vitaMK7® : Natural Fermentation Process

Gnosis by Lesaffre has been a pioneer in the development of vitamin K2 as Menaquinone-7 (MK-7): our first production was launched almost 20 years ago! From the origin, our research has been focused on a unique natural microbial source of K2: the bacteria Bacillus subtilis natto. vitaMK7® is therefore based on a proprietary microbial strain of these bacteria, deposited in DSMZ collection under the accession number DSM 17766.

Gnosis by Lesaffre production relies on an industrial patented fermentation process, which enables to maintain the naturalness and the indistinguishable potency of MK-7. vitaMK7® is totally NATURAL and its production process does not use any chemicals.

Gnosis by Lesaffre patented production process allows:

  • MK-7 with a purity of all trans isomer higher than 99%
  • Preservation of the original biological structure of the active molecule
  • Avoiding (photo)-oxidative modifications maintaining the all-trans structure of the side chain
Gnosis by Lesaffre patented production process allows:

vitaMK7® : High Level of Purity

The biological activity of MK-7 is strictly linked to its natural, structural all trans configuration. In natural environments, bacteria produce menaquinone-7 only in the trans-form. vitaMK7® is a natural vitamin K2 as MK-7 with a very high level of purity: it contains >99% of all trans. Menaquinone7 (MK-7), the only active form of vitamin K2.

vitaMK7® purity means:

  • No contamination from fermentation process
  • No bacterial residues
  • No need for calcium addition and crystals
  • No need for synthetic or other form

The purity of vitamin K2 is dual. It is measured by:

  1. The isomeric purity, i.e. the percentage of trans isomer (the active form of vitamin K2 as MK-7) in the product vs. cis isomer (inactive);
  2. The general purity, i.e. the percentage of substances which are actually vitamin K2 within the product vs. other substances resulting from the manufacturing process.

These “general” impurities are therefore different for natural vitamin K2 from fermentation vs. synthetic vitamin K2.
Gnosis used the most advanced detection techniques (HPLC) to identify the (all-trans) configuration.

vitaMK7® : High Level of Purity

vitaMK7® is also the stable natural vitamin K2 as MK-7:

  • vitaMK7® active ingredient has 3 years of stability at room temperature
  • vitaMK7® in formulation offers at least 2 years of stability at room temperature

vitaMK7® shows excellent recovery to a short time light exposure (rate of loss in assay for a 2000ppm in maltodextrin of approx. 0.12% for every hour of exposure at a light intensity of 750 lux).

vitaMK7® : Clean Label and Transparency

“Clean label” refers to key attributes which are globally recognised and linked with transparency, wholesomeness of the ingredients and the lack of artificial/added components and allergens.

At the heart of the clean label is the demand to use ingredients with real nutritional benefits that are as close to their natural state as possible, like ingredients from natural sources, and to avoid highly processed ingredients, such as those from genetically modified organism or chemical synthesis.

Gluten free, Lactose free, Toxins & pesticides free, Soy free, non-GMO, Animal material free: these attributes demonstrate that vitaMK7® is a clean vitamin K2 as MK-7.

vitaMK7® is also suitable for vegetarians:

  • vitaMK7® does not contain any animal material
  • vitaMK7® is KOF-K certificated
vitaMK7<sup>®</sup> is also suitable for vegetarians:

vitaMK7® : Relying on european manufacturing

Gnosis by Lesaffre is the sole European producer of Vitamin K2 as MK-7, where the entire supply chain, from the raw material to the finished product (both powder & oil, whatever the grade), is without intermediates or brokers. The production process is carried out in our own approved cGMP plants located in Pisticci (Italy) and Sant’Antonino (Switzerland) in compliance with the strictest quality rules, ISO and HACCP quality systems. Both sites are FSSC 22000 certified.
A brand-new, integrated manufacturing site, successfully inspected by the FDA, encompassing a multipurpose plant for fermentation-derived products.

  • Modular structure which supports different process flow models.
  • Fully automated plant for management of manufacturing activities in remote mode.
  • Truly and Certified European origin

Moreover, we implemented a thorough Quality Management System which enables complete transparency and we offer our customers and partners the possibility to visit the 133.000 m² plant and control every step of the vitaMK7® manufacturing process.

vitaMK7® : Relying on european manufacturing

vitaMK7® : Benefits clinically proven

Pre- and clinical studies published in peer-reviewed journals have demonstrated the efficacy and innocuity of vitaMK7®, and its benefits to human health.

Effect of MK-7 on PGE-2 synthesis in bone forming osteoblasts

Co-incubation with vitaMK7® inhibits the PGE-2 release induced by TNFalpha. vitaMK7® is effective in inhibits PGE-2 production to levels comparable to baseline values.

Preclinical studies (in vitro)
vitaMK7® was tested in a cell culture of bone forming osteoblasts. Cells were activated with TNFalpha, a pro-inflammatory cytokine. The treatment with TNFalpha induces a high release of PGE-2 prostaglandins, a mediator of inflammation. After activation the secreted PGE-2 levels were measured.

Synergic effect of vitaMK7® and vitamin D3-induced osteogenesis.

The association of MK-7 to vitamin D3 has important osteo-inductive effects in relation to bone matrix mineralisation through induction of osteocalcin synthesis and carboxylation. The study shows a synergic effect of the association MK-7/D3 with a rise of cOC in treated cells.

Preclinical studies (in vitro)
vitaMK7® and vitamin D3 have been tested separately and in combination in cultured human osteoblasts in vitro.

vitaMK7® bioavailability in single dose oral administration in healthy volunteers

MK-7 plasmatic levels raised significantly following the administration of vitaMK7®. The long half-life of MK-7 contained in vitaMK7® in blood is confirmed by the plasmatic levels measured at 24 h. These values are comparable with those reported in literature (Schurgers et al., Blood 2007) for a menaquinone-7 single oral administration.

Clinical-studies
AUC values following a single oral dose administration of vitaMK7® in healthy volunteers

Gnosis’ clinical trials

Supplementation with MK-7 enriched olive oil resulted in a significant and dose-dependent increase in plasma levels. The high dose significantly increased cOC and decreased uOC plasma levels, resulting in a significant increase in the cOC:ucOC ratio, a well-recognised index of the functionality of osteocalcin.

Clinical-studies
Ref: F. Brugé, T. Bacchetti, F. Principi, G.P. Littarru and L. Tiano. Olive oil supplemented with Menaquinone-7 significantly affects osteocalcin carboxylation. British Journal of Nutrition 2011, 1-5

  • Bacterial mutation in S.typhimurium and E.Coli

vitaMK7® does not induce reverse mutation in S.typhimurium and E.Coli at doses up to 5,000 µg/ml.

  • Mutation in L5178YTK +/- mouse lymphoma cell

The test concluded that vitaMK7® does not induce mutation at concentrations up to 1,000 µg/ml.

  • Chromosome aberrations in Chinese hamster ovary cells (CHO) in vitro

No chromosomal aberrations were observed in CHO after in vitro treatment with concentrations of vitaMK7® up to 125 µg/ml.

  • Single dose oral toxicity

The lack of mortality points out that the maximum tolerated dose is greater than 2,000 mg/kg body weight, a dose about 20 times the one suggested for human use.

  • 28 days repeated dose toxicity in rats

The No Observed Adverse Effect Level (NOAEL) in this study is considered to be 100 mg/kg/day, which is the highest dose level investigated.