• Women Over 50
• Osteoporosis

How Vitamin K Strengthens Our Bones

Learn all you need to know about the relation between vitamin K to osteoporosis and bone health.

Vitamin K is well-known for its role in blood clotting, but it also plays a critical part in bone health by participating in the activation of bone-related proteins, influencing the activity of bone-forming cells, and affecting bone resorption. Deficiency in vitamin K is relatively common due to its limited natural reserves and the need for dietary intake and absorption. Additionally, vitamin K deficiency can be exacerbated by the use of vitamin K antagonist anticoagulants like warfarin. Research indicates that low levels of vitamin K1, high levels of inactive osteocalcin, and poor dietary consumption of vitamins K1 and K2 correlate with an increased risk of bone fractures and reduced bone mineral density (BMD). While some studies suggest that vitamin K supplementation may lower fracture risks, there is a need for higher quality research focusing specifically on fractures as the primary outcome. Furthermore, the impact of using non-vitamin K antagonist oral anticoagulants instead of warfarin on fracture risks shows mixed results, with the current evidence being inconclusive and of varied quality.

Types of Vitamin K ^[1]

Vitamin K includes a group of fat-soluble compounds known for a common core structure, menadione, and varies by the type of side chain attached ^[2]. These differences define the three main forms:

• Vitamin K1 (Phylloquinone, PK) - This is the primary form of vitamin K found in the Western diet, mostly synthesized by plants and present in green leafy vegetables and other foods like vegetable oils, fruits, grains, and dairy.
• Vitamin K2 (Menaquinones, MKs) - Produced by certain bacteria, these compounds are categorized into 13 types (MK-2 to MK-14), based on the length of their side chains. Except for MK-4, these types are primarily synthesized by gut bacteria in humans or found in fermented foods like cheese and natto. Natto is notably rich in MK-7, which is highly effective and long-lasting in the body. Most K2 forms produced by the gut bacteria are weakly active.
• Vitamin K3 (Menadione) - This synthetic form lacks a side chain, making it water-soluble and added to animal feed. In animals, menadione is converted in specific tissues to MK-4, which is the main form of vitamin K in the human body. This conversion suggests that longer-chain K2 types may also transform into MK-4.

How Vitamin K Affects Bone

Vitamin K plays a crucial role in bone health through multiple mechanisms:

• Carboxylation of Proteins: Vitamin K is essential for the enzyme gamma-glutamyl carboxylase, which modifies certain proteins in the bone, transforming glutamic acid residues into a form that binds calcium. This process affects proteins like osteocalcin, which is important during bone mineralization. Osteocalcin binds calcium and helps regulate the size and shape of calcium deposits in bones. It's also involved in energy metabolism, marking bones as important players in hormone regulation and glucose management ^[3].
• Bone and Insulin Interaction: Insulin affects bone metabolism by promoting the formation of a less modified version of osteocalcin, which then participates in regulating blood sugar and insulin sensitivity. This interaction underscores the bone's role in overall metabolic health and how it interacts with hormones like insulin.
• Other Vitamin K-dependent Proteins: Matrix G1a protein, secreted by certain cells, helps prevent unwanted tissue calcification and promotes healthy blood vessel development. Protein S, known for its role in blood clotting, also contributes to bone turnover, although its exact function in bones is less clear.
• Regulation of Bone Cells and Genetic Factors: Beyond modifying proteins, Vitamin K helps control the activity of bone-forming cells and the genetic factors that dictate bone health. It suppresses bone breakdown and can influence the formation of cells responsible for bone resorption.
• Inflammation and Oxidative Stress: Studies suggest that certain forms of vitamin K can reduce inflammation and oxidative stress, which are detrimental to bone health.

In essence, vitamin K not only contributes to bone structure and health through its role in modifying proteins but also acts as a significant regulator of metabolic and genetic processes in bone tissue.

The effects of Vitamin K on Bone Mineral Density and Fractures

Research consistently shows that low levels of vitamin K1, high levels of undercarboxylated osteocalcin (a protein indicating vitamin K status), and low dietary intake of vitamins K1 and K2 are linked to a higher risk of bone fractures.

Several studies highlight the relationship between vitamin K intake and bone health. For instance, a 1999 significant study ^[4] observed that women consuming over 109 μg/day of vitamin K1 had a notably lower risk of hip fractures compared to those with lower intakes. This reduction in fracture risk was not observed at even higher intakes, suggesting there might be an optimal intake level beyond which no additional benefits are gained. Another large-scale review found a 22% reduction in fracture risk with high dietary vitamin K1 intake, although the results varied across studies.

However, the impact of vitamin K on bone mineral density (BMD) is less clear. Some studies, did not find a direct link between vitamin K1 intake and BMD, but did associate it with a lower risk of fractures, implying factors other than BMD might influence fracture risk. Other studies report inconsistent results regarding BMD, suggesting that dietary patterns and assessment methods might affect outcomes. For example, a study on Danish women ^[5] found no link between vitamin K1 intake and BMD, possibly due to lower intake levels compared to U.S. studies.

The challenges in these studies often relate to the methods used to assess vitamin K intake, typically food questionnaires, which may not accurately reflect true intake. These assessments tend to focus only on vitamin K1, which is predominant in the diet, potentially overlooking the effects of vitamin K2.

Additionally, while vitamin K intake is linked to certain bone health markers, like serum vitamin K levels and undercarboxylated osteocalcin, these markers do not consistently correlate with changes in BMD, complicating the understanding of vitamin K's role in bone health.

The effects of Vitamin K supplements on fractures and BMD

The research on vitamin K's effects on bone mineral density (BMD) and fracture risk has shown mixed results, depending on the type of vitamin K, the population studied, and the study's design.

Effects on BMD: A meta-analysis by Fang et al. reviewed studies on both healthy individuals and those with osteoporosis, finding no significant impact of vitamin K supplementation on femoral neck BMD but a notable increase in lumbar spine BMD, especially with vitamin K2 supplements. However, when breaking down the data, the results varied, showing significant benefits mainly in Asian populations and non-postmenopausal women. Another meta-analysis confirmed vitamin K2's positive effects on vertebral and forearm BMD in postmenopausal women with osteoporosis.

Beyond BMD: Some studies suggest that vitamin K's benefits might extend beyond just affecting BMD. For instance, studies by Knapen et al. indicated that while MK-4 supplementation didn't significantly increase BMD at the hip, it did improve other indicators of bone strength, such as mineral content and femoral neck width. Similarly, MK-7 supplements were found to slow the decline in BMD at specific sites and enhance bone strength.

Fracture Risk: Reviews focusing on fracture risk have shown that vitamin K, particularly MK-4, may reduce the risk of various types of fractures, with significant results reported in Japanese postmenopausal women. However, a study on bitherapy with MK-4 and calcium found no significant benefit in reducing vertebral fractures, except in a specific subgroup of women with multiple existing fractures.

In summary, while vitamin K supplements, especially K2, appear to offer some benefits in improving bone strength and reducing fracture risk in certain subgroups, inconsistencies across studies due to various limitations make it difficult to make definitive practice-changing recommendations. Further high-quality, targeted research is needed to clarify vitamin K's role in bone health more conclusively.

Conclusion

Vitamin K is essential for maintaining healthy bones. In observational studies, a low vitamin K intake, low serum vitamin K levels, and high ucOC concentrations are associated with an increased risk of fracture (particularly hip fracture). However, due to the lack of conclusive results from clinical trials, the use of vitamin K1 and K2 supplements remains controversial. The relationship between vitamin K and fracture risk must be elucidated through high-quality clinical trials involving patients who have inadequate dietary intake and/or low serum vitamin K levels.

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References

1. Rodríguez-Olleros Rodríguez C, Díaz Curiel M. Vitamin K and Bone Health: A Review on the Effects of Vitamin K Deficiency and Supplementation and the Effect of Non-Vitamin K Antagonist Oral Anticoagulants on Different Bone Parameters. J Osteoporos. 2019 Dec 31;2019:2069176. doi: 10.1155/2019/2069176. PMID: 31976057; PMCID: PMC6955144. [Open]

2. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008 Oct;100(4):530-47. PMID: 18841274. [Open]

3. Akbari S., Rasouli-Ghahroudi A. A. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. BioMed Research International. 2018;2018:8. doi: 10.1155/2018/4629383.4629383 [Open]

4. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999 Jan;69(1):74-9. doi: 10.1093/ajcn/69.1.74. PMID: 9925126. [Open]

5. Rejnmark L, Vestergaard P, Charles P, Hermann AP, Brot C, Eiken P, Mosekilde L. No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women. Osteoporos Int. 2006;17(8):1122-32. doi: 10.1007/s00198-005-0044-3. Epub 2006 May 9. PMID: 16683180. [Open]

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