Tocopherol (vitamin E)

One of the most well-known and researched antioxidants for the body and for skin. Vitamin E occurs naturally in human skin, but can become depleted due to constant environmental exposure in the absence of sun protection.

Physical Characteristics

There are 8 different derivatives of Vitamin E and α-tocopherol is the most bioavailable form of Vitamin E in tissues. The most typical forms are d-alpha-tocopherol, d-alpha-tocopherol acetate, dl-alpha tocopherol, and dl-alpha tocopherol acetate.

Not synthesised within the body: it is an essential nutrient that must be ingested or applied topically
Readily depleted by UVR exposure
Molecular weight of α-tocopherol: 431 Daltons
Very lipophillic compound
Insoluble in water
Commonly found in an oil base

Mechanism of Actions

Antioxidant and Photoprotective:

The major form of Vitamin E found in human tissues is α-tocopherol, which is a powerful lipophilic antioxidant
Works as an antioxidant by donating electrons to free radicals, reducing them
As the major lipophilic antioxidant in human tissues it protects the skin from lipid peroxidation and oxidative damage induced by ROS and UV exposure
Reduces the incidence and severity of UVR induced erythema, inflammation, sunburn cell formation, DNA damage, photocarcinogenesis and immunosuppression
Must be applied prior to sun exposure to be most effective

Synergistic photoprotective effect with Vitamin C

Anti-inflammatory:

UVR generates inflammation through ROS and cytokines and other inflammatory mediators
Through its antioxidant action it can reduce the inflammatory response induced by UVR exposure
Reduces levels of PGE2 and nitric oxide
Inhibits cyclooxygenase-2 (COX-2) enzyme mRNA that is responsible for oxidative stress induced inflammation

Reduces Collagen Breakdown:

α-tocopherol reduces MMP-1 transcription slowing the process of collagen breakdown

Maintains the stability and integrity of the intercellular membrane:

Improves the skin barrier function, hence enhances skin hydration by decreasing TEWL

Regulates keratin turnover

a-tocopherol acetate has antibacterial properties:

Lowers the pH of the wound bed and creates an anhydrous environment
Has been used in wound healing dressings on infected wounds in an oil based

Clinical Indicators

Wound healing
Photoageing
UVR and environmental exposure
Inflammatory conditions
Dry and dehydrated skin
Poor barrier function
Sunburn

Metabolism And Excretion

Once applied topically, α-tocopherol penetrates the skin and is located within the lipid bilayer
The highest levels are located within the lower stratum corneum
As non-bioactive ester forms are used more commonly in cosmeceutical formulations, they must be converted via hydrolysis to α-tocopherol to become bioactive first
This is where is acts as an antioxidant protecting against lipid peroxidation
Once α-tocopherol is oxidised, it can be regenerated by L-ascorbic acid and lipoic acid in tissues following antioxidant activity

Formulation Considerations

1-5% concentrations have been found to be effective
Transdermal delivery of a-tocopherol is challenging due to it being very lipophilic and insoluble in water
Due to its’s lipophilic nature and large molecular weight, a large percentage of a-tocopherol can be deposited into the stratum corneum with a lower penetration rate to viable tissues
Use of solvent penetration enhancers such as ethanol and surfactants can enhance a-tocopherol penetration
α-tocopherol can be unstable in solution and is often included in an ester form

α-tocopherol acetate:

A prodrug ester derivative of α-tocopherol that is not biologically active
Converts into α-tocopherol in tissues via hydrolysis, which is the bioactive form
As it has to be bio-converted it is not as effective as α-tocopherol in tissues