How is Vitamin E obtained?

The vitamin E is a natural active ingredient first identified in 1922 by Herbert EVANS and Katharine BISHOP. Following studies conducted on rats, these scientists hypothesized the existence of a lipophilic compound essential for fetal development. Two years later, Bennett SURE confirmed this hypothesis and showed that the absence of this compound in the diet of rats caused their sterility. It was then named vitamin E, as the other letters were already taken. It also received the name of tocopherol, from the Greek tokos: offspring and pherein: to bear. The story of vitamin E continues in 1936 when it was first isolated from wheat germ oil by Herbert EVANS and Oliver EMERSON. Its structure was finally determined in 1938 by Erhard FERNHOLZ.

Vitamin E actually refers to a group of eight fat-soluble molecules, meaning they dissolve in fats: 4 tocopherols and 4 tocotrienols. For stability reasons, alpha-tocopherol is the most commonly used form of Vitamin E in cosmetic products.

Today, the majority of the vitamin E found in cosmetic products is extracted from vegetable oils. For this process, one or more oils can be used. Most commonly, these are soybean oil and/or sunflower oil, which are very rich in tocopherols. The extraction is carried out using an organic solvent, in which the non-saponifiable elements of vegetable oils, such as vitamin E, are soluble, while the fatty acids, glycerol, and other hydrophilic compounds remain in the aqueous alkaline phase. The most frequently used solvent is hexane, either alone or with a small fraction of a more polar solvent such as ethanol, ethyl acetate, or diisopropyl ether. It is also possible to use acetone, diethyl ether, or a 2:1 mixture of chloroform-methanol. In the latter case, this is referred to as Folch extraction.

The extraction of vitamin E from vegetable oils is typically carried out using a vortex or similar stirring systems . These devices allow for vigorous yet controlled agitation of the solution, which reduces the extraction time. The solvent is then evaporated using a rotary evaporator under reduced pressure. The temperature depends on the solvent used but is often within ranges between 40 and 60°C. Afterward, the extracted vitamin E undergoes various purification processes to remove impurities and obtain a purer molecule. Distillation, filtration, and decantation steps are notably involved. Throughout the process, the quality of the vitamin E is tested by several chromatography methods (HPLC, TLC, CEC...).

It is also possible to synthesize vitamin E in a laboratory. However, this method is being used less and less due to its cost and technical complexity. Here are the main steps of this chemical synthesis, noting however that these may slightly vary from one laboratory to another.

1. Formation of the chromanol ring.

   The first step in the synthesis of alpha-tocopherol involves hydroquinone, an aromatic compound also known as 1,4-benzenediol, and isophytol, a natural precursor of tocopherols derived from phytol, a component of plant chlorophyll. These two molecules react together to form a chromanol ring, the fundamental structure of vitamin E.

2. Alkylation of the Chromanol Ring.

   Once formed, the chromanol ring must be alkylated to introduce the isoprenoid side chains. Among the intermediates commonly used to carry out this reaction, we can mention geranylgeranyl pyrophosphate.

3. Hydroxylation and Methylation.

   In conclusion, successive hydroxylation/methylation reactions are performed to establish the alcohol group of alpha-tocopherol as well as its carbon chain.

4. Purification and Isolation.

   Once the reactions are completed, alpha-tocopherol is purified and isolated using chromatography techniques such as high-performance liquid chromatography, thin-layer chromatography, or size-exclusion chromatography. The goal is to obtain a product that is as pure as possible, free from reaction by-products.

• ISTASSE L. & al. Chemistry, Food Sources, and Dosage of Vitamin E. Annals of Veterinary Medicine (2003).

• NETSCHER T. Synthesis of Vitamin E. Vitamins & Hormones (2007).

• Dissertation by Mohammed GUIGA. Vitamin E: Metabolism, Physiological Role: Benefits and Risks of Supplementation (2021).

• ERKEKOGLU P., SANTOS S. & BLUMENBERG M. Vitamin E in Health and Disease: Interactions, Diseases and Health Aspects. Biochemistry (2021).