How is Vitamin K produced?

The vitamin K, just like vitamins A, D, and E, is fat-soluble in nature. Vitamin K1 is the primary form of vitamin K in cosmetics. It is found in the green leaves of vegetables. Indeed, in nature, vitamin K1 is synthesized by plants during photosynthesis. However, the concentrations obtained from plants are too low to use this method on a large scale, and the safety (absence of impurities) of the products would not be sufficiently controlled. In order to incorporate it into cosmetic formulations and fully benefit from its properties, it must be produced industrially, and currently, vitamin K1 is produced in a synthetic manner. Here are the major steps.

• Selection of Precursors. The synthesis of Vitamin K1 typically begins with basic chemical compounds that serve as precursors. These may include derivatives of naphthoquinone and other organic compounds. The main one used is the menadione (Vitamin K3), which is synthesized by the oxidation of 2-methylnaphthalene. Therefore, it is a synthetic precursor of Vitamin K1.

• Condensation. The precursors undergo condensation reactions, where multiple molecular fragments are combined to form a more complex structure. Firstly, to avoid undesirable reactions during the condensation stage, menadione is reduced to menadiol. The condensation occurs between a menadiol monoester and isophytol, a known intermediate in the synthesis reaction of vitamin K. This reaction is catalyzed by heat and an acid, typically boron trifluoride etherate.

• Saponification. In the synthesis of Vitamin K1, saponification is used to remove the protective groups added to the chemical precursors, through the use of a strong base. This chemical reaction breaks the protective bonds, thereby exposing the functional groups necessary for the subsequent stages of Vitamin K1 synthesis.

• Oxidation. The saponification product will be oxidized with a catalyst, such as silver oxide or air, to form the chemical bonds necessary for achieving the final structure of Vitamin K1.

• Purification. Finally, the reaction product is purified using various methods, such as crystallization, to remove unwanted compounds and obtain a pure version of Vitamin K1.

The commercial process of chemical synthesis of Vitamin K1 has remained virtually unchanged since its publication in 1939. This is primarily due to the low cost and immediate availability of raw materials.

However, this process also presents a significant drawback. The catalysts and solvents used are harmful to both humans and the environment.

It's important to note that vitamin K1 has recently been banned for use in cosmetics in Europe. According to the European Commission Directive 2009/6/EC of February 4, 2009, and after consultation with the Scientific Committee on Consumer Products (SCCP), it was decided that the pure use of phytonadione (vitamin K1) in cosmetics is not safe due to the risks of skin allergy, photo-instability, and sensitization to vitamin K.

For this reason, cosmetic manufacturers today use the oxidized version of vitamin K1, the vitamin K1 oxide. It is said to be less irritating and more stable in light. It is produced by adding an oxidation step, which can be carried out at different stages of the vitamin K1 synthesis process. For example, it can be performed after the condensation step of the precursors to form the naphthoquinone core, or after hydrogenation to saturate the unsaturated bonds, or even at the very end of the process, after the purification of the final product.