350 replies to this topic

[Blue]

Negative analysis of superhigh mk4 supplemenation trials:
http://ddr.nal.usda....IND44157619.pdf

Looks like mk7 may be better at least from epidemiological data.

[stephen_b]

Negative analysis of superhigh mk4 supplemenation trials:
http://ddr.nal.usda....IND44157619.pdf

Looks like mk7 may be better at least from epidemiological data.

I don't read this as negative analysis of MK-4:

The reported outcomes of clinical trials, primarily from Japan, that have assessed the effect of MK-4 treatment on fracture risk and bone loss at the spine are positive overall. However, the doses used in these trials are over 400-fold higher than the current recommended intakes of vitamin K. Recent reports of the lack of a protective effect of MK-4 on bone loss at the hip or on hip fracture risk suggest that a prior meta-analysis needs to be revisited.

They are saying that the prior meta-analysis needs to be revisited since its conclusions regarding MK-4's effect on bone loss are possibly in error.

The paper is negative towards phylloquinone (K1). So am I. I have no trouble favoring MK-7 over K1. I still lean toward MK-4 as the best form. The body converts K1 to K2-MK4 probably for a reason.

Nice write-up at Weston Price:

Fermented foods such as sauerkraut, cheese, and natto, a soy dish popular in Eastern Japan, contain substantial amounts of vitamin K2. Natto, in fact, contains the highest amount of any food measured; nearly all of it is present as MK-7.26 MK-7 is highly effective: one recent study showed that it increased the percentage of activated osteocalcin in humans three times more powerfully than did vitamin K1.32 There are no studies available, however, comparing the efficacy of MK-7 to that of the MK-4 found in animal products. MK-9, and presumably MK-7, stays in the blood for a longer period of time than does MK-4, but this appears to be because tissues take up MK-4 much more rapidly.30 Whether the rapid uptake of MK-4 or the longer time spent in the blood by bacterial menaquinones have particular benefits or drawbacks is unclear. Future research will have to clarify whether the vitamin K2 synthesized by animal tissues and by bacteria are interchangeable, whether one is superior to the other, or whether each presents its own unique value to our health.

26. Schurgers LJ, Vermeer C. Determination of Phylloquinone and Menaquinones in Food. Haemostasis. 2000; 30: 298-307.
30. Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta. 2002; 1570: 27-32.
32. Schurgers LJ, Teunissen KJF, Hamulyak K, Knapen MHJ, Hogne V, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2006; [Epub ahead of print].

StephenB

[Blue]

I don't read this as negative analysis of MK-4:


They are saying that the prior meta-analysis needs to be revisited since its conclusions regarding MK-4's effect on bone loss are possibly in error.

The paper is negative towards phylloquinone (K1). So am I. I have no trouble favoring MK-7 over K1. I still lean toward MK-4 as the best form.

I see the paper as much more neative regarding mk4. The studies excluded from the previous meta-analysis are the more important ones. More recent, larger, placebo controlled studies finding no effect. "As discussed by the authors, several of the studies used for the meta-analysis lacked sufficient sample size, were non-placebo-controlled intervention trials, and/or used concurrent treatment with calcium and/or vitamin D."

Edited by Blue, 23 July 2009 - 04:20 PM.

[stephen_b]

I see the paper as much more neative regarding mk4.

I don't think you are reading it right.

The reported outcomes of clinical trials, primarily from Japan, that have assessed the effect of MK-4 treatment on fracture risk and bone loss at the spine are positive overall. However, the doses used in these trials are over 400-fold higher than the current recommended intakes of vitamin K. Recent reports of the lack of a protective effect of MK-4 on bone loss at the hip or on hip fracture risk suggest that a prior meta-analysis needs to be revisited

It's saying 1) MK-4 treatment is positive overall and 2) prior meta-analysis not showing benefits is quite possibly wrong.

[Blue]

I don't think you are reading it right.



It's saying 1) MK-4 treatment is positive overall and 2) prior meta-analysis not showing benefits is quite possibly wrong.

How can "Recent reports of the lack of a protective effect of MK-4 on bone loss at the hip or on hip fracture" mean that a prior-meta-analysis supposedly showing no benefits was wrong? Should just reinforce. Please reread. The previous meta-analyis was positive which is most likely incorrect due to more recent, larger, placebo-controlled studies showing no effect.

Edited by Blue, 23 July 2009 - 05:03 PM.

[stephen_b]

How can "Recent reports of the lack of a protective effect of MK-4 on bone loss at the hip or on hip fracture" mean that a prior-meta-analysis supposedly showing no benefits was wrong?

The recent reports are the prior-meta-analysis. They are implying these are wrong.

[Blue]

The recent reports are the prior-meta-analysis. They are implying these are wrong.

No, the prior, poor meta-analysis showed a protective effect of mk4. The recent, larger, placebo-controlled studies find no effect.

[Blue]

Here is the previous meta-analysis this study think is wrong:
http://archinte.high...act/166/12/1256

[kismet]

No, the prior, poor meta-analysis showed a protective effect of mk4. The recent, larger, placebo-controlled studies find no effect.

Are you jumping the gun? (again) "Poor meta-analysis", the authors think it is "wrong"? It is very interesting that I can't find those particular words in the paper you are quoting.

First, whatever the authors imply, their opinion is neither sacrosanct nor necessarily shared by their peers:
Nutr Res. 2009 Apr;29(4):221-8. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Iwamoto J, Sato Y, Takeda T, Matsumoto H.

My interpretation of their article is as follows (and I'm arguing from my reading of the vitamin K literature and their conclusion, but if I get to it I'll read the whole paper), the authors state that prior data needs to be "revisited", not that it is wrong. It would take quite a lot of negative data to overthrow those RRs:  "Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures." (from the 06 meta-analysis)

Their table is also very misleading if you are not very careful, they're only quoting BMD data. IIRC the data on vitamin K and BMD was always rather weak. The data on fracture risk is still overwhelmingly positive. I can't find any data challanging those RRs. See for instance one newer paper they mention, Knapen et al. found no effect on BMD, but in the same vein of the old meta-analysis they found improved indices of bone strength:

"Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake...Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD."

Edited by kismet, 23 July 2009 - 09:22 PM.

[JLL]

The reported outcomes of clinical trials, primarily from Japan, that have assessed the effect of MK-4 treatment on fracture risk and bone loss at the spine are positive overall. However, the doses used in these trials are over 400-fold higher than the current recommended intakes of vitamin K. Recent reports of the lack of a protective effect of MK-4 on bone loss at the hip or on hip fracture risk suggest that a prior meta-analysis needs to be revisited

It's saying 1) MK-4 treatment is positive overall and 2) prior meta-analysis not showing benefits is quite possibly wrong.

Wow, talk about a difficult paragraph.

It seems to me, though, that they are saying:

1) Clinical trials have shown positive results...
2) ...but this is because they used doses that are over 400-fold higher than recommended...
3) ...plus, there's a couple of new reports showing no benefits...
4) ...which is why we should take another look at the prior meta-analysis which is probably wrong

[Blue]

Are you jumping the gun? (again) "Poor meta-analysis", the authors think it is "wrong"? It is very interesting that I can't find those particular words in the paper you are quoting.

First, whatever the authors imply, their opinion is neither sacrosanct nor necessarily shared by their peers:
Nutr Res. 2009 Apr;29(4):221-8. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Iwamoto J, Sato Y, Takeda T, Matsumoto H.

My interpretation of their article is as follows (and I'm arguing from my reading of the vitamin K literature and their conclusion, but if I get to it I'll read the whole paper), the authors state that prior data needs to be "revisited", not that it is wrong. It would take quite a lot of negative data to overthrow those RRs: "Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures." (from the 06 meta-analysis)

Their table is also very misleading if you are not very careful, they're only quoting BMD data. IIRC the data on vitamin K and BMD was always rather weak. The data on fracture risk is still overwhelmingly positive. I can't find any data challanging those RRs. See for instance one newer paper they mention, Knapen et al. found no effect on BMD, but in the same vein of the old meta-analysis they found improved indices of bone strength:

"Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake...Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD."

Good point about BMD being less important than bone quality for the vitamin K effect. That is a flaw in the critique of the meta-analysis. Fractures are more important than BMD. Still, fractures was also mentioned. To quote from the critique:

"It was subsequently disclosed that a large unpublished surveillance study conducted in Japan (n > 3000) did not find a protective effect of MK-4 supplementation (45 mg/day) on bone loss and fracture in the elderly, and that inclusion of this study may have altered the results of the meta-analysis."

I do not know if the previous fracture studies were among those with flawed design but if so this would obviously affect the results.

The later review you mention argues that both K1 and K2 reduce fractures:
http://www.ncbi.nlm....pubmed/19410972

Here is a study that found that 1 mg K1 or 45 mg MK-4 did not improve "proximal femur geometric parameters", presumably related to bone quality, for those already receiving calcium and vitamin D supplementation:
http://www.jbmronlin...359/jbmr.081254

On the other hand, another study found that 5 mg K1 reduced both fractures and cancer. Although not many of either in the study:
http://www.ncbi.nlm....pubmed/18922041

MK-7-9 best against CHD?
"After adjustment for traditional risk factors and dietary factors, we observed an inverse association between vitamin K₂ and risk of CHD with a Hazard Ratio (HR) of 0.91 [95% CI 0.85–1.00] per 10 μg/d vitamin K₂ intake. This association was mainly due to vitamin K₂ subtypes MK-7, MK-8 and MK-9. Vitamin K₁ intake was not significantly related to CHD."
http://www.sciencedi...8fdbc747e6a1196

Edited by Blue, 24 July 2009 - 11:31 AM.

[Blue]

"The triage theory posits that some functions of micronutrients (the 40 essential vitamins, minerals, fatty acids, and amino acids) are restricted during shortage and that functions required for short-term survival take precedence over those that are less essential. Insidious changes accumulate as a consequence of restriction, which increases the risk of diseases of aging. For 16 known vitamin K–dependent (VKD) proteins, we evaluated the relative lethality of 11 known mouse knockout mutants to categorize essentiality. Results indicate that 5 VKD proteins that are required for coagulation had critical functions (knockouts were embryonic lethal), whereas the knockouts of 5 less critical VKD proteins [osteocalcin, matrix Gla protein (Mgp), growth arrest specific protein 6, transforming growth factor β–inducible protein (Tgfbi or βig-h3), and periostin] survived at least through weaning. The VKD -carboxylation of the 5 essential VKD proteins in the liver and the 5 nonessential proteins in nonhepatic tissues sets up a dichotomy that takes advantage of the preferential distribution of dietary vitamin K1 to the liver to preserve coagulation function when vitamin K1 is limiting. Genetic loss of less critical VKD proteins, dietary vitamin K inadequacy, human polymorphisms or mutations, and vitamin K deficiency induced by chronic anticoagulant (warfarin/coumadin) therapy are all linked to age-associated conditions: bone fragility after estrogen loss (osteocalcin) and arterial calcification linked to cardiovascular disease (Mgp). There is increased spontaneous cancer in Tgfbi mouse knockouts, and knockdown of Tgfbi causes mitotic spindle abnormalities. A triage perspective reinforces recommendations of some experts that much of the population and warfarin/coumadin patients may not receive sufficient vitamin K for optimal function of VKD proteins that are important to maintain long-term health."
http://www.ajcn.org/...cn.2009.27930v1

[VesperLynd]

Hi, I've read through this thread a couple times trying to get a bottom line understanding on recommendations for supplementation.

If I understand it all correctly, MK-4 supports bone health (and anecdotally skin and teeth)... MK-7 supports arterial/coronary health.

Do I have this correctly and if so, what are the recommended dosages or brands/formulations?

Thanks, VL

[VespeneGas]

Hi, I've read through this thread a couple times trying to get a bottom line understanding on recommendations for supplementation.

If I understand it all correctly, MK-4 supports bone health (and anecdotally skin and teeth)... MK-7 supports arterial/coronary health.

Do I have this correctly and if so, what are the recommended dosages or brands/formulations?

Thanks, VL

The idea is that vitamin K2 carboxylates (activates) two proteins which regulate calcium metabolism (matrix gla protein and osteocalcin). This should help prevent arterial calcification (thus protecting the heart) and promote the deposition of calcium in bones (thus helping prevent osteoporosis). According to this source, osteocalcin may also help prevent insulin resistance and obesity.

Although unconfirmed by clinical trials, Dr. Weston price found that supplementing diet with foods high in K2 reduced bacterial growth in the mouth. MK4 appears to concentrate in the salivary glands of rats, FWIW, and people on imminst report reductions in dental plaque. There is some speculation around here that vitamin K2 can disrupt bacterial biofilms through the activity of the calcium-binding proteins they activate.

MK4 and MK7 are different versions of the same vitamin, and there's some debate about which form is superior (more research is needed). MK7 has a longer half-life in the body than MK4, and it's cheaper, which is why a lot of us take it. But both forms should (in theory) have the same beneficial effects in the body.

For MK4, 1 mg/day is about the most anyone gets from diet, while doses up to 15 mg/day are being investigated for reducing atherosclerosis. I wouldn't recommend taking more than 2 mg/day, as menaquinones break down into menadione, which is toxic. The usual dose for MK7 is 90 mcg/day.

I believe all this information can be found earlier in the thread

[Blue]

I have tried to look into this but what form is best is not obvious. K1 can can be converted to MK4 (K2 subtype). Both are present in tissues. In this rodent study K1 in the diet actually increases MK4 in the tissues more than MK4 in the diet. MK4 in the diet decreases MK4 levels in the brain. Weird BBB effect? In the heart and the liver K1 tissue levels are high, much higher than MK4, and increased by K1 but not by MK4.
http://jn.nutrition....t/126/2/537.pdf

But in the dietary Rotterdam study it is only K2 that protects against vascular calcification and improves all-cause mortality.
http://www.ncbi.nlm....pubmed/15514282

Supported by a rodent study:
http://content.karge...roduktNr=224160

In one dietary study this is due to MK7-9 subtypes of K2:
http://www.ncbi.nlm....pubmed/19179058

K2 but not K1 protects against prostate cancer in one dietary study. In particular K2 from diary products as opposed to meat. That may mean more MK7-9, found in high amounts in cheese, as compared to MK4.:
http://ecnis.openrep...dle/10146/36855

But dietary and animal studies have time and time again shown to be unreliable.

Trial studies in Japan have used very high doses of MK4 and found strong effects against fractures:
http://archinte.high...act/166/12/1256

MK4 also improved recurrence of liver cancer in two , but not another one, small studies:
http://www3.intersci...225124/abstract
http://www3.intersci...534022/abstract
http://ci.nii.ac.jp/naid/110006980526/

Trials with high-dose KI also reduce the risk of fractures:
http://linkinghub.el...271531709000578

5 mg of K1 strongly protected against cancer and fractures in one relatively small study:
http://www.ncbi.nlm....pubmed/18922041

There seems to be no trials with MK7.

Edited by Blue, 13 October 2009 - 10:01 AM.

[Blue]

Looking at the dietary studies the intake ranges are quite narrow and the intake quite small compared to those used in placebo trials. In prostate cancer dietary study intake were for median values and lowest and highest quartile inside the parenthesis: K1 93.6 (70.9–123.5) mcg, MK4 14.4 (10.9–18.7) mcg, MK-5–9 18.0 (11.7–27.0) mcg, MK-7 0.8 (0.5–1.1) mcg. So for example the K1 intake may have been to narrow and small to see any effect as compared to x50 larger amount in the 5 mg K1 placebo study.

Edited by Blue, 13 October 2009 - 12:13 PM.

[VesperLynd]

Thank you all for the thoughtful discussion and helping me sort through the information.

Is there any speculation as to what might be spurring the anecdotal reports of improvements in skin texture?

Thanks, VL

[Blue]

Thank you all for the thoughtful discussion and helping me sort through the information.

Is there any speculation as to what might be spurring the anecdotal reports of improvements in skin texture?

Thanks, VL

None that I have seen. But K1 or K1 actively converted to MK4 are found in many tissues and not just the liver and bone. Presumably it is doing something beyond clotting and bone formation. I can also add my experience to the others that MK4 greatly improves dental smoothness. I have only used a relatively low dose 90 mcg. Maybe I will try high dose K1 in the future and see if I get the same effect.

[VespeneGas]

Blue, sorry if you're already aware of this, but rats have intestinal flora which convert K1 into MK4 quite effectively, whereas our gut buddies make this conversion to a negligible degree, IIRC.

Not disagreeing with your reasoning, just thought it deserves pointing out that K1 probably won't significantly increase tissue MK4 in people.

[Blue]

Blue, sorry if you're already aware of this, but rats have intestinal flora which convert K1 into MK4 quite effectively, whereas our gut buddies make this conversion to a negligible degree, IIRC.

Not disagreeing with your reasoning, just thought it deserves pointing out that K1 probably won't significantly increase tissue MK4 in people.

No need to feel sorry. The intestinal flora is not involved.

The ability of male rats to accumulate menaquinone-4 (MK-4) in tissues when fed a vitamin K-deficient diet supplemented with intraperitoneal phylloquinone (K) as the sole source of vitamin K for 14 d was assessed. In both conventionally housed controls and gnotobiotic rats, supplementation with the equivalent of 1500 µg vitamin K/kg diet increased (P < 0.001) tissue MK-4 concentrations above those of controls fed a vitamin K-deficient diet. MK-4 concentrations were ~5 ng/g (11 pmol/g) in liver, 14 ng/g in heart, 17 ng/g in kidney, 50 ng/g in brain and 250 ng/g in mandibular salivary glands of gnotobiotic rats. MK-4 concentrations in conventionally housed rats were higher than in gnotobiotic rats in heart (P < 0.01), brain (P < 0.01) and kidney (P < 0.05) but lower in salivary gland (P < 0.05). Cultures of a kidney-derived cell line (293) converted K to the epoxide of MK-4 in a manner that was dependent on both time of incubation and concentration of vitamin K in the media. A liver-derived cell line (H-35) was less active in carrying out this conversion. These data offer conclusive proof that the tissue-specific formation of MK-4 from K is a metabolic transformation that does not require bacterial transformation to menadione as an intermediate in the process.
http://jn.nutrition....pe2=tf_ipsecsha

To elucidate the role of intestinal bacteria in the conversion of phylloquinone into menaquinone-4 (MK-4) we investigated the tissue distribution of vitamin K in germ-free rats. The rats were made vitamin K deficient by feeding a vitamin K-free diet for 13 days. In a subsequent period of 6 days, phylloquinone and menadione were supplied via the drinking water in concentrations of 10 and 50 micromol l(-1). Menadione supplementation led to high levels of tissue MK-4, particularly in extrahepatic tissues like pancreas, aorta, fat and brain. Liver and serum were low in MK-4. Phylloquinone supplementation resulted in higher phylloquinone levels in all tissues when compared with vitamin K-deficient values. The main target organs were liver, heart and fat. Remarkably, tissue MK-4 levels were also higher after the phylloquinone supplementation. The MK-4 tissue distribution pattern after phylloquinone intake was comparable with that found after menadione intake. Our results demonstrate that the conversion of phylloquinone into MK-4 in extrahepatic tissues may occur in the absence of an intestinal bacterial population and is tissue specific. A specific function for extrahepatic MK-4 or a reason for this biochemical conversion of phylloquinone into MK-4 remains unclear thus far.
http://www.ncbi.nlm....4?dopt=Abstract

[VespeneGas]

Blue, sorry if you're already aware of this, but rats have intestinal flora which convert K1 into MK4 quite effectively, whereas our gut buddies make this conversion to a negligible degree, IIRC.

Not disagreeing with your reasoning, just thought it deserves pointing out that K1 probably won't significantly increase tissue MK4 in people.

No need to feel sorry. The intestinal flora is not involved.

The ability of male rats to accumulate menaquinone-4 (MK-4) in tissues when fed a vitamin K-deficient diet supplemented with intraperitoneal phylloquinone (K) as the sole source of vitamin K for 14 d was assessed. In both conventionally housed controls and gnotobiotic rats, supplementation with the equivalent of 1500 µg vitamin K/kg diet increased (P < 0.001) tissue MK-4 concentrations above those of controls fed a vitamin K-deficient diet. MK-4 concentrations were ~5 ng/g (11 pmol/g) in liver, 14 ng/g in heart, 17 ng/g in kidney, 50 ng/g in brain and 250 ng/g in mandibular salivary glands of gnotobiotic rats. MK-4 concentrations in conventionally housed rats were higher than in gnotobiotic rats in heart (P < 0.01), brain (P < 0.01) and kidney (P < 0.05) but lower in salivary gland (P < 0.05). Cultures of a kidney-derived cell line (293) converted K to the epoxide of MK-4 in a manner that was dependent on both time of incubation and concentration of vitamin K in the media. A liver-derived cell line (H-35) was less active in carrying out this conversion. These data offer conclusive proof that the tissue-specific formation of MK-4 from K is a metabolic transformation that does not require bacterial transformation to menadione as an intermediate in the process.
http://jn.nutrition....pe2=tf_ipsecsha

To elucidate the role of intestinal bacteria in the conversion of phylloquinone into menaquinone-4 (MK-4) we investigated the tissue distribution of vitamin K in germ-free rats. The rats were made vitamin K deficient by feeding a vitamin K-free diet for 13 days. In a subsequent period of 6 days, phylloquinone and menadione were supplied via the drinking water in concentrations of 10 and 50 micromol l(-1). Menadione supplementation led to high levels of tissue MK-4, particularly in extrahepatic tissues like pancreas, aorta, fat and brain. Liver and serum were low in MK-4. Phylloquinone supplementation resulted in higher phylloquinone levels in all tissues when compared with vitamin K-deficient values. The main target organs were liver, heart and fat. Remarkably, tissue MK-4 levels were also higher after the phylloquinone supplementation. The MK-4 tissue distribution pattern after phylloquinone intake was comparable with that found after menadione intake. Our results demonstrate that the conversion of phylloquinone into MK-4 in extrahepatic tissues may occur in the absence of an intestinal bacterial population and is tissue specific. A specific function for extrahepatic MK-4 or a reason for this biochemical conversion of phylloquinone into MK-4 remains unclear thus far.
http://www.ncbi.nlm....4?dopt=Abstract

Fascinating. I wonder to what extent these extrahepatic conversions happen in humans.

[health_nutty]

This is an overview that showed MK-7 to be the superior form (although the article is clearly biased):

http://docs.google.c...esYmdipE7w9edIw

[rwac]

This is an overview that showed MK-7 to be the superior form (although the article is clearly biased):

It's only comparing K1 to MK-7. No mention of MK-4 at all.

[Blue]

This is an overview that showed MK-7 to be the superior form (although the article is clearly biased):

http://docs.google.c...esYmdipE7w9edIw

The complete study is here:
http://bloodjournal....full/109/8/3279

MK7 has a stronger effect than K1 mcg for mcg on the ratio between circulating carboxylated / undercarboxylated osteocalcin and on coagulation. On the other hand K1 is much less expensive. What is best of say 1 mg K1 and 200 mcg MK7? Unclear.

Edited by Blue, 14 October 2009 - 06:33 AM.

[Blue]

If wanting a low dose of menadione (K3), a metabolite of the Ks, then MK7 is preferable to the other forms. But menadione seems to be a problem mainly for special groups such as newborns and those with G6PD deficiency. There are no trial studies of MK7. It is not clear that it present in significant amounts outside the circulatory system or can do what K1 and MK4 has been shown to do outside the circulatory system. Or if it is converted to MK4 that it can achieve as high tissue concentrations as K1 and MK4 with a much lower dose. If taking MK7 you are betting on the epidemiological dietary correlations which are always uncertain and not comparable to the supplementary amounts which are much higher than the amounts seen in the diet.

[Blue]

On the other hand, natto eaters in Japan get similar MK7 blood levels to those seen from 0.22 µmol (=around 130 mcg) of MK-7 in the study above (around 6 ng/ml).

"Increasing evidence indicates a significant role for vitamin K in bone metabolism and osteoporosis. In this study, we found a large geographic difference in serum vitamin K2 (menaquinone-7; MK-7) levels in postmenopausal women. 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. We investigated the effect of Japanese fermented soybean food, natto, on serum vitamin K levels. Natto contains a large amount of MK-7 and is eaten frequently in eastern (Tokyo) but seldom in western (Hiroshima) Japan. Serum concentrations of MK-7 were significantly higher in frequent natto eaters, and natto intake resulted in a marked, sustained increase in serum MK-7 concentration. We analyzed the relation between the regional difference in natto intake and fracture incidence. A statistically significant inverse correlation was found between incidence of hip fractures in women and natto consumption in each prefecture throughout Japan. These findings indicate that the large geographic difference in MK-7 levels may be ascribed, at least in part, to natto intake and suggest the possibility that higher MK-7 level resulting from natto consumption may contribute to the relatively lower fracture risk in Japanese women."
http://www.sciencedi...a2eef998d95c584

Edited by Blue, 14 October 2009 - 10:19 AM.

[Ami]

Seems like LEF's Super K should cover all the bases?

[Blue]

Seems like LEF's Super K should cover all the bases?

Has all forms. But not the supermegadoses of 45 mg MK4 used in the Japanese osteoporosis studies (x1000 normal dietary intake!). Or the 5 mg of K1 used in the (small) study which saw a great reduction in cancers. I do not think anyone know if the Ks interact with one another in a good or bad way.

NSI also has come combination Ks:
http://www.vitacost....nced-K2-Complex
http://www.vitacost....mcg-90-Softgels

[immortali457]

I've been taking this one from NSI http://www.vitacost....m-Natto-Extract
I will buy the one in the first link above next time. Let the NSI bashing begin...lol

[kismet]

If taking MK7 you are betting on the epidemiological dietary correlations which are always uncertain and not comparable to the supplementary amounts which are much higher than the amounts seen in the diet.

But the mechanistical and epidemiologic evidence for MK-7 is incredibly strong. Carboxylation is the only known physiologic function of vitamin K and MK-7 does it better in vitro, in vivo and in humans. Most epidemiology finds associations with MK-7 not MK-4 or phylloquinone. It's clearly the best choice based on epidemiology and pharmakokinetics.
Recently I've also started to appreciate K1 (@1000mcg), because it's the only form backed by relevant clinical evidence. It's clearly the best choice based on clinical evidence.

MK-4 is inferior in all regards. All successful trials use unnatural mega doses (menadione metabolism - probably not a problem at 1000mcg but at 45000? lack of evolutionary adaptation?), usually 45mg, and it's used to treat, not prevent disease. So the data tells us nothing about aging and prevention. We do not suffer from hepatic cancer or osteporosis. So it's clearly inferior for anyone who's not at risk of osteoporosis.

Edited by kismet, 15 October 2009 - 10:34 AM.