Vitamins K1 & K2

Vitamin K1 (phylloquinone, C₃₁H₄₆O₂) & Vitamin K2 (menaquinone-7 C₄₆H₆₄O₂)

Evidence: Strong

Phylloquinone (Vitamin K1) is a fat-soluble vitamin predominantly found in leafy green vegetables. Its primary physiological function is serving as a cofactor for gamma-glutamyl carboxylase, an enzyme critical for the carboxylation of proteins involved in coagulation. This process is essential for proper blood clotting and wound healing, contributing to systemic hemostasis.

Menaquinone-7 (MK-7), a highly bioavailable Vitamin K2 form, is primarily synthesized by gut microbiota or found in fermented foods. It is essential for blood clotting, plays a crucial role in bone strength by activating osteocalcin, and supports cardiovascular health by directing calcium to bones and away from arteries. Additionally, recent reviews suggest its potential role in modulating gut microbiota composition, supporting gut barrier integrity, and influencing inflammation within the gastrointestinal tract, indicating broader gut health relevance.

There are 33,458 peer-reviewed scientific studies on this ingredient.

Selected Study 1/2:

Lai Y, Masatoshi H, Ma Y, Guo Y, Zhang B. Role of Vitamin K in Intestinal Health. Front Immunol. 2022 Jan 5;12:791565. doi: 10.3389/fimmu.2021.791565. PMID: 35069573; PMCID: PMC8769504. 

Study Summary:

Study type: Narrative review in Frontiers in Immunology (2022) that collates animal, cell-culture and limited human data on vitamin K and gut health; no new participants were enrolled.

Observed benefits: Across the literature, vitamin K deficiency is common in inflammatory bowel disease and colorectal-cancer patients, while supplementation or higher dietary intake is associated with reduced gut inflammation, better antioxidant status, improved intestinal-barrier function, more balanced microbiota and, in pre-clinical models, mitigation of colitis and tumour growth.

Mechanisms of action: vitamin K serves as the co-factor for γ-glutamyl carboxylase, enabling vitamin-K-dependent proteins (VKDPs) that modulate coagulation, immunity and epithelial repair; it also shapes microbial composition and their metabolites, suppresses pro-inflammatory cytokines, enhances intestinal alkaline phosphatase and activates AMPK–VDR signalling, together promoting mucosal homeostasis.

Side effects: The review does not report adverse events from vitamin K supplementation; it notes the carboxylation pathway is blocked by warfarin, so high vitamin K intake can interfere with anticoagulant therapy, a well-known caution.

Strength of evidence: Evidence is promising but preliminary. Conclusions rest mainly on mechanistic and animal studies plus small or observational human studies; no large randomized trials yet confirm clinical benefit in intestinal disease. Thus vitamin K appears safe and biologically plausible as gut support, but its therapeutic value still requires robust human RCTs.

Selected Study 2/2:

Aaseth, J. O., Finnes, T. E., Askim, M., & Alexander, J. (2023). The Importance of Vitamin K and the Combination of Vitamins K and D for Calcium Metabolism and Bone Health: A Review. Nutrients, 16(15), 2420. https://doi.org/10.3390/nu16152420

Study Summary:

Study type: Narrative review published in Nutrients (2024) that collates epidemiological studies, 19 randomized controlled trials (RCTs) and several meta-analyses on vitamin K (mainly K2) alone or combined with vitamin D, with no new participants enrolled.

Observed benefits: Observational cohorts (e.g., the 72 000-woman Nurses’ Health Study) link low vitamin K intake to 30 % higher hip-fracture risk; similar associations appear in European and Asian cohorts. Meta-analysis of 16 RCTs in post-menopausal women found K2 supplementation—especially when given with calcium, vitamin D or bisphosphonates—improved lumbar-spine bone-mineral density (BMD) and reduced fractures.

A second meta-analysis of 19 RCTs (6 759 women) confirmed K2 helps maintain vertebral BMD and prevents fractures in osteoporotic women.

Trials combining K2 or K1 with vitamin D3 show additive increases in carboxylated osteocalcin and modest BMD gains, suggesting synergy.

Mechanisms of action:Vitamin K acts as a co-factor for γ-carboxylation of osteocalcin and matrix-Gla protein, enabling these proteins to chelate calcium into bone and keep it out of vessels. MK-4 also binds the steroid-and-xenobiotic receptor, modulating bone-gene transcription. Vitamin D up-regulates osteocalcin synthesis; an adequate K status then activates the protein—explaining the observed K + D synergy.

Side effects: The review reports vitamin K supplements are generally well tolerated; serious adverse events are rare at nutritional doses. Principal caution is interference with vitamin-K-antagonist anticoagulants (e.g., warfarin), so users on such medication should consult a physician. Explicit safety data were scant in the cited trials.

Strength of evidence: Moderate. Consistent biological rationale plus multiple RCTs and two meta-analyses support a benefit of K2—especially alongside vitamin D and calcium—on BMD and fracture risk in post-menopausal osteoporosis. However, many trials are small (<200 participants), heterogeneous in dose (45 mg MK-4 to 180 µg MK-7) and length (6 weeks to 3 years), and some show benefit only when K is added to other therapies. Large, long-term, stand-alone trials are needed to confirm clinical superiority and optimal dosing.