How is vitamin K manufactured?

November 18, 2025 •

4 min read

According to recent studies, microbial fermentation is emerging as a more sustainable industrial method for producing natural vitamin K compared to traditional chemical synthesis. This raises the question: how is vitamin K manufactured for widespread use in supplements and food fortification?

Quick Summary

Vitamin K is produced industrially through chemical synthesis for vitamin K1 and microbial fermentation for vitamin K2 (MK-7). Both methods involve complex multi-step processes, utilizing different raw materials and techniques to yield the final product for commercial use.

Key Points

Three Main Methods: Vitamin K is industrially produced via chemical synthesis for K1, microbial fermentation for K2, or natural extraction, with chemical synthesis and fermentation being the most common.
Chemical Synthesis for K1: This process typically uses menadione (Vitamin K3) as a precursor, involving condensation with isophytol and oxidation steps, but can generate impurities and uses harsh chemicals.
Microbial Fermentation for K2: The bioactive MK-7 form of Vitamin K2 is produced using bacteria like Bacillus subtilis natto, which ferments substrates such as soybeans in bioreactors.
Sustainability Differences: Microbial fermentation is generally a more sustainable and environmentally friendly process than chemical synthesis, which relies on petrochemicals and toxic solvents.
Purity and Isomers: Synthetic vitamin K often contains a mix of isomers, whereas fermented MK-7 is naturally produced in the more bioactive all-trans form.
Technological Advancements: Modern manufacturing employs innovations like genetically engineered microorganisms and biofilm reactors to increase yields and improve efficiency.

Vitamin K, an essential fat-soluble vitamin, plays a critical role in blood coagulation and bone health. It exists in several forms, primarily phylloquinone (K1), found in plants, and menaquinones (K2), synthesized by bacteria. Due to its importance, industrial-scale production is necessary for supplements and functional foods. The manufacturing process for vitamin K varies significantly depending on the specific form being produced, but typically involves either chemical synthesis, microbial fermentation, or natural extraction.

Chemical Synthesis of Vitamin K1 (Phylloquinone)

Chemical synthesis is a long-established method for producing Vitamin K1 and relies on multi-step reactions using precursor compounds. While effective, it has notable limitations, including low yields, unwanted byproducts, and the use of harsh chemicals.

The process generally follows these stages:

Selection of Precursors: The process begins with basic chemical compounds, most commonly menadione (Vitamin K3), which is itself a synthetic vitamin K compound. Menadione is synthesized from 2-methylnaphthalene via oxidation.
Condensation: To form the more complex structure of Vitamin K1, the menadione is first reduced to menadiol. This menadiol monoester is then condensed with isophytol in the presence of a catalyst, such as boron trifluoride etherate.
Saponification: Protective groups added during the condensation phase are removed using a strong base, which breaks the protective bonds.
Oxidation: The resulting product is oxidized using a catalyst, like silver oxide or air, to form the final Vitamin K1 structure.
Purification: The final product is purified, often through crystallization, to remove impurities and unwanted isomers.

Chemical synthesis has been criticized for its environmental impact, leading many manufacturers toward more sustainable alternatives.

Microbial Fermentation for Vitamin K2 (Menaquinones)

Microbial fermentation is the primary method for producing natural Vitamin K2, particularly the highly bioavailable menaquinone-7 (MK-7). This process is considered more sustainable and is preferred by consumers seeking natural source supplements. The process leverages microorganisms, most notably Bacillus subtilis natto, to produce the vitamin.

The fermentation process involves several key steps:

Strain Selection: The microorganism, often a strain of Bacillus subtilis natto, is carefully selected for its high MK-7 production yield. Genetic engineering can further enhance the productivity of these strains.
Fermentation: The bacteria are grown in bioreactors containing a nutrient-rich substrate. Traditionally, this is done using solid-state fermentation (SSF) on materials like soybeans, mirroring the production of traditional Japanese natto. Liquid-state fermentation (LSF) and advanced biofilm reactors are also used for large-scale production.
Extraction and Purification: After the fermentation period, the MK-7 is extracted from the fermented medium or bacterial cells using organic solvents like n-hexane. This is followed by purification steps, such as chromatography and crystallization, to achieve a high-purity product.

Natural Extraction Methods

Natural extraction is an alternative for obtaining phylloquinone (Vitamin K1) from plant sources such as green leafy vegetables. However, this method faces significant limitations on an industrial scale.

Steps for natural extraction:

Sourcing Raw Materials: Large quantities of vegetables like spinach or kale are required.
Extraction: The vitamin is extracted from the plant material using complex solvent-based processes.
Purification: Multiple purification steps are needed to isolate the vitamin from the plant matrix, which results in a low overall yield and is often not commercially viable for large-scale production.

Comparing Manufacturing Methods: Chemical vs. Fermentation


Aspect	Chemical Synthesis	Microbial Fermentation
Sustainability	Lower; relies on petrochemicals and uses harsh, toxic solvents and catalysts.	Higher; utilizes renewable feedstocks and avoids many harsh chemicals.
Cost-Effectiveness	Generally more cost-effective for large-scale K1 production due to scalability.	Can be more costly due to batch production and complex downstream processing, though advancements are reducing costs.
Purity	High purity is achievable but often contains a mix of isomers, including the less-bioactive cis forms.	High purity, with a focus on the bioactive all-trans isomer, is a key advantage.
Supply Chain	Offers strong supply chain security and consistency due to standardized synthetic reactions.	Can face supply chain variability linked to biological processes, though engineering mitigates this.
End Product	Creates Vitamin K1 (phylloquinone) or synthetic K3, which can be further processed.	Primarily produces natural Vitamin K2 (menaquinones), especially MK-7.

The Future of Vitamin K Production

As demand for high-quality, naturally-sourced nutraceuticals grows, microbial fermentation is poised for continued growth and innovation. The future of vitamin K production is likely to focus on several key areas:

Biofilm Reactors: Advancements like biofilm reactors, which use microbial colonies on composite supports, can significantly increase vitamin K yield and efficiency.
Metabolic Engineering: Using advanced genetic tools like CRISPR-Cas9 allows scientists to engineer microorganisms to be more efficient vitamin K producers, increasing yield and quality.
Sustainability Improvements: As research evolves, methods will continue to be refined to enhance sustainability and lower environmental impact across all production methods, including optimizing chemical processes and reducing solvent use.

Conclusion

In summary, the manufacturing of vitamin K is a tale of two different approaches: the long-standing, often less sustainable chemical synthesis for Vitamin K1, and the more modern, environmentally friendly microbial fermentation for Vitamin K2. While chemical synthesis offers consistency and scalability, fermentation is gaining ground due to consumer demand for natural products and its improved sustainability profile. Ongoing research in genetic engineering and bioprocessing is continuously improving the efficiency of microbial fermentation, paving the way for more natural, high-quality vitamin K supplements.

An Improved and Plant Viable Synthesis of Vitamin K1

Frequently Asked Questions

Naturally sourced vitamin K, typically K2 from fermentation, comes from microorganisms like bacteria. Chemically synthesized vitamin K, primarily K1, is produced through laboratory chemical reactions using synthetic precursors.

The most common microorganism used for industrial production of vitamin K2 (MK-7) is Bacillus subtilis natto, which is also used to make the fermented Japanese food, natto.

Microbial fermentation is more sustainable because it uses renewable feedstock and avoids many of the toxic solvents, heavy metals, and harsh acids associated with traditional chemical synthesis methods.

Yes, chemically synthesized vitamin K1 can have a lower yield, may contain less-effective cis isomers, and its production process involves toxic chemicals and generates more environmental waste compared to fermentation.

After production, whether by fermentation or synthesis, the vitamin K undergoes rigorous purification processes, which may include chromatography and crystallization, to remove impurities and ensure the final product is highly pure.

Genetic engineering techniques, such as CRISPR, are used to modify microorganisms like Bacillus subtilis to increase their vitamin K production efficiency and yield, making the fermentation process more productive.

Yes, fermented vitamin K2 (MK-7) primarily consists of the all-trans isomer, which is significantly more bioactive than the cis isomers often found in chemically synthesized products.