Tocopherol

Identification

Generic Name

Tocopherol

DrugBank Accession Number

DB11251

Background

Tocopherol exists in four different forms designated as α, β, δ, and γ. They present strong antioxidant activities, and it is determined as the major form of vitamin E. Tocopherol, as a group, is composed of soluble phenolic compounds that consist of a chromanol ring and a 16-carbon phytyl chain. The classification of the tocopherol molecules is designated depending on the number and position of the methyl substituent in the chromanol ring. The different types of tocopherol can be presented trimethylated, dimethylated or methylated in the positions 5-, 7- and 8-. When the carbons at position 5- and 7- are not methylated, they can function as electrophilic centers that can trap reactive oxygen and nitrogen species. Tocopherols can be found in the diet as part of vegetable oil such as corn, soybean, sesame, and cottonseed.¹ It is currently under the list of substances generally recognized as safe (GRAS) in the FDA for the use of human consumption.¹⁰

Type

Small Molecule

Groups

Approved, Investigational

Synonyms

• Methyltocols
• tocoferol
• tocoferoles
• tocophérol
• Tocopherols

External IDs

• E-306
• E-MIX 80

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Pharmacology

Indication

Tocopherol can be used as a dietary supplement for patients with a deficit of vitamin E; this is mainly prescribed in the alpha form.³ Vitamin E deficiency is rare, and it is primarily found in premature babies of very low birth weight, patients with fat malabsorption or patients with abetalipoproteinemia.¹¹

Tocopherol, due to its antioxidant properties, is studied for its use in prevention or treatment in different complex diseases such as cancer,¹ atherosclerosis, cardiovascular diseases,² and age-related macular degeneration.⁴

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Vitamin e deficiency		••••••••••••			•••••••

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Associated Therapies

• Skin Care

Contraindications & Blackbox Warnings

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Pharmacodynamics

The antioxidant effects of tocopherol can be translated into different changes at the pharmacodynamic level. In vitro studies have shown that this antioxidant activity can produce modification in protein kinase C (PKC) which will later be translated into an inhibition of cell death. Some other derivate effects are the anti-inflammatory properties of tocopherol which can be related to the modulation of cytokines or prostaglandins, prostanoids and thromboxanes.⁵

Mechanism of action

Tocopherol acts as a radical scavenger. It mainly acts as an antioxidant for lipid bilayers. Tocopherol's functions depend on the H-atom donating ability, location, and movement within the membrane, as well as the efficiency in the radical recycling by some cytosolic reductants such as ascorbate.⁵ Tocopherol actions are related to the trap of radicals, and it has been shown that even in the absence of substituents in the ortho-positions, tocopherol can trap more than two radicals. The type of radicals available for tocopherol are alkyl and peroxy.¹²

Target	Actions	Organism
AFree radicals	binder	Humans

Absorption

The absorption of tocopherol in the digestive tract requires the presence of fat.¹¹ The bioavailability of tocopherols is highly dependent on the type of isomer that is administered where the alpha-tocopherol can present a bioavailability of 36%. This isomer specificity also determines the intestinal permeability in which the gamma-tocopherol presents a very low permeability. After oral administration, the C_max was 1353.79 ng/ml for δ-tocopherol, 547.45 ng/ml for γ-tocopherol, 704.16 ng/ml for β-tocopherol, and 2754.36 ng/ml for α-tocopherol. The T_max is three to four hours for δ-tocopherol, γ-tocopherol, and β-tocopherol and about six hours for α-tocopherol.⁶

Volume of distribution

The apparent volume of distribution was 0.284 ± 0.021 mL for δ-tocopherol, 0.799 ± 0.047 mL for γ-tocopherol, and 0.556 ± 0.046 mL for β-tocopherol.⁶

Protein binding

There has not been described a specific plasma transport protein for tocopherol but it is thought that it is highly bound to lipoproteins such as VLDL, HDL and chylomicrons.⁸

Metabolism

Excess tocopherol is converted into their corresponding carboxyethylhydroxychroman (CEHC), based on the isomer of tocopherol.⁷ More deeply, the metabolism of tocopherol begins with the hepatic metabolism which is led by a CYP4F2/CYP3A4-dependent ω-hydroxylation of the side chains which leads to the formation of 13'-carboxychromanol. The metabolic pathway is followed by five cycles of β-oxidation. The β-oxidation cycles function by shortening the side chains, the first cycle results in the formation of carboxydimethyldecylhydroxychromanol followed by carboxymethyloctylhydroxychromanol. These two metabolites are categorized as long-chain metabolites and they are not excreted in the urine. Some intermediate-chain metabolites that are products of two rounds of β-oxidation are carboxymethylhexylhydroxychromanol and carboxymethylbutylhydroxychromanol. These intermediate-chain metabolites can be found in human feces and urine. The catabolic end-product of tocopherols, as stated before, is CEHC which can be largely found in urine and feces.⁸

Two new metabolites have been detected in human and mice feces. These new metabolites are 12'-hydroxychromanol and 11'-hydroxychromanol. Because of their chemistry, it is thought that these metabolites can be the evidence for a ω-1 and ω-2 hydroxylation which leads to an impaired oxidation of 12'-OH followed side-chain truncation.⁸

Hover over products below to view reaction partners

• Tocopherol
  • 13'-hydroxychromanol
    • 13'-carboxychromanol
      • CDMDHC
        • CDMOHC
          • CDMHHC
            • CMBHC
              • CEHC

Route of elimination

The pharmacokinetic profile of tocopherol indicates a longer time of excretion for tocopherols when compared to tocotrienols.⁶ The different conjugated metabolites are excreted in the urine or feces depending on the length of their side-chain.⁷ Due to their polarity, intermediate-chain metabolites and short-chain metabolites are excreted via urine as glucoside conjugates. A mixture of all the metabolites and precursors can be found in feces. The long-chain metabolites correspond to >60% of the total metabolites in feces. It is estimated that the fecal excretion accounts for even 80% of the administered dose.⁸

Half-life

The elimination half-life ranged from 2.44 to 3.02 hours for δ-tocopherol, γ-tocopherol, and β-tocopherol.⁶

Clearance

Clearance ranged from 0.081 to 0.190 L/h for δ-tocopherol, γ-tocopherol, and β-tocopherol.⁶

Adverse Effects

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Toxicity

Tocopherols are considered as non-toxic but if very high doses are administered, there are reports of hemorrhagic activity. Reproductive and developmental toxicity tests are negative. These negative results were also observed in the analysis of mutagenicity and carcinogenicity.⁹

Pathways

Not Available

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Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Integrate drug-drug interactions in your software
Abacavir	Abacavir may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Abametapir	The serum concentration of Tocopherol can be increased when it is combined with Abametapir.
Aceclofenac	Aceclofenac may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Tocopherol which could result in a higher serum level.
Acetaminophen	Acetaminophen may decrease the excretion rate of Tocopherol which could result in a higher serum level.

Food Interactions

No interactions found.

Products

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Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Conju Princess	Soap	1.1 g/100g	Topical	Conju Inc	2015-12-25	Not applicable
Conju Princess Cleansing Balm	Cream	0.0032 g/100g	Topical	Conju Inc	2016-03-14	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Aloe Vera Sprayer	Tocopherol (0.5 g/100g) + Aloe vera leaf (2 g/100g) + Glycerin (4 g/100g) + Propylene glycol (2 g/100g)	Liquid	Topical	NINGBO JIANGBEI OCEAN STAR TRADING CO.,LTD	2015-02-20	Not applicable
bdr Laser Effect Peptide Complex Face Mask	Tocopherol (0.105 g/30g) + Hyaluronic acid (0.51 g/30g)	Patch	Topical	Hanaim International Llc	2016-11-22	Not applicable
Calming Skin	Tocopherol (0.65 g/130mL) + Glycerin (0.65 g/130mL) + Panthenol (0.65 g/130mL)	Lotion	Topical	Atomy Co., Ltd.	2011-07-18	2017-12-01
Calming Skin	Tocopherol (0.65 mL/130mL) + Glycerin (0.65 mL/130mL) + Panthenol (0.65 mL/130mL)	Lotion	Topical	ATOMY CO LTD	2011-06-22	2011-06-22
Disinfect Wipes	Tocopherol (0.0025 1/1001) + Aloe vera leaf (0.0025 1/1001) + Benzalkonium chloride (0.4 1/1001) + Cetylpyridinium chloride (0.03 1/1001) + Citric acid (0.01 1/1001) + Didecyldimethylammonium chloride (0.2 1/1001) + Dimethicone (0.05 1/1001) + Glycerin (0.01 1/1001) + Phenoxyethanol (0.2 1/1001)	Cloth	Topical	Jiangsu Terra Medical Technology Co Ltd	2020-03-30	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
bdr Laser Effect Peptide Complex Face Mask	Tocopherol (0.105 g/30g) + Hyaluronic acid (0.51 g/30g)	Patch	Topical	Hanaim International Llc	2016-11-22	Not applicable
Calming Skin	Tocopherol (0.65 g/130mL) + Glycerin (0.65 g/130mL) + Panthenol (0.65 g/130mL)	Lotion	Topical	Atomy Co., Ltd.	2011-07-18	2017-12-01
Calming Skin	Tocopherol (0.65 mL/130mL) + Glycerin (0.65 mL/130mL) + Panthenol (0.65 mL/130mL)	Lotion	Topical	ATOMY CO LTD	2011-06-22	2011-06-22
Ciclopirox	Tocopherol (50 mg/1) + Ciclopirox (80 mg/1mL)	Kit	Topical	Acella Pharmaceuticals, LLC	2008-10-27	2015-05-31
Conju Princess	Tocopherol (1.1 g/100g)	Soap	Topical	Conju Inc	2015-12-25	Not applicable

Categories

ATC Codes

A11HA03 — Tocopherol (vit e)

• A11HA — Other plain vitamin preparations
• A11H — OTHER PLAIN VITAMIN PREPARATIONS
• A11 — VITAMINS
• A — ALIMENTARY TRACT AND METABOLISM

Drug Categories

• Alimentary Tract and Metabolism
• Antioxidants
• Benzopyrans
• Biological Factors
• Compounds used in a research, industrial, or household setting
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Substrates
• Diet, Food, and Nutrition
• Drugs that are Mainly Renally Excreted
• Food
• Heterocyclic Compounds, Fused-Ring
• Micronutrients
• Physiological Phenomena
• Protective Agents
• Pyrans
• Vitamin E
• Vitamins
• Vitamins (Fat Soluble)

Classification

Not classified

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

R0ZB2556P8

CAS number

1406-66-2

References

General References

1. Das Gupta S, Suh N: Tocopherols in cancer: An update. Mol Nutr Food Res. 2016 Jun;60(6):1354-63. doi: 10.1002/mnfr.201500847. Epub 2016 Feb 2. [Article]
2. Mathur P, Ding Z, Saldeen T, Mehta JL: Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease. Clin Cardiol. 2015 Sep;38(9):570-6. doi: 10.1002/clc.22422. Epub 2015 Aug 14. [Article]
3. Kim HJ, Giovannucci E, Rosner B, Willett WC, Cho E: Longitudinal and secular trends in dietary supplement use: Nurses' Health Study and Health Professionals Follow-Up Study, 1986-2006. J Acad Nutr Diet. 2014 Mar;114(3):436-43. doi: 10.1016/j.jand.2013.07.039. Epub 2013 Oct 9. [Article]
4. Chew EY, Clemons TE, Agron E, Sperduto RD, Sangiovanni JP, Kurinij N, Davis MD: Long-term effects of vitamins C and E, beta-carotene, and zinc on age-related macular degeneration: AREDS report no. 35. Ophthalmology. 2013 Aug;120(8):1604-11.e4. doi: 10.1016/j.ophtha.2013.01.021. Epub 2013 Apr 10. [Article]
5. Traber MG, Atkinson J: Vitamin E, antioxidant and nothing more. Free Radic Biol Med. 2007 Jul 1;43(1):4-15. doi: 10.1016/j.freeradbiomed.2007.03.024. Epub 2007 Mar 31. [Article]
6. Qureshi AA, Khan DA, Silswal N, Saleem S, Qureshi N: Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans. J Clin Exp Cardiolog. 2016 Apr;7(4). doi: 10.4172/2155-9880.1000434. Epub 2016 Apr 28. [Article]
7. Brigelius-Flohe R, Traber MG: Vitamin E: function and metabolism. FASEB J. 1999 Jul;13(10):1145-55. [Article]
8. Schmolz L, Birringer M, Lorkowski S, Wallert M: Complexity of vitamin E metabolism. World J Biol Chem. 2016 Feb 26;7(1):14-43. doi: 10.4331/wjbc.v7.i1.14. [Article]
9. Zondlo Fiume M: Final report on the safety assessment of Tocopherol, Tocopheryl Acetate, Tocopheryl Linoleate, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl Tocopheryl Methylsilanol, Potassium Ascorbyl Tocopheryl Phosphate, and Tocophersolan. Int J Toxicol. 2002;21 Suppl 3:51-116. doi: 10.1080/10915810290169819. [Article]
10. FDA Code of Federal Regulations [Link]
11. National Institute for Health [Link]
12. Researchgate [Link]

External Links

PubChem Substance

347911165

RxNav

1236136

Wikipedia

Tocopherol

MSDS

Download (1.3 MB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Prevention	Colon Cancer	1
4	Completed	Treatment	Lymphedema Lower Extremity	1
4	Completed	Treatment	Osteoradionecrosis	1
4	Recruiting	Treatment	Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD	1
3	Completed	Prevention	Glaucoma	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Liquid	Topical
Patch	Topical
Lotion	Topical
Injection, powder, for solution	Intravenous
Kit	Topical
Soap	Topical	1.1 g/100g
Cream	Topical	0.0032 g/100g
Capsule
Tablet
Tablet, coated
Injection, solution	Intramuscular
Pill
Solution / drops	Oral
Liquid	Oral
Capsule, gelatin coated; kit; tablet	Oral
Capsule, gelatin coated	Oral
Capsule	Oral
Gum, chewing	Oral
Capsule		200 U.I.
Capsule		400 U.I.
Cloth	Topical
Emulsion	Topical
Capsule, coated	Oral
Solution	Topical
Tablet, coated	Oral
Gel
Capsule

Prices

Not Available

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
boiling point (°C)	Decomposes	'MSDS'
water solubility	Insoluble	'MSDS'

Predicted Properties

Not Available

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

Targets

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1. Free radicals

Kind

Group

Organism

Humans

Pharmacological action

Yes

Actions

Binder

References

1. Traber MG, Atkinson J: Vitamin E, antioxidant and nothing more. Free Radic Biol Med. 2007 Jul 1;43(1):4-15. doi: 10.1016/j.freeradbiomed.2007.03.024. Epub 2007 Mar 31. [Article]

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Drug created at December 03, 2015 16:51 / Updated at April 09, 2022 11:39