Benefits of vitamin K2 MK4 for the brain and the triage theory
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Benefits of vitamin K2 MK4 for the brain and the triage theory
How do you manage AD – Prevention StrategyForeword
We won't discuss K1 nor really K2 MK7. These 2 forms are active in coagulation (see Chris Masterjohn: "The ultimate vitamin K2 resource"). Indeed, pro-coagulant factors are dependent on vitamin K.
The majority of vitamin K (VK) is primarily produced by microorganisms (bacteria) that synthesize it from food in the intestine. The liver, and to a lesser extent adipose tissue, has the capacity to store VK (reserve): MK1 and MK7 up to MK13, and liver-derived cofactors (as well documented by Schurgers & Vermeer). Thus, no MK4 stored at this level. However, to be intellectually honest, in a deficiency situation, the liver could intensify the conversion of circulating phylloquinone (K1) into menadione, the circulating precursor of tissue-derived MK-4. This is a possibility. But the conversion mechanism would occur in the target tissues themselves (brain, pancreas, testes) via UBIAD1—not directly in the liver. The liver produces the intermediate menadione; the tissues complete the synthesis. In theory, if…
NB: UBIAD1 is an essential enzyme required for MK-4 biosynthesis.
Unfortunately, this is random and inefficient (10 to 15%), and furthermore, increasingly less likely/effective after age 50. One possible route for supplying extrahepatic tissues with vitamin K would be for vitamin K to be repackaged by the liver into LDL, thus constituting a hepatic transport system to peripheral tissues. ScienceDirect (2) Indeed, after intestinal absorption, all forms of vitamin K are incorporated into triglyceride-rich lipoproteins and transported primarily to the liver, but also to other target tissues. Cambridge Core (3)
Regarding MK-4 specifically, this review highlights a crucial point for our argument: the conversion of phylloquinone (K1) to MK-4 occurs in some tissues but not all: MK-4 was most abundant in the brain, kidneys, adipose tissue, and reproductive organs. Conversely, no conversion of phylloquinone to MK-4 was detected in the liver, and no labeled MK-4 was found in the serum. The MK type present in the brain is 90% MK-4.Highlighting the point
Let's reiterate, as this will impact the conclusion at the end of the article: Long-chain MKs (MK-7 to MK-13) have the liver as their primary storage site for MK-7. The liver is therefore not a reservoir for MK-4—rather, it is a site of transit and conversion (K1 → menadione → MK-4 via the UBIAD1 enzyme) before local distribution to target tissues (brain, pancreas, testes, etc.). Thus, there is often actual conversion occurring at the end of the chain. When everything matches well.Feedback missing
The problem is that homeostatic regulation of vitamin K is almost entirely absent compared to other fat-soluble vitamins. Unlike vitamin A or D, there is no known feedback mechanism that signals a peripheral MK-4 deficiency to the liver and triggers a compensatory mobilization to supply the brain. Vitamin K has no specific plasma-binding protein or known regulatory receptor. And what happens in the brain remains a mystery…Reasonable Hypothesis (work hypothesis)
The liver is seen more as a competitor than a donor in situations of MK-4 shortage. This is precisely what the triage theory of McCann & Ames (2009) (1) — Am J Clin Nutr. 2009;90:889–907 — suggests, which postulates that# in the event of insufficient supply, vitamin K is allocated primarily to hepatic coagulation, to the detriment of extrahepatic tissues (bones, vessels, brain). This would therefore be the opposite of a compensatory mobilization: the liver captures what is available for its own needs, leaving peripheral tissues in a silent deficiency. Priority given to coagulation function. Protection of the species (implying the triage theory). -
The Vitamin K Triage Theory: When the Brain Comes Last
The Fundamental Principle
McCann & Ames (2009) proposed an elegant yet unsettling theory. In situations of insufficient vitamin K intake, the body prioritizes its uses according to a principle of immediate survival: coagulation takes precedence over everything else.
This is an implacable evolutionary logic. An animal that cannot clot dies within hours. An animal whose brain ages poorly takes decades to pay the price. Natural selection has therefore hardwired coagulation into priority—and the liver is the guardian of this priority.No biological alarm will be triggered.
In practical terms: if your daily vitamin K intake is just sufficient to maintain normal clotting (25–35 µg), your clotting factors will be fully carboxylated, your PT will be perfect—and your extrahepatic tissues (bones, blood vessels, brain) will be silently deficient.
Vocabulary: PT = Prothrombin Time (a test that assesses some of the blood clotting factors). The ideal range is between 70–100%. No detection if not under 50%.
But even if you regularly eat aged cheese, like Gouda or Brie, or liver once a week, there is little chance that low-grade inflammation or the immune response will leave enough menadiones (assimilated byproduct) to maintain functional homeostasis. No biological alarm will be triggered. Vitamin K has neither a specific plasma-binding protein, nor a regulatory receptor, nor a known feedback signal to the liver. Standard coagulation testing does not detect this peripheral deficiency — it does not even look for it.
Without direct dietary intake (liver, Gouda, natto) or sufficient conversion of K1 to MK-4, tissues with high MK-4 requirements—such as the brain—are structurally undernourished, without a reliable compensatory mechanism.
Note: Vitamin K2 is used/metabolized in inflammation, defense, and activation processes (carboxylation).An Invisible Deficiency for Decades
This is where the triage theory becomes clinically important. The brain is the body's richest tissue in MK-4 — 90% of the brain's vitamin K is in this form. The brain needs it for:
the synthesis of sphingolipids (myelination, neuronal membrane integrity)
the carboxylation of protein S and Gas6 (neuronal survival, clearance of apoptotic bodies)
protection against oxidative stress
However, if the brain is consistently supplied last, from adulthood onward, the deficiency develops gradually and silently — without symptoms for 20 or 30 years. This is precisely the temporal profile of a neurodegenerative disease.Why AD Strikes More after 65 and Not 80
The incidence of Alzheimer's disease (AD) doubles every 5 years after age 65. The peak prevalence is therefore between 65 and 80 years old — it is no coincidence that this time window corresponds precisely to the convergence of several aggravating factors:- K1 → MK-4 conversion declines with age. The enzymatic efficiency of UBIAD1 and tissue conversion capacity gradually decrease from age 50–60, and even more so in the presence of chronic low-grade inflammation — almost universal after age 65.
- The gut microbiota deteriorates. Age-related dysbiosis reduces bacterial production of menaquinones, which should normally supplement exogenous intake.
- Dietary intake of direct MK-4 plummets. Less liver, fewer hard cheeses, a depleted diet, and frequent fat malabsorption in the elderly.
- Triage intensifies. The liver continues to prioritize coagulation—which remains perfectly functional—while the brain's MK-4 deficiency reaches a critical threshold after decades of accumulation.
The brain doesn't suddenly fail at 70 or 80. It gradually declines over the past 40 or 50 years, and the clinical manifestation—Alzheimer's disease—appears when functional reserves are depleted, typically between 65 and 75 years of age for the most common forms.
In summary
Blood clotting is protected because it protects the species in the short term. The brain and pancreas are sacrificed because their failure is slow, silent, and doesn't prevent reproduction. Evolution didn't anticipate modern longevity. No pertinent. The vitamin K triage theory is perhaps one of the most underestimated explanations for pathological aging in the West. -
Sources and References
- Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?
https://doi.org/10.3945/ajcn.2009.27930 Joyce C McCann, Bruce N Ames.
The triage theory posits that some functions are prioritized when some nutrients’ availability is weak or deficient. Critical functional needs are met first in the body. Survival mode protection.
https://www.sciencedirect.com/science/article/abs/pii/S0304416502001472
3.
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/role-of-menaquinones-vitamin-k2-in-human-health/5B9F317B526629D8BA77B6435F1E5509
Excerpt
Adequate intakes of vitamin K range from 55 to 90 μg/d for adult women and 65–120 μg/d for adult men.
4. Schurgers & Vermeer (2002)
Référence complète : Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta. 2002;1570(1):27–32.
DOI: 10.1016/S0304-4165(02)00147-2
C'est l'étude clé sur la question. Les auteurs avaient établi dans des travaux antérieurs que K1 s'accumule préférentiellement dans le foie, tandis que les ménaquinones présentent un profil de distribution plus large dans les tissus. PubMed
La majeure partie des vitamines K [ingérée via l’alimentation ou apportée par un supplément] est d'abord transportée vers le foie. Toutefois, contrairement à K1, les deux ménaquinones étaient également présentes dans les LDL, et MK-4 était même détectable dans les HDL. ScienceDirect
Une voie possible pour l'approvisionnement des tissus extra-hépatiques en vitamine K serait que les vitamines K soient reconditionnées par le foie dans les LDL, constituant ainsi un système de transport hépatique vers les tissus périphériques. ScienceDirect
5. British Journal of Nutrition / Cambridge Core (2013, Beulens, Vermeer et al.)
Référence complète : Beulens JWJ, Booth SL, van den Heuvel EGH, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K2) in human health. Br J Nutr. 2013;110:1357–1368.
DOI: 10.1017/S0007114513001013
Après absorption intestinale, toutes les formes de vitamine K sont incorporées dans les lipoprotéines riches en triglycérides et transportées principalement vers le foie, mais aussi vers d'autres tissus cibles. Cambridge Core - Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?
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Talk with AI (Claude)
How efficient is the intake of a MK4 supplement, (with enough fat, hereby 25 g fat with some MUFAs), when taking 1 mg (1 000 mcg) K2 MK4?
Question of vehicle only? No intermediate change into menadione, I suppose, since there is no digest process. Need a confirmation, whenever there is a target amount limited to 2-3 mg K2 supplement.
Note: 2 takes of 1 mg MK4 at breakfast and midday meal, with 1 000 UI D3 (both at the same time, AKA 2 x 1 000 UI D3). Brain target.AI says (Claude):
Summary:
A moderate amount of D3 and K2 are co-absorbed in the same chylomicron pathway; so simultaneous intake is fine.
Brain target and dose adequacy: 2 mg/day total is a reasonable range for a brain-focused protocol.
Step 1 — Chylomicrons (intestinal phase, 0–4h postprandial)
Step 2 — Chylomicron remnants → liver (4–6h)
Step 3 — VLDL → IDL → LDL (hepatic re-export, hours to days)
A possible route for extra-hepatic tissue supply is that part of the K-vitamins are re-packed into LDL, which forms a major transport system from the liver to peripheral tissues. ScienceDirect This is the key insight for your brain target — the liver processes the chylomicron-delivered MK4 and re-exports it via VLDL, which is then progressively remodeled into IDL and LDL for peripheral tissue delivery.
Agarose gel electrophoresis of lipoprotein fractions after K2 supplementation revealed distinct chylomicron bands and variations in VLDL and HDL mobility, influenced by dietary lipids and VK2 supplementation. Wiley Online Library
