bleeding risk; monitor. May enhance absorption of fat-soluble drugs; tell your doctor. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for E-TPGS?

NutraSmarts rates the evidence for E-TPGS as Preliminary (1 out of 5). It is backed by 5 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(5 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Guo Y, Luo J, Tan S, Otieno BO, Zhang Z The applications of Vitamin E TPGS in drug delivery European Journal of Pharmaceutical Sciences. 2013;49(2):175-186. doi:10.1016/j.ejps.2013.02.006.PubMedUsed to support: Review of pharmaceutical formulation science. It describes vitamin E TPGS as an excipient used to solubilize drugs, improve their absorption and inhibit the P-glycoprotein efflux pump involved in drug resistance. It supports the claim that TPGS enhances absorption of substances formulated with it. It is not a study of a health benefit in people, it reports no clinical outcome, and its subject is drug delivery rather than nutrient supplementation.
  2. Cuerq C, Henin E, Restier L, Blond E, Drai J, Marçais C, Di Filippo M, Laveille C, Michalski MC, Poinsot P, Caussy C, Sassolas A, Moulin P, Reboul E, Charriere S, Levy E, Lachaux A, Peretti N Efficacy of two vitamin E formulations in patients with abetalipoproteinemia and chylomicron retention disease Journal of Lipid Research. 2018;59(9):1640-1648. doi:10.1194/jlr.M085043.PubMedUsed to support: Crossover study in seven patients in total: three with abetalipoproteinemia and four with chylomicron retention disease, both extremely rare inherited recessive disorders of fat absorption. It compared tocofersolan, the water-soluble vitamin E form that is this page's molecule, against alpha-tocopherol acetate, using a single dose and then four months of treatment. Bioavailability was higher with the water-soluble form in the chylomicron retention disease patients, but the two formulations gave similar outcomes at four months. It involved neither healthy people nor any antioxidant endpoint.
  3. Sokol RJ, Butler-Simon N, Conner C, Heubi JE, Sinatra FR, Suchy FJ, Heyman MB, Perrault J, Rothbaum RJ, Levy J, et al. Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology. 1993;104(6):1727-1735. doi:10.1016/0016-5085(93)90652-s.PubMedUsed to support: Multicenter trial in 60 vitamin E-deficient children with chronic cholestasis who had not responded to 70 to 212 IU/kg/day of other oral vitamin E. Oral TPGS (started at 25 IU/kg/day) normalized vitamin E status in all of them. Neurological function improved in 25, stabilized in 27 and worsened in 2 over a mean of 2.5 years. It shows E-TPGS delivers vitamin E when fat absorption is impaired. It is not an antioxidant-outcome study.
  4. Socha P, Koletzko B, Pawlowska J, Proszynska K, Socha J Treatment of cholestatic children with water-soluble vitamin E (alpha-tocopheryl polyethylene glycol succinate): effects on serum vitamin E, lipid peroxides, and polyunsaturated fatty acids. J Pediatr Gastroenterol Nutr. 1997;24(2):189-193. doi:10.1097/00005176-199702000-00013.PubMedUsed to support: Small within-group study in 15 cholestatic children switched to oral TPGS at 20 IU/kg once daily. Serum alpha-tocopherol rose significantly by 1 month and further by 1 year. Plasma lipid peroxides (TBARS), which were raised versus controls, did not change significantly. Backs the null peroxidation statement in the Antioxidant benefit.
  5. Roberts LJ 2nd, Oates JA, Linton MF, Fazio S, Meador BP, Gross MD, Shyr Y, Morrow JD The relationship between dose of vitamin E and suppression of oxidative stress in humans. Free Radic Biol Med. 2007;43(10):1388-1393. doi:10.1016/j.freeradbiomed.2007.06.019.PubMedUsed to support: Dose-ranging trial of plain RRR-alpha-tocopherol (not E-TPGS) at 0 to 3200 IU/day for 16 weeks in adults with polygenic hypercholesterolemia. Plasma F2-isoprostanes, a lipid peroxidation marker, fell significantly only at 1600 IU (35%) and 3200 IU (49%). Backs the high dose threshold stated in the Antioxidant benefit.