Oncogenic effects in absence of Vitamin K
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Oncogenic effects in absence of Vit K or when antagonist like coumarin is present
After reading one of Haidut’s posts, I thought it would be useful for some readers to take into account that “more is not better” when talking about HD Vit K2 MK4.
Highlights
· Metabolic flexibility is not enhanced by HD Vitamin K2
· More is not better when we aren’t in crisis (fracture or osteoporosis).
· Research suggests 600–1,500 mcg of MK-4 is optimizing protein osteocalcin (Ocn).
· The Osteocalcin Paradox: Ocn isn't just a "glue" for bone; it’s a hormone. If you megadose K2 and carboxylate all your Ocn, you effectively “lock” it into the bone. Few circulating undercarboxylated osteocalcin (ucOC) is left (nearly requisitioned) but we need some to help your body manage blood sugar and maintain high testosterone levels.Vocabulary: Carboxylation of osteocalcin
Process that enables the protein to bind calcium and hydroxyapatite in bone matrix.
This carboxylation activates osteocalcin for bone mineralization, while undercarboxylated osteocalcin (ucOC) functions as a hormone regulating glucose metabolism.
Carboxylated osteocalcin is considered the active form for bone formation, while the uncarboxylated form is linked to metabolic regulation, namely glucose and testosterone.The Goal: A "gentle wave" that provides enough K2 to suppress oncogenic PIVKA-II and support liver regeneration (Matrilin-2), while leaving enough "room" for your body’s natural hormonal signaling.
Said on another way: Taking HD Vit K2 MK4 (> 5 000 mcg) won’t change much for the bone matrix, but moreover it’s counterproductive for homeostasis. Try to avoid quinones spikes too if you want to protect the liver and the brain (yo-yo effect due to short half-life).Avoiding over-stimulation
Vit K2 promotes the activity of osteoblasts (bone-forming cells) while inhibiting osteoclasts (cells that break down bone).
Osteocalcin is a metabolic hormone. While we want enough Vitamin K to ensure its functions, over-stimulating its carboxylation via high-dose (HD) K2 can potentially suppress bone resorption too aggressively. Healthy bone requires a balance of formation and breakdown; blocking the "cleaning" phase can lead to brittle bone over time and may interfere with osteocalcin's hormonal roles in glucose metabolism and testosterone synthesis.Protecting the Brain from "Quinone Spikes"
The brain and liver thrive on stability. High-dose MK-4 causes rapid "quinone spikes"—bursts of oxidative potential as the body processes the excess. Unused Vit K, combined to Vit E or Q10 leaves derivatives. (4)
• Quinone Stress: Excess MK-4 creates sharp "quinone spikes," forcing the liver to work harder to clear unused compounds, rather than utilizing them for steady regeneration (via Matrilin-2).
• The Better Way: Small, divided doses (e.g., 1 mg twice daily) create a "gentle wave" of Vitamin K.
• The Result: This provides a constant baseline for brain protection and liver regeneration (via Matrilin-2) without the metabolic stress of clearing out unneeded quinones.Maintaining the cOC/ucOC Balance
The goal of prevention is to reach a ratio of carboxylated (cOC) to undercarboxylated (ucOC) osteocalcin that mimics youthful, healthy levels—not to drive ucOC to zero. Research suggests that doses as low as 600–1,500 mcg of MK-4 are sufficient to optimize this ratio.Practical Takeaway
For long-term prevention, prioritize a low-and-steady intake. Aim for enough K2 to prevent the production of oncogenic PIVKA-II, but not so much that you over-stimulate the system and lose the delicate hormetic benefit of Vitamin K’s natural cycle.Why avoid over-stimulating Osteocalcin?
- Brain & Cell Protection: High doses can cause "quinone spikes," creating unnecessary oxidative stress. A steady, moderate intake (1–2 mg) protects the brain and liver without the "yo-yo" effect.
- Hormonal Harmony: Osteocalcin isn't just for bones; it’s a hormone affecting glucose (5) and testosterone. Over-carboxylating it via megadoses may disrupt the delicate balance between bone formation and natural resorption.
- The Strategy: Use a "gentle wave" approach—low, divided doses that provide constant support for regeneration (via Matrilin-2) without overstimulating the system.
Why the 1 mg MK4 / 1,000 IU D3 Ratio Wins?
"Efficiency is not about the highest dose; it is about the saturability of the system. By combining 1 mg MK-4 with 1,000 IU D3, at the same take, supported by magnesium and choline/inositol, we maximize the carboxylation of bone proteins while sparing the liver's NADPH 'energy pool' and maintaining the endocrine benefits of osteocalcin."You burn Mg and you lack cofactors if you suffer from low-grade inflammation and poor energy metabolism
Taking pharmacological doses (like 45 mg or even 15 mg of MK-4) when not in an emergency (fracture) forces the liver into a "detox" mode. This consumes NADPH and Glutathione, which are better used for systemic repair. 1 mg MK4 is the "sweet spot" for maintenance.
And don't tell me about the Japanese study; I know. We're not talking about bone fracture nor osteoporosis. Only homeostasis, without overload!
=> Warning when taking 400 UI Mix toco, 15 mg / 15 000 mcg MK4, 5 000 UI D3 in 2 or 3 takes / total for a day.
=> It could enhance a "weakening" of the energy pool, when repeated.
Why?
• NADPH Depletion: The reduction of quinones and the action of CYP450 enzymes require NADPH. NADPH is the "currency" used for recycling glutathione and synthesizing fatty acids. If you over-consume it to process 15 mg of MK-4, you have less "antioxidant insurance" elsewhere.
• Glucuronic Acid & ATP: Conjugating metabolites to glucuronide requires UDP-glucuronic acid, a process that consumes glucose and ATP.
• Glutathione (GSH) Risk: If the high-dose quinones undergo "one-electron reduction," they can create semiquinone radicals. Neutralizing these radicals can lead to a direct drain on your Glutathione stores.Sources and References (on my forum)
https://mirzoune-ciboulette.forumactif.org/t2168-english-corner-oncogenic-effects-in-absence-of-vit-k-or-when-antagonist-like-coumarin-is#30606
