Zumpano helps us understand the health benefits of vitamin K2 and how to get more of it in your diet. What is vitamin K2? Think of vitamin K as a collection of vitamins that play a similar role in your health. That class is made up of vitamin K1, as well as vitamin K2 and vitamin K2’s 10 subtypes, known as MK-4 to MK-13.

Shearer, Martin J.; Newman, Paul (March 2014). "Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis". Journal of Lipid Research. 55 (3): 345–362. doi: 10.1194/jlr.R045559. ISSN 0022-2275. PMC 3934721. PMID 24489112.

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Vitamin K1 comes from plant sources, like leafy greens and blueberries. While vitamin K2 is more common in animal products, fermented foods and some kinds of cheese. It stays in your body longer than vitamin K1 and holds the potential for some serious health benefits that are just now starting to come to light.

Vitamin K2 is often found in animal products and fermented foods, as opposed to natural, plant food sources,” Zumpano notes. “But that’s not a hard-and-fast rule. There are some foods that are both naturally healthy and rich in vitamin K2.” Interestingly, there is also substantial evidence from controlled studies that K2 may provide major benefits for bone health. In addition to its positive effects on blood clotting and strong bones, vitamin K helps keeps your heart healthy. That’s because of the way it acts to clear out calcium from your blood vessels. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2017). "Dietary reference values for vitamin K". EFSA J. 15 (5): e04780 See 2.2.1. Biochemical functions. doi: 10.2903/j.efsa.2017.4780. PMC 7010012. PMID 32625486.In a 2019 meta-analysis of 21 studies and 222,592 participants, an increased dietary intake of either vitamin K1 or K2 was linked with a moderately reduced risk of coronary heart disease, although not with mortality ( 8). Zieman SJ, Melenovsky V, Kass DA (May 2005). "Mechanisms, pathophysiology, and therapy of arterial stiffness". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (5): 932–43. doi: 10.1161/01.atv.0000160548.78317.29. PMID 15731494. Seven of these trials, which took fractures into consideration, found that vitamin K2 reduced spinal fractures by 60%, hip fractures by 77%, and all non-spinal fractures by 81% ( 12).

There’s still much to be understood about the differences between vitamin K1 and vitamin K2, and research is ongoing. Zumpano details what we do know about K vitamins, and vitamin K2 specifically, including some of its most important benefits. Aids in blood clotting People taking blood thinning medications like Warfarin are counseled to keep their vitamin K intake consistent and avoid large quantities of vitamin K-rich foods or large fluctuations in vitamin K intake.Currently, liquid fermented products enjoy the favor of commercial markets. Several modifications have been researched in LSF for the fermentation media or the microbial strain or mechanical design to improve the vitamin K2-7 yield and reduce the fermentation time. Mainly Bacillus species including B. subtilis and B. licheniformis are studied for LSF ( Mahdinia et al., 2017). Morishita et al. ( Morishita et al., 1999) used lactic acid bacteria for the production of all vitamin K2 forms. Leuconostoc lactis and Lactococcus strains including L. lactis ssp. lactis and L. lactis ssp. cremoris produced quinones when grown on medium containing soy milk. Therefore, these strains are used as starter cultures in dairy ( Morishita et al., 1999). At this point, researchers have yet to determine if vitamin K1 or vitamin K2 are equally responsible for clotting or if one is any more effective than the other when it comes to blood clotting. Builds healthy bones Though this needs to be studied in more detail, current research on vitamin K2 and health is promising. In fact, it potentially may have lifesaving implications for many people. Summary Tsukamoto Y, Ichise H, Kakuda H, Yamaguchi M (2000). "Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals". Journal of Bone and Mineral Metabolism. 18 (4): 216–22. doi: 10.1007/s007740070023. PMID 10874601. S2CID 24024697.

To estimate the effective dose of MK-7, Theuwissen et al. conducted a double blind, randomized, controlled study including 42 Dutch participants who were divided into seven groups and were administered with supplements (capsules) of placebo or different concentrations of MK-7 (10, 20, 45, 90, 180 or 360µg) daily for 3months. The plasma concentration range of MK-7 for the groups administered with 10, 20, 45, 90, 180 and 360µg were reported to be 0–0.5, 0.4–2.1, 0–1.6, 0.4–4.6, 0.5–4.2, 1.1–6.5 and 4.1–10.6ng/ml, respectively, thus indicating a direct correlation between plasma MK-7 concentration and MK-7 supplementation. Intake of 90µg or more per day resulted in a significant increase in circulating concentrations as compared to placebo. Further, it was reported that MK-7 supplements at concentrations around recommended dietary allowance (RDA = 75µg) ( Theuwissen et al., 2012) enhanced carboxylation of matrix Gla protein (MGP) and osteocalcin (OC), while a decrease in the levels of circulating dephospho-uncarboxylayed MGP (dp-ucMGP) and uncarboxylated osteocalcin (ucOC) as well as in the ucOC:cOC ratio was observed. Following the highest intake of MK-7, the level of circulating cOC was significantly increased. No significant effects were observed on the circulating levels of osteocalcin and MGP at supplementation doses of MK-7 below RDA. a b Shearer MJ, Newman P (October 2008). "Metabolism and cell biology of vitamin K". Thrombosis and Haemostasis. 100 (4): 530–47. doi: 10.1160/th08-03-0147. PMID 18841274. S2CID 7743991. Still, there is a highly believable biological mechanism for its effectiveness and strong positive correlations with heart health in observational studies. SummaryA randomized controlled trial was conducted by Sakak et al. ( Rahimi Sakak et al., 2021) on 68 patients with type 2 diabetes on oral glucose-lowering therapy. Patients were either administered 360μg of MK-7 or placebo daily for 12weeks. No significant difference in the atherogenic status between the MK-7 or placebo group was observed. Hence, it was concluded that 360μg of MK-7 supplementation for 12weeks cannot improve the insulin resistant (IR)-related indexes of cardiovascular risk ( Rahimi Sakak et al., 2021). Also, a randomized, double-blind placebo-controlled trial was performed to assess whether the supplementation of menaquinone-7 decreases vascular calcification in patients having type 2 diabetes and cardiovascular disease (CVD). Sixty-eight patients were randomly administered either with 360μg daily of MK-7 or placebo for 6months. Blood samples of the patients administered with MK-7 showed increased active calcification compared with placebo when measured with 18sodium fluoride positron emission tomography ( 18F-Na PET) activity; however, no effect was found in calcification mass on conventional computed tomography (CT) ( Zwakenberg et al., 2019). Vitamins A and D are also believed to play an important role here, working synergistically with vitamin K2 ( 17). Summary An experiment was performed by Brugè et al. to study the effect of K2-7 supplementation with extra-virgin olive oil on carboxylation of OC. Olive oil enriched with 45 or 90µg of K2-7 was administered for 2weeks in 12 healthy volunteers in Italy. The results demonstrated significant increase in cOC:ucOC ratio with 90µg of K2-7 which improves bone mineralization; however, olive oil with 45µg K2-7 did not show a biological effect. Hence, it was concluded that extra-virgin olive oil enriched with K2-7 can improve bone mineralization ( Brugè et al., 2011). Dalmeijer et al. ( Dalmeijer et al., 2012) conducted a randomized double-blind placebo-controlled study for 12weeks to investigate the effect of K2-7 on carboxylation of matrix Gla protein (MGP). Sixty patients that were administered with 180 or 360µg showed dose-dependent decrease in dp-ucMGP; however, no change was observed in dp-cMGP and total ucMGP level ( Dalmeijer et al., 2012).