Bioequivalence – Natural vs. Synthetic K2
synthetic or fermented: same biological function
Vitamin K2 MK-7 is manufactured using one of two production processes: a chemical synthesis or a biochemical synthesis (fermentation process)
Currently, about 30% of K2 MK-7 ingredient production is based on synthesis and the remainder on a fermentation process. This will change. Synthesis production provides several advantages over fermentation production. Over 90% of vitamins on store shelves are produced via a synthesis process. Synthesis of a vitamin is the primary technological innovation which makes mass-market commercialization possible. With K2VITAL®, Kappa Bioscience was the first company to launch a K2 produced in a synthesis production process – about 70 years after Doisey’s Nobel-winning of vitamin K1. Synthetically produced vitamin K2 creates an identical molecule to that found in nature.
Fermentation-derived K2 products have been shown in clinical studies to prevent and reverse arterial calcification and improve bone mineral density in healthy postmenopausal women. Since K2VITAL® is a synthetic MK-7 form, two studies were performed to determine whether synthetically derived MK-7 is equally effective as fermentation-derived MK-7 at raising blood vitamin K2 levels and activity.
K2VITAL® and fermentation-derived MK-7 have the same bioavailability. In the first cross-over design trial, K2VITAL® and fermentationderived MK-7 were administered to 16 healthy volunteers as a single 180 μg dose to determine whether they are equally well absorbed and demonstrate similar detection levels in blood samples during the three days after consumption. Blood analysis of the two treatment groups throughout the study period indeed demonstrated that the two MK-7 forms are bioequivalent.
K2VITAL® and fermentation-derived MK- 7 demonstrated equal reduction of inactive osteocalcin (ucOC). In the second trial, a placebo, three K2VITAL® doses (45, 90 or 180 μg) and one dose (90 μg) of natural-fermented MK-7 were given daily to healthy adults over a period of 43 days. To investigate MK-7 activity, researchers measured how much of the uncarboxylated osteocalcin (ucOC) was transformed into the carboxylated form (cOC) after activation by MK-7. As expected from known K2 activity, blood concentrations of ucOC decreased at the end of the study, when compared to study start, while cOC levels increased. The cOC increase at the end of the study was equal for both daily supplementation of 90 μg synthetic and natural K2. An equal increase of MK-7 in blood by supplementation of K2VITAL® and fermentation-derived MK-7 was observed.
Synthesis creates a pure, all-trans menaquinone-7 molecule
- Ingredient purity is enhanced significantly by synthesis production compared to fermentation. Synthesis creates a pure, all-trans molecule that is free of the impurities typically present with fermentation produced MK-7.
- Synthesis improves product aesthetics as fermented K2 can take the form of a brownish powder that retains an odor. A synthesized production process guarantees an allergen-free ingredient.
- Finally, the pure crystalline form of synthesized K2 production supports secondary manufacturing processes such as the microencapsulation of the MK-7 molecule to promote ingredient stability.
- The commercial benefits of synthesized vitamin production include superior quality, documentation, and the scalability and supply chain security required for large-scale finished goods manufacturing and sales planning.
- Quality & Safety
- Product development
- Science Papers
- Tutorial: Quality & Safety
Scalable capacity for mass-market production demands: Kappa’s current production capacity already exceeds the total projected yearly global vitamin K2 demand through 2020.
Industry-leading pricing: Kappa continuously reinvests in R&D and manufacturing processes to drive ingredient price points to levels that support commercial adoption. In 2017, Kappa led the market with a 45% price reduction – marking a significant step on the path to mass-market commercialization of K2.
Purity: all-trans vitamin K2 MK-7 (USP).
Quality: GMP, HACCP, ISO 22000:2005 manufacturing and distribution standards.
Stability: Patent-pending microencapsulation technology ensures stability in challenging formulations.
Long shelf life in finished products: 36 months shelf life on all ingredients; supported by extensive stability data on ingredients and finished formulations.
Approvals: Novel Food (EU), TGA (AUS), GRAS (USA), drug registration in India (2017). Application processes are initiated in countries including China, Thailand and others. Kosher and Halal certifications.
Kappa developed the K2 Formulation LookBook, including more than 120 ready-to-use product formulations and dosage forms targeted towards all K2 health applications and a wide range of consumer groups.
Kappa’s on-going ExperienceCard Program develops innovative vitamin K2 formulations in collaboration with industry leaders. Each ExperienceCard concept represents a novel product formulation that is specifically designed to solve an existing market problem or to address a health segment or consumer group in a new way. K2VITAL® vitamin K2 MK-7 provides the central ingredient in each of the products. Partners provided synergistic co-ingredients, innovative dosage or manufacturing technology, or other elements that make these forward-looking products possible.