VitaMK7, the Gnosis by Lesaffre vitamin K2 as MK7 in a qualified supply chain

Gnosis by Lesaffre is the sole European producer of Vitamin K2 as MK7, where the entire supply chain, from the raw material to the finished large range of vitaMK7 powder/oil grades, is without intermediates or brokers. The production process is carried out in it is own approved cGMP plant in compliance with the strictest quality rules, ISO and HACCP quality systems. Moreover, a Gnosis’ Quality Management System is in force in the manufacturing plant.

Supply chain visibility and transparency are a priority in the manufacturing of vitamin K2 as MK7, due to the different origin of raw materials present in the market (fermentation-derived or synthetic-derived) and the presence of several players that claim they produce the ingredient, but cannot provide information about the manufacturing plants of their production.

Moreover, the MK7 market is extremely appealing for new players, with a global market that is expected to grow with a CAGR of roughly 24.7% over the next five years and will reach $270m in 2024, from $73m in 2019, according to a new GIR (Global Info Research) study, but with potential poor reliability and quality of new producers/suppliers.

Gnosis by Lesaffre boasts more than 10 years' experience in producing vitamin K2, applying biofermentation manufacturing process to highly purified natural microbial strain, the Bacillus subtilis natto, under strictly controlled conditions. Nowadays, the company is leader in the production and commercialisation of this ingredient under the brand name of vitaMK7.

The entire supply chain is constantly monitored, and the structured quality system allows the company to work in complete transparency

Since many years, Gnosis by Lesaffre has focused its effort in the manufacturing of high-quality vitamin K2 as MK7, investing first in R&D and technological development of the ingredient, and subsequently in the quality of the production process, industrial activities that allowed the company to obtain a granted patent process of production of its vitamin K2 ((EP 1803820; US 7.718.407; JP 5043425).

Moreover, the company has immediately recognised the value and advantages of increasing supply chain transparency of vitamin K2, sharing certain information with clients, partners and consumers to build trust and solid business relationships.

Gnosis by Lesaffre is the sole European producer of Vitamin K2 as MK7, where the entire supply chain, from the raw material to the finished large range of vitaMK7 powder/oil grades, is without intermediates or brokers. The production process is carried out in it is own approved cGMP plant in compliance with the strictest quality rules, ISO and HACCP quality systems. Moreover, a Gnosis’ Quality Management System is in force in the manufacturing plant.

The entire supply chain is constantly monitored, and the structured quality system allows the company to work in complete transparency, offering customers and partners the possibility to visit the 133.000 square meters plant and control every phase of the vitaMK7 manufacturing process. Recently the plant was equipped with a 120 m3 fermentation line entirely dedicated to the production of vitaMK7.

The high quality of the ingredient, the safety and the stability claimed are the result of the deep know-how acquired by the company over the long term and currently applied according to European quality standards on its own factory. VitaMK7 has also KOSHER certifications.

VitaMK7 also offers "Clean label", a recognisable value by the global market. The raw material, really, deriving from the biofermentation of a highly purified natural microbial strain of Bacillus subtilis natto, grown under strictly controlled conditions, follows what happens in the natural environment during the production of the Japanese natto food.

Vitamin K2 as MK7, in fact, was isolated for the first time in this traditional fermented soybean food. Natto is produced via the natural fermentation of boiled soybeans through the action of a specific bacteria, the Bacillus subtilis spp. natto. Today in Japan Bacillus subtilis spp. natto is considered as the sole bacterium needed to produce good natto. One hundred grams of natto contains approximately 1,000 μg of MK7. Bacillus subtilis natto produces MK7 only in the trans form.

In humans, the trans isomer of MK7 is essentially responsible for the vitamin’s biological activity and plays a crucial role in bone and cardiovascular health

Since the strains of Bacillus subtilis natto used for manufacturing natto food is edible, the fermentation-derived production method offers benefits because it provides a reproducible source of MK7, resembling the characteristics and chemical profile of MK7 - including the all-trans form - found in naturally-enriched K2 foods. Furthermore, all the clinical trial data and outcomes published were performed with fermented vitamin K2 as MK7.

The importance of all-trans structure of menaquinone

All-trans structure is peculiar to all menaquinones - produced by bacteria in natural environments - and allows them to play a key role in prokaryotic respiratory electron transport chains by functioning as electron carriers in the cytoplasmic membrane. In addition to a role in microbial respiration, MK forms exhibit antioxidant properties and can play a role in protecting cellular membranes from lipid oxidation.

In humans, the trans isomer of MK7 is essentially responsible for the vitamin’s biological activity and plays a crucial role in bone and cardiovascular health. Cis-analogs are considered biologically inactive (78).

Among the different raw materials derived from the same source, it is the quality of the production method that makes the difference. State-of-the-art biotechnology and expertise of fermentation-derived production processes can critically affect the quality profile of the MK7 ingredient and the all-trans content. In fact, analysis of MK7 finished products present in the market reveals that their isomeric purity is variable and can influence biological responses. Moreover, very recently, synthetic methods have been proposed for small scale production but the fermentation-derived process is arguably superior in terms of assay of final product, all-trans assay and purity profile. Usually, the synthetic methods produce a mixture of both trans and cis-isomers by default and chemical solvents are used to extract the trans isomer and drive away the cis-isomers and the other impurities. Only the analysis of isomeric purity can unveil the identity and the real content of the menaquinone-7 isomer, discriminating and quantifying the other cis-isomers and regioisomers.

It is considered as a reusable technology because compounds are easily degradable, the process requires less energy and creates less waste during production

The all-trans isomeric purity is commonly determined by high performance liquid chromatography (HPLC), combining this technique with mass spectroscopy and nuclear magnetic spectroscopy methods, which can reveal not only the presence of cis analogs but also natural/unnatural impurities. HPLC is carried out using a chiral separation. However, chiral separations can be time consuming and typically involve the use of expensive chiral columns. These chemical analyses are valuable tools for natural product identification, as well as the authentication, distribution and quantification of constituents in biogenic raw materials and are currently used to test natural medicines and biological materials obtained from model organisms, animals and humans. For this reason, the industrial manufacturing of MK7 has historically been centered on the fermentation- derived process: it guarantees a final product as nature intended, with high reproducibility and good scalability. Bioprocesses take advantage of the same enzymatic pathways of bacteria to execute MK7 production. The process requires the optimization of production medium to maximise the metabolite yield by using a wide range of techniques respecting the natural biosynthetic route of Bacillus subtilis natto. Other key elements of fermentation-derived processes are the optimisation of downstream processing for extracting, concentrating and purifying the product from a diluted fermentation broth. Finally, the fermentation-derived process is based on renewable resources and yields a green, clean and sustainable product. It is considered as a reusable technology because compounds are easily degradable, the process requires less energy and creates less waste during production.

Applying science and know-how to vitamin K2 as MK7 production

Gnosis’ process comes from the well-controlled fermentation processes of a non-genetically modified strain of Bacillus subtilis natto, isolated from the commercial Japanese natto food. The strain has been deposited in the DSMZ Collection (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH), under the accession number DSM 17766.

VitaMK7 is free from all known allergens, metals and organic solvents and "Free From" claims can be applied. The manufacturing process does not include starch-containing plant powder like soya or rice flour and is stated as soy- and gluten-free. VitaMK7 is the only menaquinone-7 in compliance with USP Standard Reference, which defines purity, methodology and requirements of the high-quality standard for an optimal vitamin K2.

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Gnosis by Lesaffre (more information, website)