Vitamin

K2

Best L a t e s t n e w s a b o u t V I TA M I N M K 7
Practices
Handbook

1
KNOW THE
VITAMIN MK7
REAL COMPOSITION

2
KNOW THE NATURAL
ORIGIN OF VITAMIN MK7
FROM B. SUBTILIS NATTO

3
The Key KNOW THE STABILITY PROFILE
OF MK7 TO SHORT-LIGHT

Points for EXPOSURE AND FORMULATIONS

Optimal 4
MK7 KNOW THE VITAMIN MK7
COMPLIANCE WITH
THE QUALITY STANDARDS

5
KNOW THE VITAMIN MK7
RELIABLE SUPPLY CHAIN
 KNOW THE VITAMIN MK7
REAL COMPOSITION
1
KEY POINT
VitaMK7
the excellence
in all-trans
MK7 quantity
The biological activity of menaquino-
ne-7 is strictly linked to its natural,
structural all-trans configuration.
Cis-analogs of vitamin K2 are biologi-
cal inactive.
In natural environments, bacteria produ-
ce menaquinone-7 only in the trans form
whereas the synthetic methods produce
a mixture of both trans and cis isomers by
default, with potential presence of
different impurities.
O the very high purity assay of the mena-
CH3
O
H
O
Active all-trans MK7
CH3
O H
Inactive cis MK7
Synthetic production involves aggressive
purification processes to separate the
biological active form.
KNOW THE NATURAL ORIGIN OF
VITAMIN MK7 FROM B. SUBTILIS NATTO
VitaMK7 is the only natural-derived from Bacillus subtilis natto
"Get back to nature and hear its lessons is
the first requirement here at Gnosis to
develop and produce the right vitamin
MK7.
Following this insight an innovative
industrialization method based on the
fermentation of Bacillus subtilis subsp.
natto has been developed and optimized
to deliver natural, high pure (>99%)
vitamin K2 as MK7, under the brand name
of vitaMK7.
Used for hundreds of years by the
Japanese people, Bacillus subtilis natto
is the only subspecies of Bacillus family
that has been used to produce Japane-
se natto food, recognized to contribute
to a healthy gut flora and vitamin K2
intake.
The history of the use of Bacillus subtilis
natto has demonstrated the efficacy and
KNOW THE STABILITY PROFILE
3
KEY POINT
OF MK7 TO SHORT-LIGHT
EXPOSURE AND FORMULATIONS
Chemical solvents must be applied to
extract the trans isomer and eliminate
tion process allows to respect and preser-
ve the natural all-trans structure of the VitaMK7 is suitable in formulation with different Calcium salts without
the unnatural and inactive cis forms and menaquinone-7, avoiding the possible
other impurities. Currently the synthe- (photo)-oxidative modifications of the applying any coating that increases non-natural chemical substances
tic-derived menaquinone-7 offers a side chain.
lower assay of all-trans isomer. The result is a product that has >99%
The topic of menaquinone-7 stability nate and calcium citrate, respectively. bad smell and the tendency to pack
of all-trans menaquinone-7, higher
Specification of than what is chemically possible, is recently booming on the health VitaMK7 is stable in several formula- typical of some other qualities of
100%
through the best chemical purification products market with conflicting tions included in liquid (water, yogurt, vitamin K2.
99%
99% techniques. published data that have puzzled oil) and milk powder preparations and
Concentration of MK7 (%)
98%
97% manufacturers of dietary supplements can boast an excellent recovery to short What is emerging from the reported
96%
95%
96% Isomeric purity Identification of by HPLC analysis and end-users, in an ever growing time light exposure, the real stability shortfall in the stability of different
94% 80 market where different sources and issue, of approximately 93%. occurring forms of vitamin K2 on the
Retention Time
93%
qualities of menaquinone-7 coexist.
23.353
92%
91%
60
90%
Gnosis consistently performs stabi- VitaMK7 has 3 years of stability at room temperature
Volts
0
vitaMK7 K2 Crystals & Synthetic
40
lity tests on its raw materials and The results of trials conducted have proven VitaMK7 has a recovery rate
20 tests potential harsh environment of MK7
The natural-derived vitamin MK7 merges
to support their applications in 99% with Calcium Carbonate
0
quinone-7 with the highest all-trans finished products, and vitaMK7 is 94% with Calcium Citrate
10 15 20 25 30 35 40
isomeric purity guaranteeing the highest Minutes not an exception. Stable in liquid (water, yogurt, oil) and milk powder
incomparable quality of the raw material. VitaMK7 shows also excellent recovery to short time light exposure
Only advanced chemical analysis such as Calcium formulations seem to be a (approx. 93%)
The naturally based production process Mass Spectroscopy (MS), Nuclear Magne- potential issue that has created a
of vitaMK7 guarantees the highest tic Spectroscopy (NMR) and Advanced palpable concern among the vast
content of all-trans MK7; it is the same HPLC method can establish the real majority of manufacturers of dietary The natto natural-derived vitaMK7 market - natural fermented K2 versus
natural process of fermentation with content of all-trans menaquinone, as supplements, who want to be sure results to be consistent, sustainable synthetic derived, with or without
Bacillus subtilis to avoid any other deeply demonstrated for Gnosis about the real content of vitamin K2. and free from environmental conta- calcium formulations - is that indepen-
isomers. Moreover, the gentle purifica- vitaMK7. Therefore a deep evaluation of the minants, suitable to be used stand dent third party laboratory results, in
behavior of vitaMK7 with the most alone or in formulations with place of reliable reference for vitamin
common calcium salts has been various calcium salts, without K2 players, are missing.
carried out, also in stress conditions. applying coating or microencapsu- In view of all this, Gnosis has started
lation that increase non-natural another independent study at a third
VitaMK7 shows excellent stability data, chemical substances. laboratory of analysis to unquestio-
3 years at room temperature and a nably certify the stability profile of
recovery rate of MK7 equal to 99% and VitaMK7 is a white, odorless, taste- vitaMK7 and to definitely assess its
94% in formulations with calcium carbo- less and fluent powder without the optimal quality profile.
Vitamin MK7 Vitamin MK7 2000ppm
2000ppm as is with CaCO3 & Calcium Citrate
2
KEY POINT - stability data in stress condition (40C) - - stability data in stress condition (40C) -
safety of the strain. No other Bacillus 100%
Synthetic
Commercial
1
species, such as licheniformis used in other microencapsulated 0,9
90%
K2 derivative, can claim the same profile of
Recovery % 21 days at 40C
0,8 Synthetic
Commercial Synthetic
Recovery % 21 days at 40C
safety and efficacy. Natural origin is 80% microencapsulated Commercial
From
Licheniformis 0,7 microencapsulated
preserved with natural extraction process. 70% 0,6
60% 0,5 99% 98% 94% 94%
Gnosis patented production method 50% 99% 97% 79% 0,4
resembles what occurs in the Japanese 40% 0,3
natto food production, merging history, 30% 0,2
science and technology.
20% 0,1
The identity of proprietary Gnosis non-GMO 10% 0
0 CaCO3 Ca Citrate
strain, isolated starting from a commercial 0
natto and deposited in the DSMZ
Collection, has been genetically characte-
rized by the most advanced techniques
confirming EFSA QPS (Quality Presump-
Recovery %
tion of Safety) requirements supporting
Vitamin MK7 2000ppm Natural vitamin k2 as MK7 48h 93%
safety.
The resulting product is consistent, stable, - Short time light exposure stability 48H - Synthetic Recovery %
sustainable, and free from environmental Commercial
contaminants. microencapsulated 48h 53%
 4
KEY POINT
KNOW THE VITAMIN MK7
COMPLIANCE WITH THE
QUALITY STANDARDS
VitaMK7 is the only one to meet the USP and TGA standard requirements
The use of the word standard close to totally natural-derived (no synthetic On the same topic, in August 2015 the
quality is often misused or abused, without production) vitamin K2 made up of Australian Health Authority - TGA (Thera-
the term really referring to acknowledged Bacillus subtilis natto (no B. licheniformis peutic Goods Administration) published a
definition. A standard of quality is a fermentation derived product) extract of note recognizing that the USP menaqui-
document of recognized excellence menaquinone-7. none-7 provides the guidance of the
established by an authority that provides quality expected for vitamin K2 products.
requirements and characteristics to ensure The US Pharmacopeial Convention issued
that products are fit for their purpose. three specific Monographs: VitaMK7 not only meets the require-
1. Menaquinone-7 ments but its profile solely contributed
The common definition of purity, metho- 2. Bacillus subtilis subsp. subtilis to the preparation of the above mono-
dology and requirements to define high Menaquinone extract graphs, getting the greater validation
quality standards for an ideal vitamin K2 3. Menaquinone-7 Preparation to become the USP Standard Reference.
ingredient is effective from August 1st, Gnosis exclusively contributed to the
2015, when the first Official Compendia This is a real milestone because an establi- drawing up of monographs working
Monograph of Dietary Supplement for shed USP monograph has become a closely with different teams at USP and
Vitamin K2 has been published in USP unified reference for the industry to accura- is already supplying USP with the
38-NF33 First Supplement. It refers to a tely identify vitamin K2 as MK7. vitamin K2 Standard Reference.

KNOW THE VITAMIN MK7

5
KEY POINT

RELIABLE SUPPLY CHAIN

VitaMK7 is produced in a GMP Manufacturing Site located in Pisticci (Italy)
VitaMK7 is produced by Gnosis proprietary
patented biofermentation process of Bacillus Gnosis biofermentation
subtilis spp natto (EP 1803820; US 7,718,407; process of
JP 5043425) in its own cGMP manufacturing Bacillus subtilis
site located in Pisticci, Italy. spp natto
cultures

Packaging

The entire supply chain of vitaMK7, from the The very high grade of quality chain and the
raw material to the finished large range of proven reliability are offered by Gnosis from
Gnosis is the straight and direct manu- vitaMK7 powder/oil grades, is controlled and production to services, from preparation to
facturer with no intermediaries or carried out in compliance with the rules of processing, from storage to logistics, from
brokers, a warrant of origin, quality and Gnosis' Quality Management System QMS's, transport to distribution, from administra-
safety of all products under vitaMK7 ISO and HACCP quality systems. Kosher and tion to sale management.
umbrella. Halal certificates are also available. The Pisticci Operations is also FDA approved.

References:
Knauer et al. J Nutr. 1975. - Sato et al. J Biosci Bioeng. 2001. - Sanders et al. Compr Rev Food Sci Food Safety 2003. - Ikeda et al. J Nutr. 2006. - Brug et al. Brit. J. Nutr., 2011.
Gigante et al. J Tissue Eng Regen Med 2015 - http://www.usp.org/sites/default/files/usp_pdf/EN/dietarySupp/2015-dsc-vol-1-table-of-contents-ref-standard-index.pdf.

This product is not intended to diagnose, treat, cure or prevent any disease. These statements have not been evaluated by the Food and Drug Administration.

Gnosis S.p.A Gnosis USA Inc.

Via Lavoratori Autobianchi, 1 4259 West Swamp Road, 3rd Floor Suite 305
20832 Desio (MB) Italy Doylestown, Pennsylvania 18902 - USA