Vitamin K2 in cancer treatment

Vitamin K2: Anticancer Research & Clinical Evidence

Exploring the therapeutic potential of menaquinone in cancer treatment and prevention

Summary

• Apoptosis Induction: Vitamin K2 triggers programmed cell death through multiple pathways
• Cell Cycle Arrest: Prevents cancer cell proliferation by inhibiting CDK proteins
• Oncogenic Pathway Modulation: Activates p53 tumor suppressor and inhibits Bcl-2, c-Myc
• Clinical Success: 45-90 mg/day reduces HCC recurrence by 20-30% in trials

What is Vitamin K2 (Menaquinone)?

Vitamin K2, also known as menaquinone (particularly MK-4 and MK-7), is a fat-soluble vitamin primarily known for blood clotting and bone health. However, emerging research reveals significant anticancer properties distinct from vitamin K1. Studies demonstrate that Vitamin K2 can inhibit cancer cell growth, induce apoptosis, promote cell cycle arrest, and enhance conventional therapy efficacy.

Mechanisms of Action

Vitamin K2 operates through both canonical (γ-carboxylation-dependent) and non-canonical pathways. It activates tumor suppressor p53, inhibits oncogenic proteins like Bcl-2 and c-Myc, and modulates the Wnt/β-catenin pathway involved in cell proliferation and survival.

Anticancer Mechanisms

Mechanism	Key Pathways/Targets	Cancer Types	Evidence Level
Apoptosis	ROS generation, caspase-3 activation	HCC, bladder, leukemia	Preclinical (in vitro/in vivo)
Cell Cycle Arrest	CDK inhibition, NF-κB downregulation	Gastric, prostate, breast	Preclinical and small trials
Autophagy/Metabolic Stress	AMPK activation, glycolysis upregulation	Bladder, colorectal	Preclinical
Anti-Metastasis	Senescence inhibition, anti-inflammatory	Pancreatic, prostate	Observational and preclinical
Chemosensitization	Synergy with sorafenib, 5-FU	HCC, TNBC, colorectal	Small RCTs and preclinical

Clinical Evidence & Research

Hepatocellular Carcinoma (HCC) Breakthrough

A 2025 RCT found that 45 mg/day MK-4 nearly doubled progression-free survival (from ~6 to 12 months) in HCC patients undergoing TACE treatment.

Combined with sorafenib: Median PFS 7.0 months vs. 2.0 months (P < 0.001)

Observational Studies

Large cohort studies reveal impressive cancer prevention benefits. The EPIC-Heidelberg study found that the highest quartile of Vitamin K2 intake reduced overall cancer mortality by 28%, with particularly strong effects for lung cancer (up to 62% risk reduction) and prostate cancer.

Preclinical Research Highlights

Liver Cancer (HCC)

Binds to HSD17B4, reduces DCP tumor marker, suppresses growth and recurrence in mouse models

Prostate Cancer

2025 study: menadione depletes PI(3)P lipids, causes autophagosome overload and cell death

Bladder Cancer

Induced ROS/JNK/p38-mediated apoptosis, reduced tumor size by 50-70% in xenografts

Dosage & Safety Profile

Therapeutic Dosing Guidelines

• Clinical Trials: 45-90 mg/day MK-4 for HCC (far exceeding dietary needs)
• Starting Dose: Begin with 100 mcg and consult healthcare provider
• Safety: Generally safe up to 45 mg/day for 2 years in studies
• Contraindications: Avoid with warfarin due to clotting risks

Natural Sources & Supplementation

Top Vitamin K2 Sources

#1 Natto

~1000 mcg per 100g (fermented soybeans)

#2 Aged Cheeses

75-120 mcg per 100g (Gouda, Brie)

#3 Egg Yolks

32 mcg per 100g (grass-fed preferred)

Additional sources: Fermented dairy products, organ meats, chicken, and supplements (available as MK-4 or MK-7 forms).

Synergistic Combinations

Research-Supported Combinations

• Vitamin K2 + Vitamin D3: Synergistic effects in triple-negative breast cancer
• K2 + Sorafenib: Enhanced response rates in HCC (50% vs. 25%)
• K2 + 5-FU: Improved chemosensitization in colorectal cancer

Safety Considerations

Vitamin K2 demonstrates excellent safety in clinical trials with minimal side effects. Rare adverse events include nausea or hypercalcemia when combined with high-dose vitamin D.

Important: Monitor liver function in cancer patients and avoid concurrent use with anticoagulant medications without medical supervision.

References & Further Reading

British Journal of Cancer (2025): Vitamin K2 doubles progression-free survival in HCC patients

EPIC-Heidelberg Cohort Study: Vitamin K2 intake reduces cancer mortality by 28% (highest vs. lowest quartile)

Cold Spring Harbor Laboratory (2025): Menadione depletes PI(3)P lipids in prostate cancer cells

Mizuta et al. (2006): 45-90 mg/day MK-4 reduces HCC recurrence by 20-30% in 61 patients

Synergies for Cancer Treatments: Oncogenic signaling pathways and Vitamin K2

Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Vitamin K2 is not FDA-approved for cancer treatment. Always consult with qualified healthcare providers before making significant dietary changes or beginning supplementation, especially during cancer treatment.

Last updated: September 2025