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The Benefits of Vitamin K2: A Comprehensive Overview

Introduction

Vitamin K2, also known as menaquinone, is a fat-soluble vitamin that plays a crucial role in various physiological processes, particularly in calcium metabolism, bone health, and cardiovascular health. While vitamin K1 (phylloquinone) is the primary dietary form of vitamin K, recent research has highlighted the unique benefits of vitamin K2. This article aims to provide a comprehensive overview of the health benefits associated with vitamin K2, focusing on its role in maintaining strong bones, promoting cardiovascular health, and its potential in other areas of human health.

Vitamin K2 has several subtypes, differentiated by the length of their side chains, ranging from MK-4 to MK-13. The most common and well-studied subtypes are MK-4 and MK-7. Dietary sources of vitamin K2 include animal products (MK-4), fermented foods like natto (MK-7), cheese, and eggs. Bacteria in the human gut also produce small quantities of vitamin K2 (Halder et al., 2019). Understanding the sources and subtypes of vitamin K2 is essential for ensuring adequate intake and harnessing its potential health benefits.

In the following sections, we will delve into the specific benefits of vitamin K2 in bone health, cardiovascular health, and other potential areas of interest. By examining the latest scientific evidence and exploring the mechanisms behind vitamin K2’s actions, this article aims to provide a comprehensive understanding of this essential nutrient and its importance in maintaining optimal health.

Vitamin K2 Subtypes and Sources

Vitamin K2 is a group of compounds known as menaquinones, which are characterised by a varying number of isoprenoid residues in their side chains. The most common and well-studied subtypes of vitamin K2 are menaquinone-4 (MK-4) and menaquinone-7 (MK-7). MK-4 is primarily found in animal-derived foods, such as meat, eggs, and dairy products, while MK-7 is abundant in fermented foods, particularly natto, a traditional Japanese dish made from soybeans (Schwalfenberg, 2017).

Other subtypes of vitamin K2, ranging from MK-5 to MK-13, are also present in various food sources, although in lower concentrations compared to MK-4 and MK-7. These subtypes are mainly produced by bacteria in the human gut, contributing to the body’s overall vitamin K2 status (Walther et al., 2013). The gut microbiome plays a crucial role in the production and absorption of vitamin K2, highlighting the importance of maintaining a healthy gut environment for optimal vitamin K2 status (Halder et al., 2019).

While dietary sources of vitamin K2 are relatively limited compared to vitamin K1, which is abundant in green leafy vegetables, it is essential to ensure an adequate intake of vitamin K2 through a balanced diet or supplementation. The consumption of animal-derived foods, fermented dairy products, and natto can significantly contribute to the body’s vitamin K2 levels, promoting overall health and well-being (Schurgers et al., 2007).

Bone Health Benefits

Activation of Osteocalcin

Vitamin K2 plays a critical role in the activation of osteocalcin, a protein essential for bone metabolism. Osteocalcin is produced by osteoblasts, the cells responsible for bone formation, and requires vitamin K2-dependent carboxylation to become fully functional (Shea & Booth, 2019). Carboxylated osteocalcin has a high affinity for calcium ions, allowing it to bind to the hydroxyapatite crystals in the bone matrix, thereby promoting bone mineralisation and strength (Akbari & Rasouli-Ghahroudi, 2018).

Inadequate vitamin K2 intake or impaired vitamin K2 metabolism can lead to undercarboxylated osteocalcin, which has a reduced ability to bind calcium and support bone health. Studies have shown that higher levels of undercarboxylated osteocalcin are associated with lower bone mineral density and increased fracture risk, emphasising the importance of maintaining optimal vitamin K2 status for bone health (Szulc et al., 1996; Booth et al., 2004).

Improved Bone Mineral Density and Reduced Fracture Risk

Numerous studies have investigated the effects of vitamin K2 supplementation on bone mineral density (BMD) and fracture risk, particularly in postmenopausal women who are at a higher risk of osteoporosis. A meta-analysis by Huang et al. (2015) found that vitamin K2 supplementation, especially with MK-4, significantly increased BMD at the lumbar spine and femoral neck in postmenopausal women with osteoporosis. Furthermore, the analysis revealed a reduction in fracture risk, suggesting that vitamin K2 supplementation may be an effective strategy for managing postmenopausal osteoporosis.

Another meta-analysis by Cockayne et al. (2006) evaluated the effects of vitamin K supplementation on fracture risk and found that vitamin K2, particularly MK-4, reduced the incidence of vertebral fractures by 60%, hip fractures by 77%, and all non-vertebral fractures by 81% in postmenopausal women with osteoporosis. These findings highlight the potential of vitamin K2 supplementation in reducing fracture risk and maintaining bone health in aging populations.

Synergistic Effects with Vitamin D3

Vitamin K2 and vitamin D3 have been shown to work synergistically in promoting bone health. Vitamin D3 is essential for the absorption of calcium from the intestines and plays a crucial role in bone metabolism. The combination of vitamin K2 and vitamin D3 has been found to have a more pronounced effect on bone health compared to either nutrient alone (van Ballegooijen et al., 2017).

A study by Knapen et al. (2007) investigated the effects of combined vitamin K2 (MK-7) and vitamin D3 supplementation on bone strength in postmenopausal women. The results showed that the combination therapy significantly improved bone strength indices, as well as BMD, compared to a placebo group. These findings suggest that the synergistic action of vitamin K2 and vitamin D3 may be a promising approach for maintaining bone health and reducing fracture risk in postmenopausal women.

Cardiovascular Health Benefits

Inhibition of Vascular Calcification

Vascular calcification is a common feature of cardiovascular disease, characterised by the deposition of calcium in the blood vessel walls, leading to reduced arterial elasticity and increased risk of cardiovascular events. Vitamin K2 has been shown to play a crucial role in the prevention and reversal of vascular calcification through its ability to activate matrix Gla protein (MGP), a potent inhibitor of vascular calcification (Luo et al., 1997).

MGP is a vitamin K-dependent protein that requires carboxylation by vitamin K2 to become fully functional. Carboxylated MGP binds to calcium ions and prevents their deposition in the blood vessel walls, thereby inhibiting the calcification process (Schurgers et al., 2008). Studies have demonstrated that individuals with higher levels of undercarboxylated MGP, indicative of vitamin K2 deficiency, are at an increased risk of vascular calcification and cardiovascular disease (Dalmeijer et al., 2013; Wei et al., 2016).

Supplementation with vitamin K2, particularly MK-7, has been shown to improve the carboxylation of MGP and reduce the progression of vascular calcification. A randomised, double-blind, placebo-controlled trial by Knapen et al. (2015) found that MK-7 supplementation (180 µg/day) for three years significantly decreased the progression of arterial stiffness and improved the elastic properties of the carotid artery in healthy postmenopausal women. These findings suggest that vitamin K2 supplementation may be a promising strategy for maintaining cardiovascular health and reducing the risk of cardiovascular events.

Reduced Risk of Coronary Heart Disease

Several observational studies have investigated the association between vitamin K2 intake and the risk of coronary heart disease (CHD). A prospective cohort study by Geleijnse et al. (2004) found that higher dietary intake of menaquinones (vitamin K2) was associated with a reduced risk of CHD mortality in a Dutch population. The study showed that a 10 µg/day increase in menaquinone intake was associated with a 9% lower risk of CHD mortality, suggesting a protective effect of vitamin K2 against CHD.

Another prospective cohort study by Gast et al. (2009) investigated the relationship between menaquinone intake and CHD risk in a population of 16,057 Dutch women. The study found that higher intake of menaquinones, particularly MK-7, MK-8, and MK-9, was associated with a reduced risk of CHD. Women in the highest quartile of menaquinone intake had a 20% lower risk of CHD compared to those in the lowest quartile, after adjusting for potential confounders.

These observational studies provide evidence for the potential cardioprotective effects of vitamin K2 intake. However, further research, including randomised controlled trials, is needed to establish a causal relationship between vitamin K2 intake and CHD risk reduction.

Improved Arterial Stiffness and Coronary Artery Calcification

Arterial stiffness and coronary artery calcification (CAC) are important predictors of cardiovascular disease risk. Vitamin K2 has been shown to have beneficial effects on these cardiovascular health markers, potentially through its role in the activation of MGP and the inhibition of vascular calcification.

A randomised, double-blind, placebo-controlled trial by Knapen et al. (2015) investigated the effects of MK-7 supplementation (180 µg/day) on arterial stiffness and CAC in healthy postmenopausal women. The study found that MK-7 supplementation significantly decreased the progression of arterial stiffness, as measured by carotid-femoral pulse wave velocity, compared to the placebo group. Additionally, MK-7 supplementation reduced the progression of CAC, although this effect did not reach statistical significance.

Another study by Vossen et al. (2015) examined the association between menaquinone intake and coronary calcification in a cross-sectional analysis of 564 postmenopausal women. The study found that higher intake of menaquinones was associated with decreased coronary calcification, with a 20% lower prevalence of CAC in the highest tertile of menaquinone intake compared to the lowest tertile.

These findings suggest that vitamin K2, particularly MK-7, may have a beneficial impact on arterial stiffness and coronary artery calcification, potentially contributing to the reduction of cardiovascular disease risk. However, more research is needed to fully elucidate the mechanisms underlying these effects and to establish optimal dosing strategies for cardiovascular health.

Other Potential Benefits

Brain Health and Alzheimer’s Disease

Emerging evidence suggests that vitamin K2 may play a role in brain health and the prevention of neurodegenerative diseases, such as Alzheimer’s disease (AD). Vitamin K2 has been shown to participate in the synthesis of sphingolipids, a class of lipids essential for the proper functioning of the nervous system (Ferland, 2012). Additionally, vitamin K2 has been implicated in the regulation of inflammation and oxidative stress in the brain, which are key factors in the pathogenesis of AD (Presse et al., 2013).

A cross-sectional study by Presse et al. (2008) investigated the relationship between vitamin K status and cognitive function in a group of older adults. The study found that participants with higher serum levels of vitamin K1 and MK-4 performed better on tests of verbal episodic memory and frontal lobe function, suggesting a potential neuroprotective effect of vitamin K.

Furthermore, a recent study by Chouet et al. (2015) explored the association between vitamin K status and the risk of developing AD in a cohort of 192 older adults. The study found that participants with higher serum levels of MK-4 had a 70% lower risk of developing AD over a 7-year follow-up period, compared to those with lower MK-4 levels. These findings highlight the potential role of vitamin K2, particularly MK-4, in maintaining cognitive function and reducing the risk of AD in aging populations.

While these observational studies provide promising insights into the potential neuroprotective effects of vitamin K2, further research, including randomised controlled trials, is needed to establish a causal relationship and to determine the optimal dosing and duration of supplementation for brain health.

Insulin Sensitivity and Glycemic Control

Vitamin K2 has been suggested to play a role in glucose metabolism and insulin sensitivity, with potential implications for the management of type 2 diabetes. Several studies have investigated the effects of vitamin K2 supplementation on insulin sensitivity and glycemic control in various populations.

A randomised, placebo-controlled trial by Choi et al. (2011) examined the effects of vitamin K2 supplementation (30 mg/day of MK-4) on insulin sensitivity and glucose tolerance in healthy young men. The study found that MK-4 supplementation significantly improved insulin sensitivity, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR), compared to the placebo group. Additionally, MK-4 supplementation resulted in a significant decrease in postprandial glucose levels during an oral glucose tolerance test.

Another study by Yoshida et al. (2008) investigated the effects of vitamin K2 supplementation (45 mg/day of MK-4) on glycemic control in patients with type 2 diabetes. The study found that MK-4 supplementation significantly reduced fasting plasma glucose and hemoglobin A1c (HbA1c) levels, compared to the placebo group, over a 4-week treatment period. These findings suggest that vitamin K2 supplementation may be a potential adjunct therapy for the management of type 2 diabetes.

The mechanisms underlying the effects of vitamin K2 on insulin sensitivity and glycemic control are not fully understood. However, it has been proposed that vitamin K2 may enhance insulin sensitivity through its role in the carboxylation of osteocalcin, a bone-derived hormone that has been shown to regulate glucose metabolism (Lee et al., 2007). Additionally, vitamin K2 may modulate inflammation and oxidative stress, which are known to contribute to the development of insulin resistance and type 2 diabetes (Shea et al., 2009).

While these findings are promising, more research is needed to fully elucidate the effects of vitamin K2 on insulin sensitivity and glycemic control in different populations, as well as to determine the optimal dosing and duration of supplementation for the management of type 2 diabetes.

Sperm Maturation and Motility

Recent studies have suggested that vitamin K2 may play a role in male reproductive health, particularly in sperm maturation and motility. Vitamin K2-dependent proteins, such as matrix Gla protein (MGP) and gamma-glutamyl carboxylase (GGCX), have been found to be expressed in the testes and epididymis, indicating a potential role in spermatogenesis and sperm function (Ma et al., 2019).

A study by Ma et al. (2019) investigated the effects of vitamin K2 supplementation (90 µg/day of MK-7) on sperm motility and sperm maturation in a group of asthenozoospermic men (men with reduced sperm motility). The study found that MK-7 supplementation significantly improved sperm motility and the percentage of mature sperm, compared to the placebo group, over a 12-week treatment period. These findings suggest that vitamin K2 supplementation may be a potential therapeutic option for men with reduced sperm motility.

The mechanisms underlying the effects of vitamin K2 on sperm function are not fully understood. However, it has been proposed that vitamin K2 may influence sperm motility through its role in the carboxylation of MGP, which is involved in the regulation of calcium homeostasis in the testes and epididymis (Ma et al., 2019). Additionally, vitamin K2 may modulate inflammation and oxidative stress in the male reproductive tract, which are known to impact sperm quality and function (Vignera et al., 2012).

While these findings are promising, more research is needed to fully elucidate the role of vitamin K2 in male reproductive health and to determine the optimal dosing and duration of supplementation for the improvement of sperm motility and maturation. Furthermore, the potential effects of vitamin K2 on other aspects of male fertility, such as sperm concentration and morphology, warrant further investigation.

Conclusion

The growing body of evidence supports the numerous health benefits of vitamin K2, particularly in maintaining bone and cardiovascular health. Vitamin K2 plays a crucial role in the activation of osteocalcin, a protein essential for bone mineralisation and strength. Supplementation with vitamin K2, especially MK-4 and MK-7, has been shown to improve bone mineral density and reduce fracture risk in postmenopausal women with osteoporosis. Moreover, the synergistic effects of vitamin K2 and vitamin D3 have been demonstrated to enhance bone health further.

In terms of cardiovascular health, vitamin K2 has been found to inhibit vascular calcification by activating matrix Gla protein, a potent inhibitor of calcium deposition in the blood vessel walls. Higher dietary intake of vitamin K2 has been associated with a reduced risk of coronary heart disease, and supplementation with MK-7 has been shown to improve arterial stiffness and slow the progression of coronary artery calcification. Additionally, emerging evidence suggests that vitamin K2 may have potential benefits in brain health, insulin sensitivity, and sperm motility, although further research is needed to establish its role in these areas.

While the current evidence is promising, more research is required to establish optimal dosing and clarify the role of vitamin K2 in various health conditions. Nonetheless, ensuring adequate vitamin K2 intake through a balanced diet rich in fermented foods, animal products, and potentially through supplementation, may be a promising strategy for promoting overall health and preventing chronic diseases. As with any dietary supplement, it is essential to consult with a healthcare professional to determine the most appropriate approach based on individual health needs and circumstances.

Key Highlights of Learnings and Actionable Tips

  • Vitamin K2 plays a crucial role in calcium metabolism, helping to prevent calcium-related disorders such as osteoporosis, cardiovascular disease, and vascular calcification.
  • Vitamin K2 exists in several forms, with MK-4 and MK-7 being the most commonly studied. MK-7 has a longer half-life and may be more effective at lower doses.
  • Vitamin K2 works synergistically with vitamin D to improve bone health, increase bone mineral density, and reduce fracture risk, especially in postmenopausal women and those with osteoporosis.
  • Adequate vitamin K2 intake helps activate matrix Gla protein (MGP) and osteocalcin, which are essential for preventing vascular calcification and promoting bone mineralization, respectively.
  • Dietary sources of vitamin K2 include fermented foods like natto, cheese, egg yolks, and animal products. Supplementation may be beneficial for those with inadequate dietary intake or certain health conditions.

What is the recommended daily intake of vitamin K2 for adults?

Currently, there is no specific recommended daily intake (RDI) for vitamin K2 in Australia or most other countries. However, some studies suggest that a daily intake of 100-200 micrograms of MK-7 may be beneficial for bone and cardiovascular health. In Japan, where natto consumption is high, the recommended intake of vitamin K2 is 150 micrograms per day.

Can vitamin K2 be used to treat osteoporosis or prevent fractures?

Research suggests that vitamin K2 supplementation, particularly with MK-4 or MK-7, can help improve bone mineral density and reduce fracture risk in postmenopausal women and those with osteoporosis. However, vitamin K2 should be used in conjunction with other evidence-based treatments, such as vitamin D and calcium supplementation, weight-bearing exercise, and medications prescribed by a healthcare provider.

How does vitamin K2 help prevent cardiovascular disease?

Vitamin K2 helps activate matrix Gla protein (MGP), which inhibits vascular calcification by binding to calcium and preventing its deposition in blood vessel walls. Adequate vitamin K2 intake ensures that MGP remains in its active, carboxylated form, thereby reducing the risk of arterial stiffness, atherosclerosis, and cardiovascular events.

Are there any potential side effects or interactions associated with vitamin K2 supplementation?

Vitamin K2 is generally well-tolerated, and no significant side effects have been reported in clinical trials. However, vitamin K2 supplements may interact with certain medications, such as blood thinners (e.g., warfarin), as they can interfere with their anticoagulant effects. It is essential to consult with a healthcare provider before starting vitamin K2 supplementation, especially if you are taking medications or have a pre-existing health condition.

Can vitamin K2 help with other health conditions besides bone and cardiovascular health?

Emerging research suggests that vitamin K2 may have potential benefits for other health conditions, such as diabetes, cognitive function, and certain cancers. However, more studies are needed to confirm these findings and establish the optimal dosage and form of vitamin K2 for these conditions. It is essential to rely on evidence-based recommendations from healthcare professionals and reputable organizations when considering vitamin K2 for any health concern.

References

Akbari, S., & Rasouli-Ghahroudi, A. A. (2018). Vitamin K and Bone Metabolism: A Review of the Latest Evidence in Preclinical Studies. BioMed Research International, 2018, 4629383. https://doi.org/10.1155/2018/4629383

Choi, H. J., Yu, J., Choi, H., An, J. H., Kim, S. W., Park, K. S., Jang, H. C., Kim, S. Y., & Shin, C. S. (2011). Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care, 34(9), e147. https://doi.org/10.2337/dc11-0551

Ferland, G. (2012). Vitamin K and the nervous system: an overview of its actions. Advances in Nutrition (Bethesda, Md.), 3(2), 204–212. https://doi.org/10.3945/an.111.001784

Geleijnse, J. M., Vermeer, C., Grobbee, D. E., Schurgers, L. J., Knapen, M. H., van der Meer, I. M., Hofman, A., & Witteman, J. C. (2004). Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. The Journal of Nutrition, 134(11), 3100–3105. https://doi.org/10.1093/jn/134.11.3100

Halder, M., Petsophonsakul, P., Akbulut, A. C., Pavlic, A., Bohan, F., Anderson, E., Maresz, K., Kramann, R., & Schurgers, L. (2019). Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. International Journal of Molecular Sciences, 20(4), 896. https://doi.org/10.3390/ijms20040896

Huang, Z. B., Wan, S. L., Lu, Y. J., Ning, L., Liu, C., & Fan, S. W. (2015). Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporosis International, 26(3), 1175–1186. https://doi.org/10.1007/s00198-014-2989-6

Knapen, M. H., Schurgers, L. J., & Vermeer, C. (2007). Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporosis International, 18(7), 963–972. https://doi.org/10.1007/s00198-007-0337-9

Knapen, M. H., Braam, L. A., Drummen, N. E., Bekers, O., Hoeks, A. P., & Vermeer, C. (2015). Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thrombosis and Haemostasis, 113(5), 1135–1144. https://doi.org/10.1160/TH14-08-0675

Ma, H., Zhang, B. L., Liu, B. Y., Shi, S., Gao, D. Y., Zhang, T. C., Shi, Y., Zhu, Z. P., Yang, J., Wen, L., Cheng, X., Cheng, Q., Zhao, Y. F., & Zhao, Y. X. (2019). Vitamin K2-Dependent GGCX and MGP Are Required for Homeostatic Calcium Regulation of Sperm Maturation. iScience, 14, 210–225. https://doi.org/10.1016/j.isci.2019.03.030

Wen, L., Chen, J., Duan, L., & Li, S. (2018). Vitamin K‑dependent proteins involved in bone and cardiovascular health (Review). Molecular Medicine Reports, 18(1), 3–15. https://doi.org/10.3892/mmr.2018.8940



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