350 replies to this topic

[krillin]

I can't find much on phase I/II ratio. Do you have any references/summary papers that will help me get acquainted with these concepts?

Blue's LPI isothiocyanate link has a good description and some references.

[krillin]

Adverse effects for mk4? As far as I know such bad effects were apparent even in the one and two year long Japanese 45 mg mk4 studies, such as increased risk for skin lesions. There were no adverse effects in the four year ECKO trial. On the contrary, regsrding the adverse effect you are afraid of, cancer, exactly the opposite was seen.

You comparison of the Western and Japansese intake is strange. Obivously you cannot compare the highest western quartile in the Heidelberg with the average intake in young Japense women. Obviously the highest Japanese quartile will be higher than the average value. Further, most likely the not unusual Japanese who eat natto regularly as part of the breakfast will have an mk7 intake monstrously larger than those who do not eat natto. Which makes it important to differentiate natto and not natto eaters in Japan.

Anyway, it seems to me that your are making a classic human cognitive mistake. Which is to assume that best course of action is to do nothing when there are any conflicting data. Which is incorrect, no action is also an action. Lets weight the evidence: a chick embryo liver study and a cancer prone rodents given an intraperitoneal toxin study against a small four year double-blind human trial showing large, blood concentration dependent, reductions in cancer (p = 0.02; HR = 0.25, 95% CI 0.07 to 0.89) and general severe disease. The evidence weighs overwhelmingly in favor of K1. By the way, the same really applies to FDA approval or not. The FDA prefers to have overhelming evidence for no negative effects for political and judicial reasons. But for a patient dying of a disease, the rational course is not to wait and die by waiting many years for the FDA to cover its ass by superexpensive and very long safety studies, but to take a new drug immediately when the risk:reward ratio get largely favorable.

The first MK-4 trial I could find was from 1998. The first report of side effects was 2005. That's 7 years, not 1-2.

If K1 increases cancer risk, its via increasing initiation by carcinogens, and cancer can have latency periods of 20 years. A 4 year trial wouldn't catch that.

You're right, I was too lazy in picking a MK-7 dose. PMID: 18079608 reports that for MK-7, ng/ml = 0.061 (mcg/day from natto) + 2.525. PMID: 16469998 reports that for optimal carboxylation of OC women age 50-69 need MK-7 concentrations of 3.9 ng/ml and age 70+ need 6.4 ng/ml. Which translates into intakes of 22 and 64 mcg/day, respectively. 45 mcg/day is thus a reasonable dose for non-senior citizens.

I'm not dying and I have time to wait for SENS to save us, so inertia is a good thing. The potential amount of damage I could do with K1 seems much greater than the potential incremental benefit of adding it to my MK-7 intake.

[Blue]

I dislike that you made a partial citation of my last post without indicating that much material was removed and never replied to.

Regasrding the Japanese mk4 studies, they all have various large problem, such as many (or all?) being open-label, which makes evaluating of often subjective sife effects nearly impossible and report of adverse effects was poor. Most of the reported side effects are from the supplement/drug manufacturer which has used unclear sourcea. But in one of the studies, a 3 year + 1 year follow-up study, (only reported as a press release by the supplement manufacturer!) we can see more adverse effects. In contrast, the ECKO trial was double-blind and found no adverse effects after four year.
http://www.hta.ac.uk...mm/summ1345.htm
http://www.eisai.co....news200506.html

Not sure if there is a 20 years double-blind study ever done anywhere in the world. New pharmaceutical drugs certainly never test for anything that long.

http://www.jstage.js...53_419/_article
http://www.ajcn.org/...t/full/83/2/380
Thanks for the studies! Some thoughts:
1) Large interlaboratory differences in measuring MK-7 have been suggested as per the second study. So you will likely be in trouble when you try to interpolate blood levels and intake from different studies.
1) The statistical, theoretical calculations in the second study looks dubious. Like that K vitamin blood concentrations have essentially no effect on ucOC:iOC concentrations in those under 50 years old. The paper itself in fact cites two studies showing that 1000 mg K1 is required to maximaize ucOC:iOC in young people and that this gives a blood concentration far, far above that which should be required according to its own theoretical caclculation.

You could be or will be dying from a cancer or severe disease that K1 would have prevented according to ECKO trial. That mk7 will have the same effect as K1 is highly uncertain due its virtual absence in the body outside blood. It may be that mk7 is converted to mk4 in humans and duplicates all beneficial effects of K1 if given in a high enough dose. Or not.

So far you have only presented evidence that K1 is dangerous is you are a caner prone rodent given an interperitoneal injection of benzo(a)pyrene.

Edited by Blue, 23 June 2010 - 08:02 PM.

[stephen_b]

I dislike that you made a partial citation of my last post without indicating that much material was removed and never replied to.

Blue, no need to get so combative. Low in magnesium?

[FunkOdyssey]

That doesn't sound combative to me. Seems like a reasonable statement from Blue.

[krillin]

I dislike that you made a partial citation of my last post without indicating that much material was removed and never replied to.

Why? (Note to readers: I'm doing the very same thing in this post. If you want to read all of Blue's comments that are not germane to my comments, you're going to have to scroll up and read his post.)

1) Large interlaboratory differences in measuring MK-7 have been suggested as per the second study. So you will likely be in trouble when you try to interpolate blood levels and intake from different studies.

Are there any studies on long-chain K2 in which 45 mcg/day will not put a person (under 50 years old) into the most favorable group?

So far you have only presented evidence that K1 is dangerous is you are a caner prone rodent given an interperitoneal injection of benzo(a)pyrene.

And you haven't presented any proof that megadose K1 does not enhance the carcinogenicity of dietary or environmental BP in humans and that MK-7 can not provide all the benefits of the K family.

In the face of uncertainty, it's best to take the sure thing, like using index funds instead of actively-managed funds. MK-7 is the only vitamer that has the effects we want in doses that large populations have taken for decades without any problems.

[Blue]

There are zero controlled trial of mk7. What amount of mk7 that would be equivalent of 1000 mcg k1 is unknown. Particularly for functions outside blood since one cannot assume that whatever value would give an equivalent blood ucOC:iOC ratio also gives similar effects outside blood since mk7 hardly seems to leave the blood.

Sure, mk7 looks good in epidemiological studies, but so did a lot of other things that did not produce a good effect when tested in clinical trials.

I have presented a four study giving 5 mg k1 finding greatly reduced cancer risk in humans. You have not presented a study showing that mk4 or mk7 is not also bad in cancer prone rodents given interperitoneal injection of benzo(a)pyrene. That this is applicable to human metabolism is unproven and even if it is it may be at amounts of k vitamins or benzo(a)pyrene never encountered normally.

Regarding funds, sure it is nicer to have a safe return than a volatile return if the average return is the same. But that is not the situation here. You are claiming that a human, double-blind, four-year long study is as valuable as a study on cancer prone rodents given an interperitoneal injection of one particular toxin (not even having shown that the same does not apply to your own alternative). But that is a common cognitive error, freeze and do nothing when there are conflicting data, however unbalanced in value.

Edited by Blue, 26 June 2010 - 07:03 AM.

[Blue]

You asked for a study showing that 45 mcg mk7 was not optimal. In this study blood values of mk7 both in Japan and Britain were compared. "Serum MK-7 concentrations were 5.26 ± 6.13 ng/mL (mean ± SD) in Japanese women in Tokyo, 1.22 ± 1.85 in Japanese women in Hiroshima, and 0.37 ± 0.20 in British women." Thus mk7 intake seems to be much, much higher especially in certain regions in Japan. Furthermore, the regional difference in Japan in mk7 intake varies with hip fracture incidence. Exactly what this translates into regarding intake is uncertain but seems that an mk7 intake much, much higher than the Western or at least British average intake is beneficial.
http://cat.inist.fr/...N&cpsidt=992923

[krillin]

You asked for a study showing that 45 mcg mk7 was not optimal. In this study blood values of mk7 both in Japan and Britain were compared. "Serum MK-7 concentrations were 5.26 ± 6.13 ng/mL (mean ± SD) in Japanese women in Tokyo, 1.22 ± 1.85 in Japanese women in Hiroshima, and 0.37 ± 0.20 in British women." Thus mk7 intake seems to be much, much higher especially in certain regions in Japan. Furthermore, the regional difference in Japan in mk7 intake varies with hip fracture incidence. Exactly what this translates into regarding intake is uncertain but seems that an mk7 intake much, much higher than the Western or at least British average intake is beneficial.
http://cat.inist.fr/...N&cpsidt=992923

Using the equation I posted earlier, 45 mcg/day should yield a very nice 5.27 ng/ml. The British would get MK-9 in their diet, not MK-7, so their data point isn't very informative.

I'm going to have to withdraw the portion of my objection to K1 that was based on detox effects, since vitamin E does the same thing. Vitamin E has been studied to death and it only gives you cancer if you have a smoker's exposure to BP.

Mol Aspects Med. 2003 Dec;24(6):337-44.
Homologous metabolic and gene activating routes for vitamins E and K.
Landes N, Birringer M, Brigelius-Flohé R.
Department of Vitamins and Atherosclerosis, German Institute of Human Nutrition, University of Potsdam, Arthur-Scheunert-Allee 114-116, Bergholz-Rehbruecke D-14558, Germany.
Abstract

Vitamins E and K share structurally related side chains and are degraded to similar final products. For vitamin E the mechanism has been elucidated as initial omega-hydroxylation and subsequent beta-oxidation. For vitamin K the same mechanism can be suggested analogously. omega-Hydroxylation of vitamin E is catalyzed by cytochrome p450 enzymes, which often are induced by their substrates themselves via the activation of the nuclear receptor PXR. Vitamin E is able to induce CYP3A-forms and to activate a PXR-driven reporter gene. It is shown here that K-type vitamins are also able to activate PXR. A ranking showed that compounds with an unsaturated side chain were most effective, as are tocotrienols and menaquinone-4 (vitamin K(2)), which activated the reporter gene 8-10-fold. Vitamers with a saturated side chain, like tocopherols and phylloquinone were less active (2-5-fold activation). From the fact that CYPs commonly responsible for the elimination of xenobiotics are involved in the metabolism of fat-soluble vitamins and the ability of the vitamins to activate PXR it can be concluded that supranutritional amounts of these vitamins might be considered as foreign.

PMID: 14585304

IUBMB Life. 2002 Aug;54(2):81-4.
Tocotrienols inhibit human glutathione S-transferase P1-1.
van Haaften RI, Haenen GR, Evelo CT, Bast A.
Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, The Netherlands. R.vanHaaften@farmaco.unimaas.nl
Abstract

Tocopherols and tocotrienols are food ingredients that are believed to have a positive effect on health. The most studied property of both groups of compounds is their antioxidant action. Previously, we found that tocopherols and diverse tocopherol derivatives can inhibit the activity of human glutathione S-transferase P1-1 (GST P1-1). In this study we found that GST P1-1 is also inhibited, in a concentration-dependent manner, by alpha- and gamma-tocotrienol. The concentration giving 50% inhibition of GST P1-1 is 1.8 +/- 0.1 microM for alpha-tocotrienol and 0.7 +/- 0.1 microM for gamma-tocotrienol. This inhibition of GST P1-1 is noncompetitive with respect to both substrates CDNB and GSH. We also examined the 3D structure of GST P1-1 for a possible tocopherol/tocotrienol binding site. The enzyme contains a very hydrophobic pit-like structure where the phytyl tail of tocopherols and tocotrienols could fit in. Binding of tocopherol and tocotrienol to this hydrophobic region might lead to bending of the 3D structure. In this way tocopherols and tocotrienols can inhibit the activity of the enzyme; this inhibition can have far-reaching implications for humans.

PMID: 12440523

So that leaves the objection to K1 and MK-4 based on menadione production during intestinal absorption (PMID: 16469140). MK-7 also breaks down into menadione there, but much less is formed because the MK-7 dose is so much lower than that of the other two. There is a review on iHerb's page for LEF's discontinued 10 mg vitamin K product in which it was blamed for elevated bilirubin. That can be caused by hemolysis, which is an acute adverse effect of menadione. Menadione also causes cataracts (PMID: 9192159), which as an effect of chronic toxicity could be caused by levels lower than those required to cause hemolysis. For the record, can you state that you believe that a four year study can determine the risk of cataract after, say, 40 years of megadosing?

Zero controlled trials of MK-7? What about PMIDs: 19450370 and 20177349? There are a lot more in the queue if you would learn a little patience.

If MK-7 hardly leaves the blood, how did it raise bone concentrations of MK-4 in PMID: 10701161?

Taking a dose of MK-7 that has been taken safely for generations and has a high probability of being able to duplicate all of the benefits of megadoses of K1 and MK-4 is not freezing and doing nothing.

[Blue]

Your "equation", as it can be understood, seems to be based on interpolating several studies. Which as stated previously is dubious because a) there seems to be large interlaboratory differences in measuring vitamin K b) the theoretical study you cite regarding optimal values is extremely dubious since it for those less than 55 years old claims that no vitamin K at all in blood is necessary to give extremely good ucOC:iOC values and furthermore its theoretical calculation contradicts the experimental data regarding what K1 doses is necessary to optimize ucOC:iO.

Your current objectiont to a large amount of K1 is now based on that all the Ks convert to menadione. If menadione is harmful the mk7 is better due to the lower amount necessary. As for that menadione is harmful there are lab studies indicating that it can be a proxidant and the rodent study in rodent prone to cataracts.

As for the prooxidant effect that this occurs in humans is not clear. Even if it occurs, it may not significant with K levels achievable in blood. Even if it occurs, this may not necessarily be harmful. ALA, the only substance shown to incrase lifespan in CR animals, may work by being a prooxidant with a short duration which causes a compensatory uppgrading of cell defenses. There is also the point that giving various antioxidants to human have not been beneficial in many large studies.

There are no increased incidence of cataratcs in the study giving 5 mg of K1 for four years or in Japan for the many people who have ingested 45mg mk4 daily! against osteoporosis for long periodds. Can anyone state that there will no be adverse effects after "40 years"? No, but this applies to any substance. Can you state that not taking K1 will not have harmful effects regarding cancer and severe diseases? Again you are considering a rodent study in rodents prone to a particular disease to be the more important than human placebo controlled studes showing large reductions in cancer and severe disease.

Furthermore, there is evidence that menadione is actually beneficial. There are many studies showing anticancer effects of menadione. For example, here is a study showind synergistic effects of menadione and vitamin D on cancer cells and an upregulation of anitoxidant enxymes. Maybe it is menadione rather than K1 itself that caused the beneficial effects seen from K1 when combined with vitamin D in the ECKO trial?
http://www.ncbi.nlm....pubmed/19429426

Or we can look at this patent application claiming that menadione is more effective than the other vitamin K forms against diseases of protein aggregation.
http://www.freepaten...om/7605179.html

As a sidenote, you earlier claimed that vitamin C is shown to prevent cataracts citing one study. I note this study and its introduction regarding several other studies showing no or even promoting effects of the antioxidant vitamin C on cataracts in humans.
http://www.stat.colu...001/vitamin.pdf

Edited by Blue, 11 July 2010 - 12:33 PM.

[FunkOdyssey]

Are you guys still debating vitamin K? I'm going to keep taking my LEF K complex with all pertinent forms, including K1, MK4, and MK7 for now. If either of you guys ever conclusively wins this argument, let me know and I may consider a different supplement.

[krillin]

Your "equation", as it can be understood, seems to be based on interpolating several studies. Which as stated previously is dubious because a) there seems to be large interlaboratory differences in measuring vitamin K b) the theoretical study you cite regarding optimal values is extremely dubious since it for those less than 55 years old claims that no vitamin K at all in blood is necessary to give extremely good ucOC:iOC values and furthermore its theoretical calculation contradicts the experimental data regarding what K1 doses is necessary to optimize ucOC:iO.

The equation is based on one study of 60 people, not several studies, and it is the best way I have found to estimate MK-7 intake in the study you cited in response to my question, "Are there any studies on long-chain K2 in which 45 mcg/day will not put a person (under 50 years old) into the most favorable group?" And why are you still bitching about the optimal value study? It suggests a requirement of 3.9-6.4 ng/ml depending on age. Your reference suggests 5.26 ng/ml as a good target. Looks like agreement to me. Do you have a better equation for determining how to get to that range?

You can't expect the regression curve to be accurate near K1 concentrations of zero, since there can't have been many data points around there. For the people under 50 years old (not 55 as you state) the K1 blood level was 1.52 ± 1.02 ng/ml. It's also unclear to me if they were able to control for effects from MK-7. So the few data points they had near zero for K1 in people under 50 may have had enough MK-7 to stay carboxylated.

The K1 requirements between those two studies aren't as different as you imply. One (PMID: 16469998) says 1.4-2.5 ng/ml, the other (PMID: 12399278) says 1.6-3.5 ng/ml. (In group A of the latter, 1000 mcg/day wasn't that much better than 500 mcg/day, while in group B 500 mcg/day anomalously underperformed, so it's hard to tell how much extra benefit there is to pushing all the way to 3.5 ng/ml.)

There are no increased incidence of cataratcs in the study giving 5 mg of K1 for four years or in Japan for the many people who have ingested 45mg mk4 daily! against osteoporosis for long periodds.

How do you know there wasn't increased incidence of cataract? The K1 study is silent on the subject and a PubMed search for [cataract (MK-4 OR menatetrenone OR menaquinone OR "vitamin K2")] yields no hits. Absence of evidence does not provide evidence of absence.

Can you state that not taking K1 will not have harmful effects regarding cancer and severe diseases? Again you are considering a rodent study in rodents prone to a particular disease to be the more important than human placebo controlled studes showing large reductions in cancer and severe disease.

By not taking K1 I get a normal risk of disease, minus the risk reduction from MK-7. You're going out on a precarious limb by insisting that MK-7 can't substitute for K1 and that K1 megadoses can't have adverse effects.

Aside from the rodent data, we have one report of a 10 mg vitamin K supplement causing acute toxicity via a menadione mechanism. Are you going to be like the people who ridiculed me for taking seriously anecdotal evidence of harm from vitamin D levels above 60 ng/ml and said that they only worry about adverse effects confirmed by randomized double blind clinical trials? They looked very foolish when the study with vitamin D levels vs all-cause mortality came out a short time later.

Furthermore, there is evidence that menadione is actually beneficial. There are many studies showing anticancer effects of menadione. For example, here is a study showind synergistic effects of menadione and vitamin D on cancer cells and an upregulation of anitoxidant enxymes. Maybe it is menadione rather than K1 itself that caused the beneficial effects seen from K1 when combined with vitamin D in the ECKO trial?
http://www.ncbi.nlm....pubmed/19429426

Or we can look at this patent application claiming that menadione is more effective than the other vitamin K forms against diseases of protein aggregation.
http://www.freepaten...om/7605179.html

These are silly arguments and not up to your usual standard. Menadione is for chemotherapy, not chemoprevention. And for prevention of tau aggregation by menadione, the B50 is a ridiculous 2.78 microM!

As a sidenote, you earlier claimed that vitamin C is shown to prevent cataracts citing one study. I note this study and its introduction regarding several other studies showing no or even promoting effects of the antioxidant vitamin C on cataracts in humans.
http://www.stat.colu...001/vitamin.pdf

Funny! With vitamin K you say only clinical trials are admissible as evidence, but with vitamin C you bring up epidemiology to counter a clinical trial. It would have been nice if this study had tried to determine the effect of dose, but I guess we can reasonably assume that it is consistent with the idea of needing a balanced antioxidant network. Table 3 in PMID: 18541583 suggests that it is best to be above median in all antioxidants, followed by below median in all antioxidants, followed by being above and below median in different antioxidants. That's a really crude way of determining balance, though. I wonder if anyone has ever tried doing a full factorial experiment to determine an optimal antioxidant intake.

[krillin]

Are you guys still debating vitamin K? I'm going to keep taking my LEF K complex with all pertinent forms, including K1, MK4, and MK7 for now. If either of you guys ever conclusively wins this argument, let me know and I may consider a different supplement.

If you set safety concerns aside, that thing is actually a rational design, despite not having been rationally designed. The MK-4 dose was set years ago, apparently for economic reasons, since they never justified the small size. It turns out that 1 mg could be effective, since 1.5 mg is.

J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):15-21.
Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women.
Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y.
Nutritional Epidemiology Program, National Institute of Health and Nutrition, 1-23-1, Toyama, Shinjyuku-ku, Tokyo 162-8636, Japan.
Abstract

It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

PMID: 19352059

[Blue]

Your "equation" seems to be this statement "You're right, I was too lazy in picking a MK-7 dose. PMID: 18079608 reports that for MK-7, ng/ml = 0.061 (mcg/day from natto) + 2.525. PMID: 16469998 reports that for optimal carboxylation of OC women age 50-69 need MK-7 concentrations of 3.9 ng/ml and age 70+ need 6.4 ng/ml. Which translates into intakes of 22 and 64 mcg/day, respectively. 45 mcg/day is thus a reasonable dose for non-senior citizens." (To those confused the first sentence seems to refer to figure 2 in that study.)

Here you are combining two different studies which is very dubious since as already mentioned there are large interlaboratory differences in mesuring vitamin K. As well as taking the second dubious study far too seriously as mentioned earlier due its theory is being contradicted by experimental reality. Eyeballing figure 2 in this study you need only an concentration of around 0.4 ng/mL K1 to optimize uoOC:IOC if less than 50 years old. Which do is contrary to the real-world experimental results of 2.9 ng/mL K1 from other studies the study itself cites in the discussion!

I am saying that since we cannot combine studies due to the laboratory difficulties what mk7 intake will optimize uoOC:IOC is unknown. In contrast to K1 where we have several direct experimental studies of K1 intake and achieved uoOC:IOC indicating that at least 1000 mcg is needed.

You are right that they did not specifically examine the eyes for cataract development in the 5 mg K1 and 45 mg mk4 studies but if people had developed symptomatic catataracts that would have been caught when people were asked to report all the medical conditions developed during the study period at the end of the studies. Probably some people in both K and placebo groups developed cataracts which are fairly common in elderly people but there were no significant differences regarding this between the groups.

Regarding the one IHerb.com anecdotal case of elevated bilirubin that is worthless evidence. Elevated bilirubin by itself is not uncommon or dangerous and can be caused by numerous different conditions (for example, heavy alcohol intake). You can find some people have experienced adverse effects for every supplement Iherb.sell with more than a few comments. According to this logic we should not take any popular supplement. Again, if this was a common, synmptomatic effect this would have been noticed in the placebo controlled studies.

"These are silly arguments and not up to your usual standard. Menadione is for chemotherapy, not chemoprevention." Read the study, it was not a chemotherapy study. Unless you consider vitamin D to be chemotherapy.

Regarding vitamin C I asked you to look at the studies mentioned in the introduction of the cited study. To summarize, no controlled pure vitamin C studies and cataracts, only vitamin C + other substances and cataratcs, and of those 1 found a small positive effect (the one you cited) and 3 found no effect. Regardig epidemiology there are studies finding both increased and decrased cataracts from higher vitamin C intake from food and supplements.

Edited by Blue, 12 July 2010 - 07:23 PM.

[ampa]

Semin Thromb Hemost. 1995;21(4):357-63.
Observations on vitamin K deficiency in the fetus and newborn: has nature made a mistake?
Israels LG, Israels ED.
Department of Medicine, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Canada.

The microsomal mixed function oxidase system metabolizes xenobiotics (Phase I) to products that, if not activated and conjugated for excretion (Phase II), are capable of forming conjugates with cellular macromolecules, including DNA, resulting in toxic, mutagenic, or carcinogenic events. Benzo(a)pyrene (BP), a polycyclic aromatic hydrocarbon, is a model carcinogen for this system. Vitamin K1 (phylloquinone) is a regulator of BP metabolism. These studies demonstrate that K1 is capable of increasing Phase I metabolism and decreasing glutathione transferase activity (Phase II) in chick embryo liver; that deprivation of K1 reduces BP/DNA adducts in mouse liver and reduces tumor formation in mice given intraperitoneal BP; and that K1 supplementation increases BP induced tumor formation in mice. However, epidemiologic studies indicate that children of mothers who smoke during pregnancy may not be at increased risk of cancer. It is known that the placentas from these pregnancies exhibit markedly increased levels of arylhydrocarbon hydroxylase induced by the polycyclic aromatic hydrocarbons in tobacco smoke, but there is no corresponding increase in this enzyme activity in the fetus in such pregnancies. We suggest that the low vitamin K level is a secondary protective mechanism for xenobiotics, such as BP, that may escape the primary placental screen. The recently described role of vitamin K-dependent Gla protein as ligands for receptor tyrosine kinases, also establishes K as a link in cell growth and transformation. It is proposed that the small total body pool of K1 in the adult, which is sufficient only to meet continuing needs, and the even smaller pool in the fetus are protective. This protective effect of low K1 levels is particularly important in the presence of the high mitotic rates and rapid cell turnover in the avian embryo and mammalian fetus.

I missed this one, ouch. I had thought K1 was basically useless (in comparison with K2) but also harmless. I was running out of the LEF product anyway, I guess I'll go back to Jarrow's MK-7.

Hmmm...so just when I thought I'd cover all the bases and go with LEF's Super K I'm now wondering if K1 may have detrimental health effects? Is this K1-induced reduction of glutathione transferase activity clinically relevant? LEF's product has 1mg of K1 which seems relatively high if there is legitimate risk involved.

I really thought "Super K" was a great concept given all the debate over the various forms of vitamin K. Now I'm strongly considering just going with MK-7 (particularly for cardiovascular benefits). Does this seem reasonable?

[ThomasWH]

Butting in here...

I was taking NOW FOODS K2 (with Alfafa) for a year. But recently got a VERY high Hematocrit and Hemoglobin after being on Testosterone gel for a few months. I quit taking the NOW FOODS K2 beause I learned that the Alfafa in it turns into Vitamin K1, which again makes blood thicker. SO.... My Q is: Which K2 is the best one? I've read this thread for a few hours and it boils down to either taking MK-4 or MK-7. MK-4 sounds promising, but MK-7 is better researched. So... Should I take MK-7???

Jarrow's MK-7? Once daily?

Thomas

[e Volution]

Jarrow's MK-7? Once daily?

Yes, that is current best evidence based protocol...

[Sillewater]

Butting in here...

I was taking NOW FOODS K2 (with Alfafa) for a year. B

Also Now Foods is MK-4. Considering one probably needs at least 1mg (from Krillin's links) a day, 120mcg of MK-4 isn't very well-backed.

[ThomasWH]

Butting in here...

I was taking NOW FOODS K2 (with Alfafa) for a year. B

Also Now Foods is MK-4. Considering one probably needs at least 1mg (from Krillin's links) a day, 120mcg of MK-4 isn't very well-backed.

It doesn't say it's MK-4. I use iHerb.com. Can you give me a link to the product you're talking about? I'm about to order the Jarrow MK-7 one... The problem taking anything with alfafa in it is that it thickens blood (K1). And my HCT is already at 54. NOT a good number. It should be between 40 and 50. This is TRT doing this to me. Testosterone gel always makes blood thicker... I even drink 2000-3000 ml of water every day! AND take sea salt so I don't get why it's THAT thick. Hemoglobine is also up, as well is Red Blood Cells.

[rwac]

It doesn't say it's MK-4. I use iHerb.com. Can you give me a link to the product you're talking about? I'm about to order the Jarrow MK-7 one... The problem taking anything with alfafa in it is that it thickens blood (K1). And my HCT is already at 54. NOT a good number. It should be between 40 and 50. This is TRT doing this to me. Testosterone gel always makes blood thicker... I even drink 2000-3000 ml of water every day! AND take sea salt so I don't get why it's THAT thick. Hemoglobine is also up, as well is Red Blood Cells.

I believe ajnast4r asked NOW, and they said it was MK-4. You should send them a message too.

ANY of the K vitamins will increase clotting, not just K1. However, I don't know if it will actually affect HCT.

[ThomasWH]

It doesn't say it's MK-4. I use iHerb.com. Can you give me a link to the product you're talking about? I'm about to order the Jarrow MK-7 one... The problem taking anything with alfafa in it is that it thickens blood (K1). And my HCT is already at 54. NOT a good number. It should be between 40 and 50. This is TRT doing this to me. Testosterone gel always makes blood thicker... I even drink 2000-3000 ml of water every day! AND take sea salt so I don't get why it's THAT thick. Hemoglobine is also up, as well is Red Blood Cells.

I believe ajnast4r asked NOW, and they said it was MK-4. You should send them a message too.

ANY of the K vitamins will increase clotting, not just K1. However, I don't know if it will actually affect HCT.

So any K vitamin will increase what, Platelets? Isn't Platelets the factor for clotting? HCT just means blood is getting thicker, that's what I've heard. I'm not an expert. Yet. I want to take Vitamin K to remove plaque from my arteries.

See, I have an above range serum calcium even if I don't get much calcium in my non-diary diet. Can anyone explain that?

[rwac]

So any K vitamin will increase what, Platelets? Isn't Platelets the factor for clotting? HCT just means blood is getting thicker, that's what I've heard. I'm not an expert. Yet. I want to take Vitamin K to remove plaque from my arteries.

See, I have an above range serum calcium even if I don't get much calcium in my non-diary diet. Can anyone explain that?

Essentially vitamin K plays a role (gamma-carboxylation) in activating certain proteins related to clotting.
It should only thicken blood if you are using a blood thinner like warfarin, there have
been trials with large amounts (45mg/day) of MK-4.

It does normalize clotting, though. You will notice much faster clotting if you get hurt.

I don't know how this relates to a high HCT and your case particularly.

Edited by rwac, 11 October 2010 - 10:22 PM.

[FunkOdyssey]

Still taking the LEF K complex with K1, MK4 and MK7, and it's still cheaper than taking MK7 alone (wtf jarrow?). I'll check back in when we hit 20 pages on this thread.

[katzenjammer]

I'm so confused I've come to alternate between Relentless Improvement's mk4 (15 mg.) one day - and Jarrow's Mk7 the next. LOL.

[e Volution]

I'm so confused I've come to alternate between Relentless Improvement's mk4 (15 mg.) one day - and Jarrow's Mk7 the next. LOL.

I'm the same except I am running Carlson Labs MK-4 (5mg) 2-3 times/week and Jarrows MK-7 (90mcg) 2-3 times/week with a day or two off...

[niner]

It doesn't say it's MK-4. I use iHerb.com. Can you give me a link to the product you're talking about? I'm about to order the Jarrow MK-7 one... The problem taking anything with alfafa in it is that it thickens blood (K1). And my HCT is already at 54. NOT a good number. It should be between 40 and 50. This is TRT doing this to me. Testosterone gel always makes blood thicker... I even drink 2000-3000 ml of water every day! AND take sea salt so I don't get why it's THAT thick. Hemoglobine is also up, as well is Red Blood Cells.

How much sea salt are you taking? If you eat too much salt, it will dehydrate you, because it has to be eliminated via urine. Depending on who you talk to, a hct of 54 might be considered normal or only slightly high for an adult male. These guys claim normal is up to 62! Values might vary according to the method of determination of hct.

[ThomasWH]

It doesn't say it's MK-4. I use iHerb.com. Can you give me a link to the product you're talking about? I'm about to order the Jarrow MK-7 one... The problem taking anything with alfafa in it is that it thickens blood (K1). And my HCT is already at 54. NOT a good number. It should be between 40 and 50. This is TRT doing this to me. Testosterone gel always makes blood thicker... I even drink 2000-3000 ml of water every day! AND take sea salt so I don't get why it's THAT thick. Hemoglobine is also up, as well is Red Blood Cells.

How much sea salt are you taking? If you eat too much salt, it will dehydrate you, because it has to be eliminated via urine. Depending on who you talk to, a hct of 54 might be considered normal or only slightly high for an adult male. These guys claim normal is up to 62! Values might vary according to the method of determination of hct.

My local hospitals laboratory, and all labs in Norway, say 40 to 50 is the normal for HCT for men. I was always at 50, or a bit less, never above. Only after I started TESTOSTERONE TREATMENT, my HCT went up til 60 about 2 months aog. Had to quit the gel. HCT went back to 49-50. Now I've started taking Testosterone aain and HCT is back up, though only at 53 thus far. I drink 500 ml of water with 1/2 tea spoon of RAW sea salt daily. This is a normal amount of salt. I believe most people get more than that daily. I add some sea salt to my LEAN means as well. I never buy food WITH salt in it. I never touch table salt. I was taking 1 tea spoon sea salt for 8 months, and ya know what? HCT never went up while doing so. So it IS the Testosterone gel raising my HCT. I was on Vitamin E and K2 (NOW FOODS K2, not MK4 or MK7 btw!) for 1 year, while starting TRT 6 months ago. Maybe that kept my HCT down til I upped my Testosterone to twice the dose (2 pumps daily; 2 grams of gel; 200 mg testosterone) like 3 months ago. HCT didn't increase til I upped the Testosterone gel, while I was on K2 and E supplements. Now I am not taking K2 nor Vitamin E, and HCT is going up while only taking 3/4 pump of gel (0.7 grams; 75 mg of Testosterone) - I was taking the same amount of sea salt all this time while on Testosterone gel; 1/2 tea spoon daily. (NOT A LOT!)

I know too much salt can dehydrate you, but I have adrenal fatigue, and I probably need a higher salt intake than a regular healthy person. Tha tbeing said, I do not get a lot of salt every day. Only that 1/2 tea spoon of seal salt, and I am not even sure I am measuring the salt correctly. I should probably up my salt intake. My aldosterone is midrange, and could be a tad too low to actually USE the salt. I don't know. My face is bloated though. THAT could be from taking 35 mg of Hydrocortison daily. Before starting the HC on June 2009, my face was normal. HC is clearly puffing up my face a lot. My current hormone doc wants me to take HC, ERFA Thyroid, Testosterone gel and DHEA (and growth hormone) every day. So far, I am taking that, except the growth hormone.

I have a "probably" Secondary Hypopituitarism.

Thomas

[Brinksbury]

This is a response to something rwac said a while back.

You mentioned that you had softer facial skin and little/no dental plaque. I've had the same experience. I'd been taking 5 mg of mk4 daily (or so) and noticed my skin was softer. (I also take a lot of fish oil) At some point I went into the dentist for a routine cleaning and my dentist told me my teeth were 'perfect' - it was so strange. They usually find plenty of things that are wrong.

For the record I've been supplementing with other things related to calcium utilization/bone growth, such as manganese, boron, zinc, copper. I've even taken nickel & silicon which I had to procure myself.

I have no idea if this is related to anything, but I thought I'd post it anyway: http://www.springerl...t29vt80ynx1eax/ summary: Plaque causing bacteria are found in the gut as well as the arteries affected by atherosclerosis.

[Brinksbury]

Ok, there's something else I should say. I live near several Asian grocery stores, and I bought several boxes of Natto and managed to eat 5 or 6 of them. I could feel the mk7, it sped up my thought process (in a good way). However I didn't sleep all that soundly that night. I've since purchased the Jarrow mk7 and the Carlson 5mg mk4. I took the 45 mg dose of mk4 and didn't feel anything. There is definitely a difference between mk4 and mk7.

When I took mk4 and ate natto, I noticed that the feeling from the mk7 was extended for much longer than normal.

One last thing, the amount of mk7 in a single Jarrow softgel is paltry compared to a single serving of natto. Natto has way more, but how much more I can't say since its been a while since I tried all this out.

Since then I've stuck to just the mk4, but now I'm considering eating natto for breakfast again. (btw, the whole 'sped up though process' thing would seem to go with the Japanese only consuming Natto in the morning. Interesting?) ok. I hope my post wasn't too amateurish. My intention was to give my first hand account in the hopes it would add to the available knowledge.

[Tango2]

The mental effects of K2 were something that I noticed too when starting the NSI Advanced K2 supplement which is similar to Life Extension's (1400 mcg MK-4, 100 mcg MK-7). I had increased clarity of thought, faster thought and better nerve functioning in my autonomous system. This was very unexpected because I was taking Vitamin K2 for future cardiac and bone benefits. In some research there is an indication that K2 helps in the myelination of nerve cells which would make them better insulated and perhaps more functional. I have also had moderate RLS (Restless Legs Syndrome)at night and while sitting that disturbed my sleep for about ten years. The RLS was rapidly reduced by about 98% as another positive outcome!

There is some indication of nerve activity at: http://trit.us/basic...-k2.html#closer
Quote:
Vitamin K2 and the Brain: A Closer Look

The concentration of vitamin K2 is higher in myelinated regions than in non-myelinated regions of the brain (myelin is the sheath that forms the electrical insulation of neurons) and it is correlated with the presence of important lipids such as sphingomyelin and sulfatides. The small amount of K1, by contrast, is distributed more randomly,73 suggesting that it may not be as functionally important. These lipids are part of a broader class of compounds called sphingolipids that play essential roles in the brain as structural constituents of membranes, signaling factors, and promoters of cell survival. Vitamin K2 supports the activity of the enzyme that catalyzes the initial reaction for the production of all sphingolipids as well as the enzyme that catalyzes the final step in the synthesis of sulfatides. Warfarin or dietary vitamin K deficiency cause marked decreases in the activities of these enzymes and of the levels of sulfatides in the brains of rats and mice, while the administration of either vitamin K1 or K2 restores them.46
End quote

I have also found an increase in my energy level, perhaps due to the mitochrondrial K2 involvement also mentioned there. As a possible result I can run slightly faster and have more mental stamina. If this is related to the MK-7 fraction, it would be interesting to test for similar mental effects in Japan along the geographical distributions of Natto consumption. My brain function was so changed that I felt in an unrecognizable new mood for a couple of days.

From my understanding about doses, a Natto serving would provide about 1100 MCG of MK-7 which would well exceed my experience with the 100 mcg in my NSI supplement above. I wonder if the body was given a large, consistent dose it might self adjust out of the insomnia which I've not experienced. I take my K2 in the morning BTW. From other sources, the MK-4 fraction blood level peaks in about 2-3 hours and the MK-7 fraction peaks over about ten hours. This was tested by Dutch researchers measuring ucCO/iCO levels for both.
- Dave

Ok, there's something else I should say. I live near several Asian grocery stores, and I bought several boxes of Natto and managed to eat 5 or 6 of them. I could feel the mk7, it sped up my thought process (in a good way). However I didn't sleep all that soundly that night. I've since purchased the Jarrow mk7 and the Carlson 5mg mk4. I took the 45 mg dose of mk4 and didn't feel anything. There is definitely a difference between mk4 and mk7.

When I took mk4 and ate natto, I noticed that the feeling from the mk7 was extended for much longer than normal.

One last thing, the amount of mk7 in a single Jarrow softgel is paltry compared to a single serving of natto. Natto has way more, but how much more I can't say since its been a while since I tried all this out.

Since then I've stuck to just the mk4, but now I'm considering eating natto for breakfast again. (btw, the whole 'sped up though process' thing would seem to go with the Japanese only consuming Natto in the morning. Interesting?) ok. I hope my post wasn't too amateurish. My intention was to give my first hand account in the hopes it would add to the available knowledge.