Vitamin K2 MK-7: A stability challenge, a market study

30-Apr-2017 Last updated on 27-Jun-2019 at 07:43 GMT

Demand for vitamin K2 has increased rapidly over the past decade as awareness of its
role in bone and cardiovascular health has spread. However, studies run by Kappa
Bioscience show many K2 products contain lower-than-claimed levels of the vitamin, a
finding that threatens to undermine the market and its products’ ability to provide health
benefits and slow the natural effects of aging.

Interest in K2 stems from its role in regulating calcium. K2 activates osteocalcin proteins
which incorporate calcium into bone. Bone mass acquired through childhood and
adolescence leads to healthy bones later in life, which are needed to sustain physical
stress and avoid diseases including osteoporosis and osteopenia. Bone mass declines
throughout adult life, with peak bone mass (PBM) achieved in childhood at the age of 13 to
19 years [1]. A 10% increase in PBM is estimated to reduce the risk of osteoporotic
fracture as we age by 50% [2].

Vitamin K2 also activates matrix GLA (MGP) protein which binds excess calcium to
prevent deposit in soft tissues such as arteries, a significant risk factor in cardiovascular
disease [3] and a common condition as we age. Vitamin K2 is deficient in the western diet
[4], and, as such, supplementation is critical to good health. The MK-7 form of K2 is
optimal for dietary supplementation because it has a half-life of two to three days,
compared to the one to two hours of MK-4 [5, 6].

A fundamental property of K2 is also the root of the market’s problems, though.

Is K2 stability really a problem?

In 1948, the Federal Security Agency identified the degradation of the fat-soluble vitamin D
in certain formulations and environments [7]. The agency found products combining D and
calcium were “almost invariably ... low in vitamin D within a month or two of the time of
manufacture.” Producers of vitamin D products have since acted to extend shelf life.

These decades-old findings suggest other fat-soluble vitamins, such as K2, may also
degrade when formulated with calcium or magnesium. However, the potential for K2 to
degrade was little discussed or investigated in the early years of the growth of the market.

If K2 degrades in the presence of calcium and magnesium, it would prove problematic

because the minerals are central to many bone and heart health product formulations, as
well as products aimed at the multivitamin, women's health and healthy-aging markets.
Such degradation would limit the use of K2 in these categories to K2-alone or K2 plus non-
mineral formulations.
Until recently, the idea that K2 degrades in certain formulations was backed up by little
more than speculation. That began to change in 2013, the year after Kappa Bioscience
launched the first K2 MK-7 produced by an organic synthesis. Prior to that, all K2 MK-7
was made using the traditional natural-fermented production process.

To compare the performance of synthesized versus fermented K2, Kappa tested 101
finished products for label claim. Fully 81% did not meet label claim, including products
that used Kappa’s K2.

Kappa set out to discover what was causing this previously-undiscovered K2 stability
issue. Investigations eventually centered upon a fundamental characteristic of vitamin K2.
As a fat-soluble vitamin, and similar to all fat-soluble vitamins such as A, D and E,
unprotected vitamin K2 degrades in certain environments and formulations.

In response to this discovery, Kappa invested in the development of a microencapsulated

MK-7 format to solve the K2-plus-minerals problem. That ingredient is now backed by 12
and 24-month stability testing data against unprotected natural-fermented K2. This allowed
Kappa to move into market categories where calcium or magnesium are used.

To continue its long-term scientific effort to identify, resolve and evaluate the K2 stability
issue, Kappa decided to revisit its earlier market study. In 2016 Kappa tested nearly 100
finished products for K2 label claim. Products were acquired from retailer shelves in
Europe and elsewhere.

The study answers two important questions: Is the K2-plus-minerals stability problem real?
Does K2 stability affect brands or consumers?

State of the market 2016: The science of stability

The design of the 2016 market study was based on earlier long-term K2 stability studies.
These prior studies showed that unprotected or natural-fermented K2 was unstable in
formulation with calcium at 25ºC and 40ºC. At those temperatures 60% and 29% of K2
remained after 12 months, respectively. The results for K2 combined with magnesium
were significantly worse. After 12 months only 1% of the unprotected K2 remained in
formulations containing magnesium.

In comparison, 96% of the protected, microencapsulated K2 with calcium was detected

after 12 months at 25ºC, and 86% was detected after storage at 40ºC. The results when
formulated with magnesium were similar, at 92% and 80%, respectively.

The 2016 market results were less than encouraging. A total of 96 finished products were
tested, primarily purchased from retailers in the EU, but also the US, India and South
Africa. A range of dosage formats were included. Products were tested for K2 MK-7
content compared against stated label claim by a leading analytical lab using a validated
HPLC method. After removing duplicate tests of single products, and removing seven
products that fell outside the study reporting criteria (for reasons other than label claim
results), the final study reported on 79 products.

Fully half of the 39 unprotected or natural-fermented K2 plus calcium or magnesium

products tested missed label claim by 50% or more. One-in-five-products contained less
than 10% of K2 label claim. Four products had no measurable K2. Only 8% of unprotected
K2-plus-minerals products met or were close to label claim. In comparison, all of the
protected, microencapsulated K2 MK-7 products met or were close to label claim.

Recent K2 market developments, including the entry of a wider range of global ingredient
manufacturers using natural-fermented production processes, prompted Kappa to expand
the scope of the 2016 study.

To investigate general K2 quality, stability and performance, Kappa expanded the study to
include a sample of K2-alone and K2 in non-mineral formulation products. All used
unprotected, natural-fermented K2 MK-7 in formulations where stability should not be an
issue. A total of 30 products were tested for label claim.

About a quarter of these products performed very well, with four meeting label claim, and
another four demonstrating 95% to 99% of K2 label claim. These results would be
expected for K2 MK-7 products that do not contain minerals.

However, half of the K2 non-mineral products performed very poorly. Fully one-third of the
sample had zero measurable K2 content. The remaining ‘poor performers’ registered K2 in
the 26% to 75% of label claim range. Another seven products missed K2 label claim by
10% to 20%.
A second look at unexplained results

The results for the unprotected K2-alone or K2 plus non-mineral products were
unexpected and no ready explanation was apparent. A closer look, however, provided a
clue. These 30 products were sorted and analyzed according to the country where the K2
MK-7 ingredient was manufactured, not where the finished product was made. Of the 30
products, 25 shared a common K2 origin from a specific region of the world.

Of these 25 products, a quarter performed well, demonstrating 95% to 100% of K2 label

claim. Another quarter performed at a less-than-ideal 80% to 94% of K2 label claim. The
remaining half of these products performed poorly, with 40% demonstrating no
measurable K2 content.

While half of this geographical subset performed in the range of 80% to 100% of label
claim, only 24% met or were close to label claim in formulations that should not pose
stability challenges to K2 MK-7.

Conclusions

Vitamin K2 MK-7 is a fat-soluble vitamin. Like all fat-soluble vitamins, it can degrade in
certain environments and formulations. K2 is particularly susceptible to degradation in
formulation with calcium or magnesium. Unprotected vitamin K2 combined with calcium or
magnesium will degrade, with significant risk that products will not meet the stated label
claim — and likely by a wide margin. Kappa’s 2016 market study supports this conclusion,
or at minimum raises a call for more study and industry attention to this issue.

Calcium is a central ingredient in bone health formulations, and magnesium is a frequent

co-ingredient in heart health formulations. Without a solution to the unprotected K2-plus-
minerals stability problem, the use of vitamin K2 MK-7 is restricted in these and other
market categories that often use minerals, including the multivitamin, women’s health and
health-aging categories.

The key that opens the door to these markets is a protected vitamin K2 MK-7, which
ensures product stability through microencapsulation or an innovative dosage
format. Alternatively, the key may lie in the science of unprotected K2-plus-minerals
degradation such that the rate of MK-7 decay can be offset by overage in manufacturing.

Regardless of the solution, consumers and brands alike should have confidence that their
product is delivering on the promise of this essential vitamin.

References

1. Bailey, D.A., R.A. Faulkner, and H.A. McKay, Growth, physical activity, and bone
mineral acquisition. Exerc Sport Sci Rev, 1996. 24: p. 233-66.

2. Bailey, D.A., The Saskatchewan Pediatric Bone Mineral Accrual Study: bone mineral
acquisition during the growing years. Int J Sports Med, 1997. 18 Suppl 3: p. S191-4.

3. Schurgers, L.J., J. Uitto, and C.P. Reutelingsperger, Vitamin K-dependent carboxylation

of matrix Gla-protein: a crucial switch to control ectopic mineralization. Trends Mol Med,
2013. 19(4): p. 217-26.

4. Cundiff, D.K. and P.S. Agutter, Cardiovascular Disease Death Before Age 65 in 168
Countries Correlated Statistically with Biometrics, Socioeconomic Status, Tobacco,
Gender, Exercise, Macro- nutrients, and Vitamin K. Cureus, 2016. 8(8): p. E748.

5. Moller, M., et al., Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs

Fermentation-Derived MK-7 in Randomised Controlled Trials. Int J Vitam Nutr Res, 2016:
p. 1-15.

6. Schurgers, L.J., et al., Vitamin K-containing dietary supplements: comparison of

synthetic vitamin K1 and natto-derived menaquinone-7. Blood, 2007. 109(8): p. 3279-83.

7. Nelson, E. M., DETERIORATION OF VITAMIN D WHEN MIXED WITH CALCIUM

SALTS. JAMA, 1959. 171: p. 1103.

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editorial team. For more information on this article, please contact Kappa Bioscience.