Menaquinone-7 - an interesting molecule to power up the mitochondria

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A preliminary study on the reference intervals of vitamin K in some areas of Beijing with normal physical examination population 2025

The level of serum MK7 showed a significant upward trend with increase of age (P < 0.001).
The findings demonstrated statistically significant differences in serum VK1, MK4, and MK7 levels across the young, middle-aged, and elderly age groups. In contrast, within each age group, no significant disparities were observed between male and female subgroups. Consequently, this study utilised age-based categorization to establish reference intervals for VK1, MK4, and MK7.
The reference intervals for MK7 established in this study, both the lower and upper limits, were significantly lower than the average concentrations reported in Japanese women of different age groups (4.96, 8.42, and 4.21 ng/mL), which is closely related to the widespread consumption of vitamin K-rich natto in Japan. The lower limit of the MK7 reference interval established in this study is lower than the normal adult reference interval reported in Italy (0.33–4.48 ng/mL), with nearly 94% of the detected values below the mean of 0.85 ng/mL reported for women of reproductive age in domestic studies, yet the lower limit of our reference interval is close to the lower bound of the established reference interval of 0.12–3.54 ng/mL.
Therefore, the lower bounds of the reference intervals established in this study, except for MK4, are close to those in domestic and international related studies. The differences in the high values of the upper limits are closely related to individual differences in the study population, as well as regional and dietary nutritional status. This also suggests that different regions and individuals have a relatively consistent tolerance to vitamin K deficiency, but have a higher tolerance for different serum concentrations and high doses of VK.

Why would MK7 increase with age in healthy people?

[John_Hemming]

@adssx

Why would MK7 increase with age in healthy people?

Potentially a variation in diet. Alternatively a change to the pathways that metabolise it. Obviously supplementation is a possiblility.

What would be useful is to know what daily consumption links to which serum concentrations.

[adssx]

@John_Hemming

Obviously supplementation is a possiblility.

No:

Subjects with one of the following conditions or diseases were excluded: use of antibiotics for more than 10 days, digestive system diseases, long-term diarrhoea, liver disease, jaundice, liver dysfunction, pancreatic dysfunction, diabetes, renal dysfunction, family history of bleeding and coagulation related diseases, anaemia, taking oestrogen drugs, taking lipid-lowering or weight loss drugs, recent vitamin supplementation, nervous system diseases, immune system diseases, tumours, abnormal blood pressure, coronary heart disease, atherosclerosis, and dyslipidemia.

@John_Hemming

What would be useful is to know what daily consumption links to which serum concentrations.

According to Medichecks:

[Joseph_Lavelle]

@adssx Gut microbiome changes with age?

[adssx]

Could be. ChatGPT suggests the potential explanations:

• Liver function declining with age (even among healthy individuals) => slower clearance or altered tissue uptake of MK7 => higher circulating levels in older age groups
• “Aging might trigger compensatory mechanisms that affect the distribution, storage, or recycling of MK7, ultimately leading to higher serum levels”
• “Even in healthy populations, the composition of the gut microbiome changes with age. These natural age-related shifts might favor the bacterial species that produce MK7, thereby increasing its endogenous levels in older individuals.”

At the end… is high MK7 good or bad?

Association studies looked at K1 + K2 or all K2 (MKs) but not specifically MK7:

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study

The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively].

Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis 2019

A significant association was found between dietary phylloquinone and total CHD (pooled HR 0.92; 95% CI 0.84, 0.99; I 2 = 0%; four studies), as well as menaquinone and total CHD (0.70; 95% CI 0.53, 0.93; I 2 = 32.1%; two studies). No significant association was observed between dietary vitamin K and all-cause mortality, CVD mortality, or stroke. Elevated plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K deficiency, was associated with an increased risk of all-cause mortality (1.84; 95% CI 1.48, 2.28; I 2 = 16.8%; five studies) and CVD mortality (1.96; 95% CI 1.47, 2.61; I 2 = 0%; two studies).

Vitamin K status and cardiovascular events or mortality: A meta-analysis 2020

Similarly, there were no significant associations of menaquinone for the risk of all-cause mortality (hazard ratio 0.96; 95% CI 0.84–1.09; I 2 = 0.0%, p = 0.707) and CVD mortality (hazard ratio 1.02; 95% CI 0.77–1.35; I 2 = 0.0%, p = 0.644) in a random effects model.

[John_Hemming]

https://www.nature.com/articles/s41598-024-56151-w

[CronosTempi]

Are we sure these cross country measurements are uniform? I’m not so sure. See:

Vitamin K plasma levels determination in human health

Vitamin K plasma levels determination in human health

[adssx]

What’s your point? (this study is briefly cited in the above article btw)

[John_Hemming]

So the serum concentrations were below those you would get from supplementation

[CronosTempi]

Based on the paper I cited, I have no confidence in the numbers from that Chinese study. And especially no confidence in their comparison with other countries with different ways of measuring. And furthermore, I think the rising MK-7 levels in the elderly could very well be a measuring artifact.

[DrRoss]

Hi,
Of course…no way to tell how soy lecithin would compare to NTFactor Lipids in a randomized clinical trial…and of course, no one will fund such a study. But…I don’t believe many people take a therapeutic dose of soy lecithin every day…NTFactor Lipids is concentrated healthy, non-oxidized glycerophospholipids. I’d be interested to read the RCT trials with soy lecithin you refer to. I’m convinced that Membrane Lipid Replacement with NTFactor Lipids is an extremely important and effective life extension supplement/therapy. Ross

[dicarlo2]

Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged...

[DrRoss]

Hi…I read the full text of Hirose, et al study titled Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged women: a randomized, double-blind, placebo-controlled study. The outcomes were assessed using two methods: The Chandler Fatigue Score and the Profile of Mood States (POMS) rating scales. The results stated A) There were no significant differences in the changes in Chalder Fatigue Scale score (placebo vs low-dose vs high-dose groups:…so soy lecithin worked no better than placebo, B) The POMS measures 30 items covering six major domains (tension, depression, anger, vigor, fatigue, and confusion). The results on POMS rating stated soy lecithin lowered diastolic BP and increased vigor…(not really sure what vigor is)…but no mention of improvements in tension, depression, fatigue and confusion.

Here are the improvements in Gulf War Veterans treated with NTFactor Lipids. Within 3 to 6 months, significant improvements in the following 22 symptoms categories: 1) heart, 2) nose/throat, 3)breathing, 4) Neurologic, 5) sleep, 6) fatigue, 7) hair/scalp, 8) skin, 9) urinary, 10) oral cavity, 11)balance, 12) eye/vision, 13) senses, 14) auditory, 15) joints, 16) muscles, 17) allergies, 18)Infections, 19) gastrointestinal, 20) pain, 21) genital, 22) chemical sensitivities.

Participants in numerous studies with NTFactor Lipids (fibromyalgia, chronic fatigue, general population and aged individuals) ALL gain significant reductions in fatigue, whereas in the Hirose, et al study the authors state, “In this study, significant differences in the fatigue scores among the groups could not be shown.” I think NTFactor Lipids is far superior that high dose soy lechtiin.

Individuals who want more information about Membrane Lipid Replacement and NTFactor Lipids contact me at: rosspelton70@gmail.com

[adssx]

@L_H

The beauty of eating natto is that it alters your gut microbiome to be more mk7 productive.

Do you have a source backing this claim?

A few other longitudinal studies on natto (others here):

Impact of dietary habits on renal function in Saku, a rural Japanese town: a cohort study 2024

In total, 3,899 participants were analyzed. The overall prevalence of patients with eGFR < 60 mL/min/1.73 m2 was 11% (n = 434, male; 7.1%, female; 4.1%). The groups with a high intake of chicken (approximately 63.4 g/day, adjusted OR: 0.632, P = 0.003), natto (fermented bean; approximately 21.7 g/day, adjusted OR: 0.679, P = 0.01), and plant protein (approximately 0.8 g/ideal body weight/day, adjusted OR: 0.695, P = 0.042) showed a low risk of developing CKD compared to the group with the lowest intake.

@John_Hemming: per ChatGPT, 21.7 g of natto contains roughly 240 µg of MK-7.

Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children’s Study 2020

Regarding soy foods, intakes of miso soup and natto were inversely associated with GDM incidence (both P for trend ≤ 0.01), whereas the association for tofu intake appeared to be nonlinear (P for trend = 0.74).

Fermented soy products intake and risk of cardiovascular disease and total cancer incidence: The Japan Public Health Center-based Prospective study 2020

In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes.

Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study 2017

The highest quartiles of total soy protein and natto intakes were significantly associated with a decreased risk of mortality from total stroke (HR = 0.75, 95% CI: 0.57, 0.99, P-trend = 0.03 and HR = 0.68, 95% CI: 0.52, 0.88, P-trend = 0.0004, respectively). The highest quartile of natto intake was also significantly associated with a decreased risk of mortality from ischemic stroke (HR = 0.67, 95% CI:0.47, 0.95, P-trend = 0.03).

Per Table 2, the top quartile ate >7.3 g of natto daily so roughly 80 µg of MK-7.

In the dementia paper I posted previously, the top quintile was eating about 26 g of natto daily so about 300 µg of MK7

[L_H]

@adssx

Do you have a source backing this claim?

Good question. It’s been a while since i looked at this, and now in haste, but a quick ai search supported the idea That * Studies have shown that natto can increase the abundance of B. subtilis in the gut.
Fluctuations in Intestinal Microbiota Following Ingestion of Natto Powder Containing Bacillus subtilis var. natto SONOMONO Spores: Considerations Using a Large-Scale Intestinal Microflora Database.

But whether its impact is significant, or not, is an open question: The impact of gut bacteria producing long chain homologs of vitamin K2 on colorectal carcinogenesis - PMC

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Dysregulation of Astrocyte-derived Matrix Gla Protein Impairs Dendritic Spine Development in Pyridoxine-dependent Epilepsy 2025

In spite of adequate seizure control, approximately 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. However, it is still unknown the mechanisms underlying brain dysfunction in PDE patients even when seizure control is achieved. In this study, we show that mice with specific deletion of Aldh7a1 from astrocytes, but not neurons, exhibit pyridoxine-dependent epilepsy, and have defective dendritic spine development and cognitive impairment when seizure occurrence is well controlled. Mechanistically, ALDH7A1 deficiency leads to dysregulation of astrocyte-derived matrix gla protein (MGP), one of vitamin K dependent proteins, thereby impairing dendritic spine development and synaptic transmission. Notably, supplementation of menaquinone-7, a form of vitamin K, promotes MGP activation and rescues defective dendritic spine development, abnormal synaptic transmission and cognitive impairment in Aldh7a1-deficient mice. Therefore, our findings not only unravel the important role of ALDH7A1 in astrocytes contributing to the pathogenesis of PDE, but also provide a potential therapeutic intervention to ameliorate cognitive impairment in PDE beyond pyridoxine treatment.

[adssx]

Effect of Menaquinone-7 (MK-7) Supplementation on Anthropometric Measurements, Glycemic Indices, and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 2025

Iranian paper

• Six randomize clinical trial studies entered to the final analysis.
• MK-7 supplementation has desirable effects on insulin, HbA1c, and HOMA-IR.
• MK-7 intake doesn’t significantly affect anthropometric measures and lipid profile.
  _ MK-7 is more effective when diabetes patients received ≤90 mg.

I guess mg means µg? Low quality paper…

[Nlo]

For some reason that I cannot recall at the moment, I have been ensuring that I take extra MK7 and MK4 on the days that I take rapa. I know that I did it for a presumed benefit, but I see someone suggesting that it might be good to avoid it around rapa days. Can someone explain the rationale to take K2 or avoid around Rapamycin days? Thanks!

[John_Hemming]

Its complicated because the number of isoprene residues has a material effect.