#21

It would be if we had some simple way to measure mitophagy or MMP or ATP production, but we don’t. So if vitamin K2 were to increase or decrease ATP production in some tissues by a modest amount you most likely would have no clue it just did so. The best we could do is probably using some very indirect markers, like in the above study where maximum cardiac output was increased. Of course that’s a problematic marke because various other things could change cardiac output.

#22

You are right that there is a question about how to measure things. I look at issues like how quickly my digestion system is operating (I keep records), what my RHR is, what my HRV is.

Interestingly there is a question as to whether a high MK7 level reduces PSA or ApoB. (which is where this topic started).

To some extent with interventions we need first to try them and measure any changes and then continue taking out the intervention and putting it back in and monitoring whether the same change occurs.

Directly measuring membrane potential, however, is hard.

However, for example, I got an unusually low Sodium serum level last week. My supplementation is consistent. Is that because the kidney cells had more mitochondrial energy. I don’t know. However, I will continue tracking this to see if there is a correlation.

Happily this sort of tracking can be done whilst doing other things.

1 Like
#23

I was rummaging around to find a copy of the article about cardiac output. I did find this which references it, but actually clarifies that the dose was in micrograms rather than milligrams.

Human Studies
Vitamin K2 (MK-7), and other menaquinones, have been investigated in multiple human clinical
studies. In an article on the safety of Vitamin K2 (MK-7), the available evidence on the safety of Vitamin
K2 (MK-7) as dietary supplement ingredient was reviewed (Marles et al., 2017). In this review,
published clinical trials that made no mention of whether adverse events occurred or of any other
aspects of safety were excluded. The following section provides an overview of relevant human
studies where safety was considered.
In a double-blind, randomized, placebo-controlled trial with study in 55 healthy pre-pubertal children,
van Summeren et al. (2009) investigated the effects of 45 mcg of Vitamin K2 (MK-7)/day for eight
weeks on different biomarkers and coagulation-related parameters, including serum levels of MK-7
(van Summeren et al., 2009). The details of study participants were as follows: placebo group
consisted of 27 male children- age 6-10 years, average height 133.8 cm, weight 30.4 kg, and BMI 16.8;
the MK-7 receiving group consisted of 28 male children- age 6-10 years, average height 132.2 cm,
weight 29.2 kg, and BMI 16.6. Bone markers and coagulation parameters remained constant over time
in both the placebo and treatment group. The results of this study suggest that oral administration of
45 mcg MK-7/day to healthy, pre-pubertal children for eight weeks increased serum levels of MK-7
and osteocalcin carboxylation without affecting blood coagulation. Periodically the subjects were
checked for the occurrence of adverse events of treatment and none were reported.
In a randomized controlled trial, McFarlin et al. (2017) investigated the effects of dietary
supplementation of Vitamin K2 (MK-7) on cardiovascular responses to a graded cycle ergometer test.
In this study, aerobically trained young (average age 21 years) males and female athletes (n=26) were
randomly assigned either to a control group that received a rice flour placebo or to an intervention
group that received MK-7. For weeks 1 to 4, participants received 320 mcg MK-7/day; for weeks 5 to
8, they received 160 mcg MK-7/day. MK-7 supplementation was associated with a 12% increase in
maximal cardiac output, with a trend toward an increase in heart-rate AUC. No significant changes
occurred in stroke volume. As regards safety, the investigators stated, “At no time during the study
did any participant report an adverse effect to taking either the supplement or the placebo.” (McFarlin
et al., 2017).
Moller et al. (2016) compared the biological effects of placebo, fermentation-derived Vitamin K2 (MK7) (90 mcg) and 3 doses of synthetic MK-7 (45, 90 and 180 mcg) in a randomized double-blinded
parallel study. In this study, healthy adult subjects (n=43; 20-60 years of age) took one of the
supplements daily for 43 days, and the fraction of carboxylated osteocalcin (OC) was compared
between day 1 and day 43 as a marker for Vitamin K activity. The serum concentrations of carboxylated
OC (cOC) and unOC were increased and reduced, respectively, after daily intake of 180 mcg of
synthetic MK-7 for 43 days, indicating increased Vitamin K activity. In this study, 27 subjects reported
a total of 40 adverse events; 32 of these were judged unlikely to be related to the study supplement.
In two cases, the adverse events were judged possibly to be related to the study supplement: dry
mouth from day 4 to the end of the study (180 mcg synthetic MK-7 group) and diarrhea (fermentationderived MK-7 group). Another case of diarrhea in the fermentation-derived MK-7 group was judged
probably to be due to the study supplement. The investigators concluded that the findings provide
evidence that the tested synthetic form of MK-7 is bioequivalent to fermentation-derived MK-7,
exhibits vitamin K activity and is well tolerated in healthy subjects (Moller et al., 2016).
In a double-blind, placebo-controlled trial, Knapen et al. (2015a) investigated effects of 180 mcg MK7/day supplementation on arterial stiffness. In this study, healthy postmenopausal women (n=244)
received either placebo (n=124) or MK-7 (n=120) for three years. At baseline, desphosphouncarboxylated matrix Gla-protein (dp-ucMGP) was associated with intima-media thickness (IMT),
Diameter, carotid-femoral Pulse Wave Velocity (cfPWV) and with the mean z-scores of acute phase
markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three years of MK7 supplementation, cfPWV and the Stiffness Index-β significantly decreased in the total group,
whereas distension, compliance, distensibility, Young’s Modulus, and the local carotid PWV (cPWV)
improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dpucMGP by 50% compared to placebo, but did not influence the markers for acute phase and
endothelial dysfunction. The investigators concluded that long-term use of MK-7 supplements
improves arterial stiffness in healthy postmenopausal women, especially in women having a high
arterial stiffness. The investigators stated that no side-effects have been reported for the long-term
use of MK-7 (Knapen et al., 2015a).
In another study, Knapen et al. (2015b) investigated the effects of a Vitamin K2 (MK-7)-fortified yogurt
drink (28 mcg MK-7/yogurt drink) on Vitamin K status and markers of vascular health. The yogurt drink
was also fortified with n-3 PUFA, Vitamin D, Vitamin C, Ca and Magnesium to support vascular and/or
general health. In this study, 32 healthy men and 28 postmenopausal women with a mean age of 56
± 5 years received either basic or fortified yogurt drink twice per day for 12 weeks. MK-7 was efficiently
absorbed from the fortified yogurt drink. Levels of circulating MK-7 were significantly increased from
0.28 to 1.94 ng/ml. Accordingly, intake of the fortified yogurt drink improved Vitamin K status, as
measured by significant decreases in uncarboxylated osteocalcin and dp-ucMGP. No effects were seen
on markers of inflammation, endothelial dysfunction and lipid metabolism. No adverse effects were
reported (Knapen et al., 2015b).
In a three year study, Knapen et al. (2013) investigated the effects of low-dose Vitamin K2 (MK-7) on
bone health. In this study, healthy postmenopausal women (n=244) received placebo or MK-7 (180
mcg/day) capsules for three years. In addition to bone mineral density (BMD) and bone mineral
content (BMC), circulating ucOC and cOC were measured (the ucOC/cOC ratio served as marker of
Vitamin K status) at baseline and after 1, 2, and 3 years of treatment. MK-7 intake significantly
improved Vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine
and femoral neck, but not at the total hip. Bone strength was also favourably affected by MK-7. MK-7
significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the
vertebrae. At the end of the study, twelve women in the placebo group and nine women in the MK-7
group had withdrawn from the study. The overall drop-out rate was 8.6%. Few complaints were
reported during the study. The complaints in the placebo group were: hair loss and/or brittle nails
(n=2), hot flashes (n=1), knee pain (n=1), numb sensation in arms and legs, washed-out (n=1), and
weight gain (n=2); and in the MK-7 group: bone pain (n=1), hot flashes (n=1), rash around eyes and
ears (n=1), smelly capsules (n=1), and weight gain (n=1). Five women withdrew due to these
complaints; four women in the placebo group and one in the MK-7 group. Compliance was measured
by capsule counts at the end of every half-year period; the mean compliance for both treatment
groups was 97%. The results of this study suggest that MK-7 is well tolerated (Knapen et al., 2013).
In a randomized, double-blind, placebo-controlled trial, Dalmeijer et al. (2012) investigated the effects
of Vitamin K2 (MK-7) supplementation on carboxylation of matrix Gla-protein (MGP). In this study, 60
subjects (age 40-65 years) received supplementation of 180, 360 mcg/day of MK-7 or placebo for 12
weeks. At the end of 12 weeks, a significant and dose-dependent decrease in desphosphouncarboxylated MGP (Dp-ucMGP) was noted groups treated with 180 μg and 360 μg MK-7 (31% and
46%, respectively), while dp-ucMGP levels remained unchanged after placebo treatment. The
osteocalcin ratio also decreased significantly after 12-week supplementation with 180 mcg (60%) and
360 mcg (74%) MK-7, while levels remained unchanged after placebo treatment. These results indicate
improved vitamin K levels and good compliance to the study treatment. Changes over time of dp-
cMGP and t-ucMGP levels did not differ between treatment arms. Other cardiovascular risk factors
did not differ between treatments arms. No adverse effects were reported (Dalmeijer et al., 2012).
Theuwissen et al. (2013) carried out a dose-escalation study to measure the antidotal potency of lower
doses (10, 20 and 45 mcg/day) of Vitamin K2 (MK-7) supplements in healthy volunteers stabilized on
acenocoumarol, a VKA therapy. In addition to conventional INR measurements, response on thrombin
generation and the γ-carboxylation status of specific Gla-proteins with coagulation and
noncoagulation functions were monitored. In this study, 18 healthy men and women (age 18-45 years)
were anticoagulated for four weeks with acenocoumarol; of these 15 subjects attained a target INR of
2.0. In the six successive weeks, subjects were supplemented with increasing doses of MK-7 (10, 20,
45 mcg/day) while continuing acenocoumarol treatment at established individual doses. Apart from
the INR, acenocoumarol treatment significantly increased under-carboxylated forms of prothrombin
(ucFII), osteocalcin (ucOC) and matrix Gla-protein (dp-ucMGP), and decreased endogenous thrombin
generation (ETP). A daily intake of 45 mcg MK-7 significantly decreased the group mean values of both
the INR and ucFII by about 40%. Daily intakes of 10 and 20 mcg MK-7 were independently judged by
two hematologists to cause a clinically relevant lowering of the INR in at least 40% and 60% of subjects
respectively, and to significantly increase ETP by ~20 and ~30%, respectively. Circulating ucOC and dpucMGP were not affected by MK-7 intake. The investigators concluded that MK-7 supplementation at
doses as low as 10 mcg (lower than commonly recommended dose of 45 mcg) significantly influenced
anticoagulation sensitivity in some individuals. Hence, the investigators recommended avoiding use
of MK-7 supplements in patients on VKA therapy (Theuwissen et al., 2013).
Theuwissen et al. (2012) investigated the dose-response effects of extra intake of Vitamin K2 (MK-7)
on the carboxylation of extra-hepatic vitamin K-dependent proteins in a double-blind, randomized,
controlled trial. In this study, a total of 42 healthy adult men and women (age 18 to 45 years) were
randomized into seven groups to receive: placebo capsules or MK-7 capsules at a dose of 10, 20, 45,
90, 180 or 360 mcg/day for 3 months. Circulating ucOC, OC and desphospho-uncarboxylated MGP
(ucMGP) were measured. As the study was conducted with few participants, in order to increase the
statistical power, the researchers collapsed the treatment groups into three dosage groups: placebo,
low-dose supplementation (doses below RDA), and high-dose supplementation (doses around RDA).
The results of this study showed that MK-7 supplementation at relatively low doses in the order of the
RDA increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin
generation (blood clotting) were observed (Theuwissen et al., 2012).
In a double-blind, randomized, placebo-controlled trial, Emaus et al. (2010) investigated the effects of
Vitamin K2 (MK-7) supplementation on bone mineral density in healthy postmenopausal Norwegian
women. In this study, 344 healthy women (ages- 50 to 60 years, 1-5 years after menopause) were
recruited and randomly assigned into two groups, one receiving 360 mcg MK-7 in the form of Nattoderived MK-7 capsules (treatment group- age: 54.7±2.5; weight: 67.5±9.0) and the other with placebo
(age: 54.2±2.5 weight: 67.5±9.8) capsules containing olive oil. The subjects were treated daily for 12
months. In the treatment and placebo group, 131 and 133 subjects completed the study, respectively.
At baseline and 12 months after supplementation, BMD was measured at total hip, femoral neck,
lumbar spine and total body together with serum levels of bone-specific alkaline phosphatase,
Crosslaps, total osteocalcin, cOC and ucOC. No statistical differences in bone loss rates between the
groups at the total hip or any other measurement site were noted at the end of 12 months. Serum
levels of cOC increased and ucOC decreased in the treatment versus the placebo group. No treatment
related significant adverse effects of MK-7 were noted. The results of this study suggest that daily
ingestion of 360 mcg MK-7/day for one year is safe (Emaus et al., 2012)

None of the above have over 0.5mg per day. There is a table I cannot copy which included 2mg once.

Additional Human Studies
Novozymes A/S have conducted additional human clinical trials with Vitamin K2 (MK-7) in subjects at
nutritional risk and/or specific medical conditions.
Study 1
A preliminary open labeled observational study conducted showed that daily oral dose of 100 mcg of
Vitamin K2 (MK-7) for 3 months was associated with a reduction in the frequency, intensity, and
duration of idiopathic muscle cramps (Mehta et al, 2010). This study was conducted on 21 patients
aged 18 to 81 of both sexes. Administration of Vitamin K2 (MK-7) was found to be well tolerated and
there were no reports of adverse events.
Study 2
A study was conducted on 30 patients to evaluate the effects and tolerability of administration of
Vitamin K2 (MK-7) for two months in patients with Peripheral Neuropathy (PN) due to vitamin B12
deficiency and/or diabetes mellitus (Kulkarni et al., 2013). Vitamin K2 capsules of 100 mcg each were
given to these 30 patients twice a day for two months. Administration of Vitamin K2 (MK-7) was found
to be well tolerated and there were no adverse events were reported during the period of therapy.
Study 3
An open labeled study of Vitamin K2 (MK-7) was conducted in 100 patients with Peripheral
Neuropathy (PN) suffering from either Vitamin B12 deficiency and/or diabetes mellitus (Mehta et al.,
2018). Subjects were administered 200 mcg of Vitamin K2 orally for 8 weeks and the patients were
followed for an additional 4 weeks. Administration of Vitamin K2 (MK-7) was found to be well
tolerated and there were no adverse events were reported during the period of therapy.
Study 4
A double-blind, placebo-controlled trial was conducted in 60 patients presenting with Peripheral
Neuropathy (PN) suffering from either vitamin B12 deficiency and/or diabetes mellitus (Vladimir et al,
2021). The subjects were administered either 200 mcg of Vitamin K2 (MK-7) or placebo control for 8
weeks, and then followed for an additional 4 weeks. Administration of Vitamin K2 (MK-7) was found
to be well tolerated and there were no adverse events were reported during the period of therapy.
Study 6
A double-blind, placebo-controlled was conducted in patients with Peripheral Neuropathy (PN)
suffering from either Vitamin B12 deficiency and/or diabetes mellitus with diabetes mellitus (Mehta
et al., 2021). In this study, 20 patients were administered either 200 mcg of Vitamin K2 (MK-7) capsules
or a placebo control orally for 8 weeks and the patients were followed up to 12 weeks. Circulating
levels of Vitamin K2 were also measured in this study, and results showed that administration of
Vitamin K2 resulted in increased circulating levels of Vitamin K2 by the 4th and 8th week.
Study 7
In an Observational study (case series) in 17 Multiple Myeloma patients (age; 18-65 years) having
drug-induced (caused by chemotherapy) Peripheral Neuropathy, showed significant relief in the
symptoms of peripheral neuropathy after daily administration of Vitamin K2-7 capsules (Bhave et al,
2019).
Recently published Human Studies
In a Randomized Controlled Trial by Nahid (Karamzad et al 2020), it was shown that Vitamin K2-7
supplementation seems to be effective in the improvement of glycemic indices, but not the lipid
profile of patients with type 2 diabetes mellitus. In another study by Nahid Karamzad et al (2022), it
was observed that Vitamin K2-7 supplementation can be effective in improving PIVKAII levels, of
patients with type 2 diabetes mellitus. Habitual natto (particularly rich in Vitamin K2-7) intake is
associated with a reduced risk of osteoporotic fractures independent of confounding factors, including
bone mineral density, in Japanese postmenopausal women (Kojima A et al 2020). In a one year
followup randomized trial, oral administration of vitamin K2-7 in patients on haemodialysis patients
reduced serum uc-MGP levels (Oikonomaki T et al 2019). MGP (Matrix Gla Proteins) are one of the
most potent inhibitors of vascular calcification. In a randomized controlled trial on pediatric patients
on regular hemodialysis, it was observed that Vitamin K2-7 and native vitamin D showed a beneficial
effect on calcification regulators (Radwa B, 2022). In a randomized controlled trial (Rahimi Sakak F et
al 2020) in individuals with type 2 diabetes, daily intake of Vitamin K2-7 360 mcg for 12-weeks reduces
fasting plasma glucose (p-adjusted = 0.031) and glycated hemoglobin (p-adjusted = 0.004). in a 3-year
randomized, placebo-controlled clinical trial in postmenopausal women with osteopenia, treatment
of Vitamin K2-7 375 mcg daily as an add-on to calcium and vitamin D increased carboxylation of
osteocalcin. Vitamin K2-7 acts as a cofactor in the carboxylation of osteocalcin (OC) and carboxylated
OC promotes mineralization of bone (Rønn SH et al, 2020). In another randomized placebo-controlled
trial by Rønn SH et al (2021), in postmenopausal women who received Vitamin K2-7 375 mcg daily or
placebo, as an add-on to calcium and vitamin D for 12 months decreased uncarboxylated osteocalcin
and increased p-adiponectin but there was no change in insulin sensitivity. In a prospective cohort
study in children with acute lymphoblastic leukemia, an early beneficial effect of the combination of
Vitamin K2-7 and vitamin D3 on BMD in all patients especially during the period of intensive steroid

In summary, Vitamin K2 (MK-7) has been extensively investigated in over 25 clinical trials, with over
2000 participants. Several of these trials were double-blind, placebo-controlled that are the most
likely to capture any adverse effects in order to support the safety of MK-7 in a diverse population.
Human clinical studies in which MK-7 was administered up to 180 mcg/day for 3 years, or up to 360
mcg/day for 12 weeks, or up to 1080 mcg thrice weekly for 8 weeks did not reveal any significant
adverse effects compared with placebo. Adverse effects specifically attributed to MK-7 were limited
to gastrointestinal upset associated with the product’s smell. The available information from multiple
clinical trials suggest that MK-7 is unlikely to cause any adverse effects in human subjects.

3 Likes
#24

The reference to the study says 320 / 160 mcg, but the actual article written by the authors says 300 / 150 mg. “For weeks 1 to 4, participants received 300 mg/d; for weeks 5 to 8, they received 150 mg/d”. So it seems it is that huge dose.

That the 320/160 mcg dose, not much more than normal supplementation, would cause maximal cardiac output to increase by 12 % seems unbelievable.

Oral Consumption of Vitamin K^ sub 2^ for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise

Andrea L Henning

Alternative Therapies in Health and Medicine 23 (4), 26, 2017

Vitamin K 1 and K 2 are not typically common in a Western diet because they are found in a variety of fermented foods. Vitamin K 2 in particular has been demonstrated to restore mitochondrial function and has a key role in production of mitochondrial adenosine triphosphate. Thus, it is reasonable to speculate that dietary supplementation with vitamin K 2 could increase the function of muscle with high mitochondrial content (ie, skeletal and cardiac muscle). The purpose of this study was to determine if 8 wk of dietary supplementation with Vitamin K 2 could alter cardiovascular responses to a graded cycle ergometer test. The study was a randomized controlled trial. The study took place in the Applied Physiology Laboratory of the Department of Biological Sciences at the University of North Texas (Denton, TX, USA). Participants were aerobically trained males and female athletes (N= 26). Participants were randomly assigned either to a control group that received a rice flour placebo or to an intervention group that received vitamin K 2. For weeks 1 to 4, participants received 300 mg/d; for weeks 5 to 8, they received 150 mg/d. Subjects assigned to the control group received similar doses to mirror the intervention group. Subjects consumed the supplements during an 8-wk period while they maintained their typical exercise habits. At baseline and postintervention, participants completed a standard, graded exercise test on an electronically braked cycle ergometer. Before the test, participants were fitted with a mouth piece, and their oxygen consumption, carbon dioxide production, respiratory rate, and respiratory exchange ratio were measured. In addition, participants were fitted with skin-mounted electrodes that measured noninvasive cardiac output, stroke volume, and heart rate. To assess the cumulative exercise change, an area-under-the-curve (AUC) value was calculated separately for each outcome variable at each treatment time point. Vitamin K 2 supplementation was associated with a 12% increase in maximal cardiac output, with P=. 031, with a trend toward an increase in heart-rate AUC, with P=. 070. No significant changes occurred in stroke volume. Although vitamin K 2 supplementation has previously been reported to improve cardiovascular function in diseased patients, to the research team’s knowledge, the current study is the first to report its potential in active individuals. More research is needed to fully evaluate the potential effects of the observed effects

#25

I think the people writing the submission checked with the authors.

The difficulty here is that of how much time it takes to check with the authors. The web pages for the journal don’t work (I have tried). You can get access to the first page.

The dose quoted in the paper is a huge dose something like 1,000 times the doses in all the other test.

Its difficult to come to a conclusion.

In the end I am inclined to conclude
a) That MK7 does enhance mitochondrial efficiency
b) That no-one has tested the really large doses over say 2mg and reported on them.

I think that is the safer conclusion as it means approaching doses of around 0.3g should be done with caution.

#26

This is a 2011 patent, but fwiw: Dynamic balancing of autonomic nervous system through vitamin mk-7

Inventors of current invention observed serendipitously that vitamin MK-7 can restore the sympathovagal balance and also have cardio protective effect by shortening of QT interval and prolongation of RR interval.
During the study of the pharmacological activity and tolerability of vitamin MK-7, on ANS in Healthy volunteers, Inventors discovered that dysfunction of ANS if present was getting harmonized.
Subjects who have Blood pressure beyond the range of 140/90 (supine) and 100/70 (standing) mm Hg, and Sugar Fasting more than 250 mg% and with any major illness are ruled out of study. All subjects were checked for baseline parameters on 0 day. Vitamin K2-7 (MK-7) in dose of 350 μg was administered on 3ld day after the baseline reading. MK-7 was continued for 2 months. Readings were taken on 3rd day, 15th day, 28st day, 50th day, 56th day and at 62nd day. It was observed that after 2 months of therapy with MK-7, there was a marked normalization in the sympathetic activity which was initially elevated, with little effect on parasympathetic activity (Figure 3 and 4). Other parameters remained unaffected.

#27

Just published: Rhodoquinone carries electrons in the mammalian electron transport chain 2025

Hypoxia and K2 MK7 get a mention @John_Hemming:

Ubiquinone (UQ), the only known electron carrier in the mammalian electron transport chain (ETC), preferentially delivers electrons to the terminal electron acceptor oxygen (O2). In hypoxia, ubiquinol (UQH2) diverts these electrons onto fumarate instead. Here, we identify rhodoquinone (RQ), an electron carrier detected in mitochondria purified from certain mouse and human tissues that preferentially delivers electrons to fumarate through the reversal of succinate dehydrogenase, independent of environmental O2 levels. The RQ/fumarate ETC is strictly present in vivo and is undetectable in cultured mammalian cells. Using genetic and pharmacologic tools that reprogram the ETC from the UQ/O2 to the RQ/fumarate pathway, we establish that these distinct ETCs support unique programs of mitochondrial function and that RQ confers protection upon hypoxia exposure in vitro and in vivo. Ubiquinone (UQ), the only known electron carrier in the mammalian electron transport chain (ETC), preferentially delivers electrons to the terminal electron acceptor oxygen (O2). In hypoxia, ubiquinol (UQH2) diverts these electrons onto fumarate instead. Here, we identify rhodoquinone (RQ), an electron carrier detected in mitochondria purified from certain mouse and human tissues that preferentially delivers electrons to fumarate through the reversal of succinate dehydrogenase, independent of environmental O2 levels. The RQ/fumarate ETC is strictly present in vivo and is undetectable in cultured mammalian cells. Using genetic and pharmacologic tools that reprogram the ETC from the UQ/O2 to the RQ/fumarate pathway, we establish that these distinct ETCs support unique programs of mitochondrial function and that RQ confers protection upon hypoxia exposure in vitro and in vivo. Thus, in discovering the presence of RQ in mammals, we unveil a tractable therapeutic strategy that exploits flexibility in the ETC to ameliorate hypoxia-related conditions.

For example, as the brain experiences intermittent periods of hypoxia, utilization of the RQ-directed ETC may mitigate damage that could be caused by fluctuating O2 levels. The UQ-directed ETC may be favored in tissues such as the heart and skeletal muscle, which rely on high levels of ATP to sustain cycles of contraction and relaxation.
Our discovery of RQ in certain mammalian tissues inspired the development of genetic and pharmacologic tools that reprogram electron flow to the RQ/fumarate ETC in vitro and in vivo. Using these tools, we found that reprogramming the ETC via RQ or its mimetics mitigates hypoxia-induced mitochondrial turnover, metabolic stress, and oxidative stress. Interestingly, exogenous supplementation of vitamin K2 (menaquinone) has been shown to mitigate mitochondrial dysfunction and minimize Aβ42-induced neurotoxicity in flies. Whether these effects are caused by vitamin K2-induced and SDH-mediated fumarate reduction is not yet known. Collectively, these data point to the potential for future development of other synthetic electron carriers that can similarly divert electron flow in the ETC to treat mammalian diseases caused by hypoxia or ETC dysfunction, including mitochondrial myopathies, cancer, diabetes, obesity, pulmonary disease, and sickle cell anemia.
Eukaryotes such as snails; mussels; oysters; and nematodes, parasitic helminths, protists, and bacteria possess the electron carriers menaquinone (MQ) and rhodoquinone (RQ). MQ and RQ have a lower E° than fumarate, allowing electron transfer to fumarate in the ETC.21 UQ is the only known mammalian electron carrier and has a standard reduction potential of +100 mV31 (Figure 1C). Previous attempts to identify alternative electron carriers in mammals have been largely restricted to the heart. Moreover, studies on mammalian tissues have mainly analyzed electron carriers in their oxidized form, limiting detection, especially if the reduced form dominates. Finally, approaches to measure other electron carriers were often done using HPLC-UV-vis, which is less sensitive than current mass spectrometry technologies.
To determine if mammalian mitochondria possess other electron carriers, mitochondria were isolated from mouse tissues, quinones were extracted in a manner that stabilizes their reduced form, and samples were analyzed on liquid chromatography-mass spectrometry (LC-MS). Electron carriers possess a quinone head and a poly-isoprene tail. Quinones with six isoprene units or more are hydrophobic enough to embed in the inner membrane. As expected, UQ with a 9 isoprene unit tail (UQ9) and its reduced form, ubiquinol-9, were detected in all tissues (Figures 1D and S1D–S1J). Peaks that corresponded to the m/z for RQ with 9 isoprene units (RQ9) and its reduced form, rhodoquinol-9, were also detected (Figures 1D–1L, S1D–S1J, and S2G). The major and minor isoprene tail lengths for both UQ and RQ are 9 and 10, respectively (Figure S2G). UQ8 is also detectable, whereas RQ8 was below the detection limit or not present (Figure S2G). There were no detectable peaks that corresponded to the mass-to-charge ratio (m/z) of MQ and menaquinol with up to 10 isoprene units (Figure S2G).

1 Like
#28

That’s interesting. That, of course, is MK7 through to MK13. Only MK7 and MK9 can be bought as supplements, but the others are available in food.

It, of course, explains the difference between MK4 and MK7 when it comes to mitochondrial processing.

I have spent a bit of today reading up on the difference between ETC proteins with mitochondrial DNA and those with nuclear DNA. Interestingly there are hydrophobic proteins in the ETC both from mtDNA and nucDNA. The reason that is important is that it is difficult to transport those proteins to the ETC, but it must imply that the nucDNA ETC hydrophobic proteins are ones which if they are mutated cause serious problems with the ETC. Otherwise there would be a good reason to retain them in the mtDNA.

Coming back to MK7. It does something. That is obvious. I am not sure it is limited to fumarate, but in many ways that does not matter as the key is making mitochondria work better.

#29

I do the fermented natto soybeans every morning. There’s a Korean store nearby that sells it for cheap. It’s massively expensive online unless you just buy the powder (which I’m not sure has the same effect or not).

1 Like
#30

It depends on the dose you are using. I have ordered some powder to enable higher dosing.

#31

The beauty of eating natto is that it alters your gut microbiome to be more mk7 productive. I’ll try to to dig out the research. So it has an enduring benefit

2 Likes
#32

Hi John,
The most effective method of improving mitochondrial function is NTFactor Lipids…it repairs and replaces damaged cellular and mitochondrial membranes throughout the body…which results in significant increases in ATP energy production. For more information about revolutionary life extension product email me at: rosspelton70@gmail.com

#33

Better than exercise?

3 Likes
#34

I am mildly sceptical about this. If you have good evidence for these claims please post them in the forum.

3 Likes
#35

I’ll just leave this here

4 Likes
#36

The conclusion is that NTFactor Lipids is total bullshit, correct?

5 Likes
#37

I haven’t seen clear evidence that it’s uniquely helpful (or helpful at all) beyond supplementation of similar lipids (soy lecithin, phosphatidylcholine, etc.). I should caveat that by saying I view case studies in tiny journals to be equivalent to forum experience posts. So, yes, this is definitely in the “probably not harmful, if you want to try it to see if it subjectively helps, go for it.” Their huge list of studies is at best clever marketing, and at worst bullshit (although arguably these are the same thing).

I’m happy to change my mind on this if @DrRoss or someone else would like to point to a specific study from their list that provides better evidence than a case study and uses NTFactor Lipids specifically (and not the multivitamin + NTFactor Lipids formulation).

3 Likes
#38

HI,
For those of you who want to learn more about NTFactor Lipids; it contains healthy, non-oxidized phospholipids that the body utilizes to repair cellular & mitochondrial membranes throughout the body. In scientific publications, studies with NTFactor Lipids is referred to as Membrane Lipid Replacement (MLR). Improvements in mitochondrial function with NTFactor Lipids are documented by using the Rhodamine fluorescent dye. Damaged mito membranes are not able to uptake Rhodamine dye, however healthy mito membranes take up the dye…and this can be visually observed by measuring the level of fluorescence in mito membranes. People taking NTFactor Lipids for 1 to 2 months gain significant improvement in mitochondrial membrane function. Studies in patients with fibromyalgia and chronic fatigue have documented decline in fatigue & improvements in energy.

The best study to read which reviews benefits from NTFactor Lipids is the study done with Gulf War Veterans who experienced wide-ranging health problems due to exposure to chemical, environmental and biological toxins during their tour(s) of duty. Here is the link to that study:
chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://ntfactor.com/wp-content/uploads/2022/06/59-Nicolson-et-al.-Memb.Lipid_.Replacem.Veterans.Study-Nicolson-IJTM-2022.pdf

The peer-reviewed journal Nature Cell Science recently published an extensive review article by Nicolson, et al. itled: Membrane Lipid Replacement and its Use in Restoring Mitochondrial Membrane Function and Reducing Various Symptoms in Aging and Aged-Related Clinical Conditions Here is the link to that publication:
chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://cellnatsci.com/wp-content/uploads/2025/01/10-61474-ncs-2024-00038.pdf

Feel free to contact me for more information regarding NTFactor Lipids.

Healthy regards, Ross rosspelton70@gmail.com

1 Like
#39

Hi Joseph,
Exercise stimulates the body to build new/more mitochondria…but it doesn’t effectively repair damaged mitochondrial membranes. Therapy with NTFactor Lipids is an autophagy-like mechanism. When autophagy is activated, damaged proteins and enzymes are broken down, and the component amino acids are used to build healthy new proteins and enzymes. However, repair of damaged cellular and mitochondrial membranes doesn’t work this way. Most people do not consume adequate amounts of healthy, non-oxidized phospholipids in their diet. Thus, the body doesn’t have the raw materials it needs to accomplish membrane lipid repair. However, NTFactor Lipids delivers therapeutic doses of healthy phospholipids, which the body then utilizes to accelerate membrane lipid repair. People feel the improvements…and it is scientifically measurable and documented. Repair and renewal of cellular and mitochondrial membranes with NTFactor Lipids is an important advancement in life extension and slowing down the process of biological aging.

1 Like
#40

Thanks @DrRoss. This is certainly more compelling evidence than the studies I looked at as it moves up the evidence hierarchy slightly above a single case study (open label w/ 20 participants). I would still be cautious about changing my statement of “probably not helpful, not harmful”. Perhaps “If suffering from gulf war illness, possibly helpful, otherwise probably not helpful and not harmful.” I wouldn’t be opposed to extending this beyond GWI to possibly helpful for people with very very high environmental toxin load (past or present).

I’d still prefer to use soy lecithin because it has RCTs showing benefits. It’s not clear to me that NTFactor Lipids is uniquely beneficial. Perhaps in GWI the same result would have occurred with soy lecithin.

3 Likes