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PHYLLOQUINONE

Also known as: Vitamin K1, phytonadione, phytomenadione, Phylloquinone

Overview

Phylloquinone, also known as vitamin K1, is a fat-soluble vitamin predominantly found in green leafy vegetables such as spinach, kale, and broccoli. It is a crucial nutrient involved in several physiological processes, most notably blood clotting and bone metabolism. As the primary dietary form of vitamin K, phylloquinone is distinct from vitamin K2 (menaquinones), which are synthesized by gut bacteria and present in fermented foods. Its main applications include preventing and treating vitamin K deficiency, supporting bone health, and potentially contributing to cardiovascular health by modulating vascular calcification. Research on phylloquinone is extensive, with numerous randomized controlled trials and meta-analyses supporting its roles, particularly in bone health and fracture prevention. The evidence quality for bone-related outcomes is generally moderate to high, while its cardiovascular effects are an area of emerging research.

Benefits

Phylloquinone offers several evidence-based benefits, primarily in bone and cardiovascular health: - **Bone Health and Fracture Prevention:** A systematic review and meta-analysis of randomized controlled trials (RCTs) indicated that vitamin K1 supplementation can modestly reduce fracture risk and improve bone mineral density. This benefit is particularly noted in postmenopausal women and elderly populations, with statistically significant, albeit modest, reductions in fracture incidence observed after at least 6 months of supplementation. The evidence quality for this benefit is considered moderate to high. - **Cardiovascular Health and Vascular Calcification:** Emerging research, including systematic reviews and meta-analyses, suggests that phylloquinone supplementation may slow the progression of coronary artery calcification (CAC). Studies have shown significant reductions in inactive matrix Gla-protein (dp-ucMGP), a biomarker of vitamin K deficiency and vascular calcification, following vitamin K supplementation. While these findings suggest improved vascular health, clinical outcome data on major cardiovascular events remain mixed. Some studies link low phylloquinone levels to increased cardiovascular risk in specific groups (e.g., hypertensive elderly), but direct supplementation effects on clinical outcomes require further robust investigation. The evidence quality for this benefit is emerging and moderate.

How it works

Phylloquinone functions as an essential cofactor for the enzyme gamma-glutamyl carboxylase. This enzyme is responsible for activating vitamin K-dependent proteins through the carboxylation of specific glutamate residues. This activation is critical for several bodily functions: - **Blood Coagulation:** Phylloquinone activates clotting factors II, VII, IX, and X, which are vital for the blood clotting cascade. - **Bone Metabolism:** It activates osteocalcin, a protein that binds calcium within the bone matrix, thereby promoting proper bone mineralization and strength. - **Vascular Health:** Phylloquinone activates matrix Gla-protein (MGP), which plays a crucial role in inhibiting the calcification of blood vessels. Phylloquinone is absorbed in the small intestine, requiring the presence of bile salts, and is then transported via chylomicrons through the lymphatic system. Its bioavailability is enhanced by dietary fat intake.

Side effects

Phylloquinone supplementation is generally considered safe and well-tolerated, with a strong safety record at therapeutic doses. Adverse events are rare and typically mild. - **Common Side Effects:** Mild gastrointestinal discomfort is occasionally reported but is uncommon. - **Uncommon/Rare Side Effects:** Hypersensitivity reactions are exceedingly rare. - **Drug Interactions:** The most significant interaction is with vitamin K antagonists, such as warfarin. Phylloquinone can antagonize the anticoagulant effects of these medications, necessitating careful monitoring of coagulation parameters (e.g., INR) and potential dose adjustments of the anticoagulant when phylloquinone supplementation is initiated or changed. Patients on warfarin or similar drugs should consult their healthcare provider before taking phylloquinone. - **Contraindications:** While generally safe, caution is advised in patients with pre-existing bleeding disorders due to its role in coagulation. There are no absolute contraindications at typical supplemental doses. - **Special Populations:** Phylloquinone is considered safe for use during pregnancy and lactation when administered appropriately. However, as with any supplement, individuals with specific medical conditions should consult a healthcare professional.

Dosage

The recommended dosage of phylloquinone varies depending on the intended purpose and individual needs. For general supplementation, a minimum effective dose typically ranges from 100 to 200 micrograms (mcg) per day. For specific benefits, such as bone health, studies have often utilized dosages between 100 and 500 mcg per day. There is no established upper limit for phylloquinone, and doses up to several milligrams daily have been safely used in clinical trials without significant adverse effects. To optimize absorption, phylloquinone, being a fat-soluble vitamin, should be taken with meals that contain some dietary fat. Oral formulations are standard for supplementation, while injectable forms are primarily used in clinical settings for severe deficiency or acute bleeding. Individuals with malabsorption syndromes may have reduced bioavailability and may require higher doses or alternative administration routes. Adequate intake of vitamin D and calcium may synergistically enhance the bone health benefits of phylloquinone.

FAQs

Is phylloquinone safe for long-term use?

Yes, phylloquinone is generally considered safe for long-term use when taken within recommended dosage guidelines. It has a strong safety profile with minimal side effects.

Can it be taken with blood thinners?

Phylloquinone can interfere with the action of vitamin K antagonist blood thinners like warfarin. If you are on such medication, consult your doctor for monitoring and potential dose adjustments.

How soon do benefits appear?

Benefits related to bone health, such as improved bone mineral density, typically require at least 6 months of consistent supplementation to become noticeable. Vascular effects may also take time to manifest.

Does it help with cardiovascular disease?

While evidence suggests phylloquinone may help slow vascular calcification, a marker of cardiovascular risk, definitive clinical outcome data on preventing cardiovascular events are still emerging and mixed.

Research Sources

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/410550 – This systematic review and meta-analysis of RCTs found that vitamin K1 supplementation modestly reduced fracture incidence and improved bone mineral density in adults, particularly in postmenopausal women and the elderly. The study included trials with at least 6 months of treatment and noted some heterogeneity but maintained high quality.
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1115069/full – This systematic review of seven RCTs demonstrated that vitamin K supplementation significantly reduced inactive matrix Gla-protein (dp-ucMGP) levels and slowed the progression of coronary artery calcification. The study reported no significant difference in adverse events compared to controls, indicating a moderate to high quality of evidence.
https://openheart.bmj.com/content/8/2/e001715 – This systematic review and meta-analysis highlighted associations between low vitamin K status, including phylloquinone, and increased cardiovascular mortality. It presented mixed results on direct supplementation effects but emphasized the role of inactive MGP as a biomarker, with moderate quality evidence including some observational data.