Vitamin K1 (Phylloquinone) | Supplementopedia

Overview

Vitamin K1 (phylloquinone) is a fat-soluble micronutrient belonging to the vitamin K family.
It is primarily obtained from plant sources.
It serves as an essential co-factor for the γ-carboxylation of specific glutamate residues in proteins.
This reaction is critical for the biological activity of several clotting factors and other calcium-binding proteins.
Its principal physiological role is to enable normal blood coagulation.
It supports the proper deposition of calcium in bone and vascular tissue.

Adequate vitamin K1 intake supports hemostasis by activating clotting factors II, VII, IX, and X, thereby reducing bleeding risk after surgery or trauma.
Higher dietary phylloquinone intake is linked with improved bone mineral density and lower fracture risk, especially in post-menopausal women, likely through osteocalcin activation.
Vitamin K1 may modestly improve insulin sensitivity and reduce arterial calcification, contributing to cardiovascular health.
Higher intake is associated with lower rates of cognitive decline in older adults.
The strongest evidence base is for coagulation and bone health, while metabolic and neuro-protective effects remain an active research area.

Vitamin K1 functions as a catalytic co-factor for the enzyme γ-glutamyl carboxylase.
This enzyme converts specific glutamate residues in target proteins to γ-carboxyglutamate (Gla) residues.
This post-translational modification creates high-affinity calcium-binding sites.
These sites are essential for the biological activity of clotting factors (II, VII, IX, X), anticoagulant proteins C and S, and bone matrix proteins such as osteocalcin and matrix Gla-protein (MGP).
The Gla residues enable these proteins to bind calcium ions.
This facilitates fibrin formation, mineralization of bone, and inhibition of ectopic calcification in vessels.
Vitamin K1 is recycled via the vitamin K cycle.
The vitamin K epoxide reductase complex (VKORC1) reduces the oxidized vitamin back to its active hydroquinone form, allowing continuous enzymatic activity.

The Institute of Medicine sets the Adequate Intake (AI) for adults at 90 µg/day for women and 120 µg/day for men.
Most multivitamins provide 80–150 µg of phylloquinone.
Clinical studies investigating bone or cardiovascular outcomes commonly employ 180–300 µg/day.
Short-term post-surgical protocols may use 1–2 mg/day under medical supervision.
Vitamin K1 is best taken with a fat-containing meal to enhance absorption.
For individuals on warfarin, any supplemental vitamin K should be introduced gradually and under physician guidance to maintain stable anticoagulation.
Pregnant and lactating women may safely use up to 150 µg/day, aligned with the AI, unless otherwise directed by a clinician.

Vitamin K1 is considered safe at dietary and supplemental levels.
The tolerable upper intake level has not been established due to low toxicity.
Reported adverse effects are rare but may include gastrointestinal upset or allergic skin reactions.
The primary contraindication is for individuals taking vitamin K antagonists (e.g., warfarin, rivaroxaban) because supplementation can attenuate anticoagulant efficacy; dose adjustments should be managed by a healthcare professional.
Caution is advised for individuals with cholestatic liver disease, as impaired bile flow may impair absorption.
Infants receiving high-dose vitamin K1 (e.g., for prophylaxis) should be monitored for hyperbilirubinemia, but routine adult supplementation does not pose significant risk.

Vitamin K1 (phylloquinone) has the molecular formula C₃₁H₄₆O₂ and a molecular weight of 450.7 g/mol.
Its IUPAC name is (2E,4E,6E,8E,10E,12E,14E,16E)-2‑[3‑(4‑hydroxy‑3‑methoxyphenyl)propyl]‑3,7,11,15‑tetramethyl-2,4,6,8,10,12,14,16‑octaheptadienyl‑1‑hydroquinone.
The structure consists of a 2-methyl-1,4-naphthoquinone core with a phytyl side chain (a 20-carbon saturated hydrocarbon) attached at the C-3 position, and a 4-hydroxy-3-methoxy-phenyl group at C-2.
The quinone ring confers redox activity essential for the vitamin K cycle.
The long lipophilic side chain facilitates membrane integration and transport via lipoproteins.
Phylloquinone is lipophilic, poorly soluble in water, but readily soluble in organic solvents like ethanol, chloroform, and in oil-in-water emulsions used in supplements.

Natural vitamin K1 is predominantly derived from green leafy vegetables (spinach, kale, collard greens) and certain vegetable oils (soy, canola).
Commercially, phylloquinone is extracted from plant sources via solvent extraction followed by purification through chromatography.
An alternative, high-purity synthetic route involves condensation of a quinone core with a phytol side-chain under controlled conditions, yielding a product chemically identical to plant-derived phylloquinone.
Quality-focused manufacturers employ HPLC and LC-MS validation to confirm ≥95 % purity, absence of heavy metals, and consistent vitamin activity.
For supplements, micronized or emulsified formulations improve bioavailability.
Manufacturers should provide batch-specific certificates of analysis and adhere to GMP (Good Manufacturing Practice) to ensure consistency and safety.