Vitamin K as phytonadione
Also known as: Phytonadione, Vitamin K1, Phylloquinone, Konakion
Overview
Phytonadione, also known as vitamin K1 or phylloquinone, is a fat-soluble vitamin essential for blood coagulation and bone health. It acts as a cofactor for the enzyme γ-glutamyl carboxylase, which is crucial for the activation of clotting factors (II, VII, IX, X) and proteins like osteocalcin and matrix Gla protein (MGP). Natural sources of phytonadione include leafy green vegetables such as kale and spinach, as well as broccoli and vegetable oils. While primarily recognized for its role in reversing anticoagulant effects, particularly warfarin toxicity, emerging research suggests potential benefits in osteoporosis prevention. The bioavailability of synthetic phytonadione in supplements is generally higher than that of dietary K1 due to its emulsified form. Research on phytonadione is well-established for coagulation, with moderate evidence supporting its role in reducing bone loss, but limited evidence for fracture prevention and cardiovascular benefits.
Benefits
Phytonadione demonstrates potential benefits for bone health. Specifically, it has been shown to reduce bone turnover markers, such as urinary NTx, and improve bone mineral density (BMD) in postmenopausal women. However, evidence regarding fracture risk reduction is mixed. A 2006 meta-analysis indicated no significant fracture reduction with phytonadione supplementation. For cardiovascular health, direct evidence for phytonadione's effects on vascular calcification is limited, with stronger evidence supporting the role of menaquinone (K2) in slowing coronary artery calcification (CAC) progression. A 2024 meta-analysis found no significant impact of phytonadione on blood pressure, C-reactive protein (CRP), or body mass index (BMI).
How it works
Phytonadione functions primarily as a cofactor for γ-glutamyl carboxylase, an enzyme responsible for the post-translational modification of several proteins. This modification, known as γ-carboxylation, is essential for activating proteins involved in blood clotting, such as factors II, VII, IX, and X, as well as bone-related proteins like osteocalcin and matrix Gla protein (MGP). These proteins require γ-carboxylation to bind calcium and perform their respective functions. Phytonadione absorption ranges from 10% to 80% and is enhanced when consumed with dietary fats. The synthetic form of phytonadione found in supplements generally exhibits higher bioavailability than dietary K1 due to its emulsification.
Side effects
At dietary doses, phytonadione is generally well-tolerated, with rare side effects. However, high doses exceeding 5 mg per day may cause flushing or dysgeusia (altered taste). Drug interactions are a significant concern, particularly with warfarin, as phytonadione antagonizes its anticoagulant effects, necessitating careful INR monitoring. Bile acid sequestrants can reduce phytonadione absorption, potentially diminishing its effectiveness. Contraindications include severe hepatic impairment and hypersensitivity to any components of the phytonadione formulation. It is crucial to exercise caution and seek medical supervision when using phytonadione, especially in individuals with pre-existing medical conditions or those taking medications that may interact with vitamin K1.
Dosage
The minimum effective dose of phytonadione for reducing bone turnover is approximately 0.5–1 mg per day. The optimal dosage range typically falls between 1–10 mg per day, although higher doses may be used under medical supervision for specific conditions like warfarin reversal. For optimal absorption, phytonadione should be taken with meals containing at least 10 grams of fat. Vitamin D can act as a cofactor, enhancing osteocalcin activation when taken in conjunction with phytonadione. While specific upper limits for phytonadione intake have not been definitively established, it is advisable to adhere to recommended dosage ranges and consult with a healthcare professional to determine the appropriate dosage based on individual needs and medical conditions.
FAQs
Does phytonadione prevent fractures?
Evidence is inconsistent. While phytonadione may reduce bone loss, studies have not consistently demonstrated a significant reduction in fracture risk across diverse populations. More research is needed to clarify its role in fracture prevention.
Is phytonadione safe to take with blood thinners?
Phytonadione is contraindicated for individuals on warfarin without medical supervision due to its interaction with the anticoagulant. It can reverse the effects of warfarin, requiring careful monitoring of INR levels to maintain therapeutic anticoagulation.
How long does it take to see benefits from phytonadione supplementation?
Improvements in bone turnover markers may be observed within 3–6 months of supplementation. However, assessing the impact on fracture risk typically requires a longer follow-up period, often two years or more, to detect meaningful changes.
What foods are high in Vitamin K1?
Leafy green vegetables such as spinach, kale, collard greens, and broccoli are excellent sources of vitamin K1. Certain vegetable oils, like soybean and canola oil, also contain significant amounts of phytonadione.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/16801507/ – This systematic review and meta-analysis of 7 RCTs (n=1,407) investigated the effect of phytonadione on bone health. The findings indicated that phytonadione reduced bone loss but did not significantly reduce fracture risk (OR 0.40, 95% CI 0.15–1.07). The authors noted limitations including heterogeneous populations and short follow-up periods (1–3 years).
- https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1115069/full – This systematic review, encompassing 12 studies, explored the role of vitamin K in cardiovascular health, particularly in slowing coronary artery calcification (CAC) progression. The review highlighted that vitamin K, primarily K2, exhibited a potential benefit in slowing CAC progression. However, the review noted a lack of phytonadione-specific data, limiting conclusions about K1's direct effects.
- https://www.cambridge.org/core/journals/journal-of-nutritional-science/article/effect-of-vitamin-k-supplementation-on-cardiovascular-risk-factors-a-systematic-review-and-metaanalysis/0F16EF6952E35875EE28AC0DA5974B5E – This meta-analysis of 17 RCTs examined the effect of vitamin K supplementation on cardiovascular risk factors. The study found no significant effect of vitamin K supplementation on blood pressure, C-reactive protein (CRP), or body mass index (BMI). The authors noted that the included studies used mixed K1/K2 formulations, which could influence the results.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6418499/ – This article discusses the role of vitamin K in bone health and its potential benefits in preventing osteoporosis. It highlights the importance of vitamin K in the carboxylation of osteocalcin, a protein involved in bone mineralization. The article suggests that vitamin K supplementation may improve bone mineral density and reduce the risk of fractures, particularly in postmenopausal women.
- https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/410550 – This article discusses the role of vitamin K in blood clotting and its use in reversing the effects of warfarin. It explains how vitamin K is essential for the synthesis of clotting factors in the liver and how it can be used to counteract excessive anticoagulation. The article emphasizes the importance of monitoring INR levels when using vitamin K to manage warfarin therapy.
