Vitamin K1 Vs. K2 And How Much To Take With Aspirin?

Mossy

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I find this substantial as well, because the MK4 supplement I am taking is only designed for external (topical) use, which does not seem to be the best delivery for the substance
Interesting. So, it would seem topical and oral would cover all the bases.
 

YourUniverse

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Anecdote - my blood pressure dropped from ~145/85 (my blood pressure has been puzzling me for a few months, I've posted about it more than a few times here...) to ~130/85 after 6 days of drinking kale/spinach/salt broth (very rich in minerals and vitamin K). This is the first green vegetable nutrition I've had since Christmas (roughly speaking). I used to be able to "feel" the high blood pressure; I'd take basically stress breaths every minute or so, and feel like a slight buzz in my extremities, which freaked me out, until I got used to it. The tingling in my extremities is now gone, and blood pressure is confirmed to be down.

Could be many things, sure. My lifestyle is basically the same. My diet is basically the same, + green broth.

If anyone is interested in making the broth, I recommend googling "Kate Deering mineral broth" for the simple recipe (and her book based on Peat's work, "How to Heal your Metabolism", is definitely worth reading, especially for any noobies).

Edit: Want to point out that this blood pressure decrease is with higher coffee intake than previous, too. This is important I think because I recently made a post about restricting coffee to have more nutrition, but I didnt feel as good going off coffee, so I went back, and added the mineral broth, and still have the lowered BP.
 
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kayumochi

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I see references all around about Peat saying to take vitamin K to offset aspirins thinning of the blood. However, it never says Vitamin K1 or K2, it just says Vitamin K. I see people saying they take Vitamin K2, but I thought K2 was more for bone health, and K1 is more for clotting factor. So which one is Ray Peat referring to when he says to take some vitamin K along with aspirin? And how much should be taken? Is there a correct ratio to try for? Is there any signs that show up if you are not getting enough K with your Aspirin? Maybe like bloody noses or something....


7-8 drops of Kuinone daily (oral) eliminates all aspirin-related bruising for me.
 

haidut

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haidut

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I had in mind the 500 mcg of K1 and 150 mcg of MK-4 batch that we talked about before, but it's up to you to separate them or not. You already asked your supplier..

You don't think 500mcg K1 would be a bit too much and maybe risk a clot event? I would have thought the opposite ratio would be better - 500mcg MK-4 and 150mcg K1.
I can make a bottle for you and if you really like it then you can share your story and we can make it into a separate product for everybody.
 

Amazoniac

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You don't think 500mcg K1 would be a bit too much and maybe risk a clot event? I would have thought the opposite ratio would be better - 500mcg MK-4 and 150mcg K1.
I can make a bottle for you and if you really like it then you can share your story and we can make it into a separate product for everybody.
What if I die? Will you at least be present at the funeral?
I was thinking of waiting for others' deaths first, and if none was reported, I could then try.

Here they used up to 2000 mcg without such (†) events:
A high phylloquinone intake is required to achieve maximal osteocalcin γ-carboxylation

I never tried K1 before, so I'm willing to for the sake of curiosity, I volunteer.
 

haidut

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What if I die? Will you at least be present at the funeral?
I was thinking of waiting for others' deaths first, and if none was reported, I could then try.

Here they used up to 2000 mcg without such (†) events:
A high phylloquinone intake is required to achieve maximal osteocalcin γ-carboxylation

I never tried K1 before, so I'm willing to for the sake of curiosity, I volunteer.

OK, so I will try to make a solution with K1:MK-4 in a 3:1 ratio. Probably 300mcg K1 and 100mcg MK-4 per drop.
 

haidut

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I already has your K2, so just K1 initially will make it easier to note its effects, it will also simplify for you. Why 300 mcg?

To lower risk of accidental overdose. If it has say 1mg+ per drop it is quite easy to put a few milligrams too many on the skin or ingest them accidentally.
 

Amazoniac

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To lower risk of accidental overdose. If it has say 1mg+ per drop it is quite easy to put a few milligrams too many on the skin or ingest them accidentally.
As commented on the previous page, if I were to sell such supplement, I would put 500 mcg of K1 per serving that requires 3 (or 2) drops; so it's matching what you have in mind.
 

haidut

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As commented on the previous page, if I were to sell such supplement, I would put 500 mcg of K1 per serving that requires 3 (or 2) drops; so it's matching what you have in mind.

OK, I will let you know when it is ready. Should have it by end of this week or beginning of next.
 

Amazoniac

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I have performed quite a few tests with high dose K2, be careful for oxidative damage signs. I know what it should do, sometimes less is more, especially in delicate situations. Ditto your vit D supplementation, in my experience and observation, a lot of 'kidney patients' do badly on supplemental D. I suspect, but am not sure, that the added calcium uptake it encourages doesn't get used properly and does what it shouldn't according to theory.
That's why I commented before that it must be preferable to leave for K1 what it can do best, covering the basics with it, and then adding the freed Mk-4 as needed. The experiments that used higher doses (up to 135 mg/d) opened new possibilities, but encouraged visible mass overdosing.

I also suspect (contrary to what I read) that K1 is more resistant to depletion from vitamin E. Mk-4* is supposed to be taken throughout the day if the goal is to cover all of vit K functions without resorting to pharmacological doses, but people use a massive amount of it and later supplement extreme amounts of vitamin E as well, and it must be weird for the body to be swinging like that.

*Zeus must have questioned why is it not Mq-4, and from then the Kuinone name was born.

If there are some conditions that require more (such as in people with kidney issues: they have lower detectable levels in spite of consuming normal amounts) due to malabsorption, poor recycling, loss, fast consumption in the body, vit K can only be replenished on the next dose or from what remains circulating for longer. I know it sounds obvious but in practice it's often ignored when someone takes a single shot.
Having excess of vit D from supplements is another reason to favor lower and more frequent amounts: we still don't know how long the mk-4 effects last in tissues.

But in terms blood, it's interesting how using a combination of vit K forms can normalize markers of adequacy with much lower doses.


- Vitamin K: the effect on health beyond coagulation – an overview

"Intestinal uptake of K-vitamins is substantially affected by the food matrix in which it is embedded. Vitamin K1, for instance, is tightly bound to the chloroplasts of green vegetables from which it is hardly liberated in the digestive tract. Uptake from cooked spinach and broccoli is 5–10% only, which can double by concomitant fat intake. K2-vitamins, on the other hand, are mainly found in the fat fraction of dairy and are absorbed almost completely (4). From these data it can be understood that, although 90% of our vitamin K intake consists of K1, phylloquinone and menaquinones contribute more or less equally to the human vitamin K status. Also purified forms of vitamin K that may be present in food supplements and functional foods are readily absorbed, especially in combination with a meal (4)."

"K1 and MK-4 typically exhibit half-life times of 1–1.5 hour, long chain menaquinones such as MK-7 and MK-9 are characterized by half life times of several days (4, 6). This was demonstrated in a volunteer experiment in which equal amounts of K1 and MK-7 were ingested; it resulted that K1 had almost completely disappeared after 8 hours, whereas MK-7 (almost exclusively bound to LDL) remained detectable until more than 4 days."​

..but that's for half-life after peak:

- Cees Vermeer - Researching the Gates (another K monster)

Vermeer C. Determination of phylloquinone and menaquinones in food: effect of food matrix on circulating vitamin K concentrations

upload_2019-1-9_9-52-21.png

About 500 mcg of vit K.
Differential lipoprotein transport pathways of K-vitamins in healthy subjects

upload_2019-1-9_9-52-28.png

Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7

upload_2019-1-9_9-52-34.png

- The K-factor in chronic kidney disease: biomarkers of calcification inhibition and beyond

"A theoretical consideration could be the fear that high doses of vitamin K tip the balance towards hypercoagulation; however, because anticoagulant proteins S and C are activated in parallel with the procoagulant factors II, VII, IX and X and because activation in excess of 100% per molecule is physically not possible (by saturation of available γ-carboxylation site), such a scenario can be excluded. For example this is indirectly supported by Vissers et al. [17] documenting no association of vitamin K intake with ischaemic or haemorrhagic stroke in a prospective cohort of more than 35 000 healthy subjects."​

- Thematic Review Series: Fat-Soluble Vitamins: Vitamin K: Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis

"If obfuscation of vitamin K nomenclature is common in the scientific literature, it is rife on the Internet. For example manufacturers and traders of vitamin K2 health supplements often do not reveal whether the product contains MK-4 or MK-7. Why is this important? Apart from the obvious need to fully inform the public, there may be unintended health consequences of ignorance. One important medical issue is that vitamin K supplements may interfere with the stability of anticoagulant therapy in patients taking VKAs such as warfarin. It is known that the agonist effect of vitamin K on VKA anticoagulant therapy is strongly dependent on the chemical form of vitamin K. For example, dose-response studies have revealed that the antidotal potency of MK-7 is much greater than that of K1 (32–34). As a consequence, whereas daily supplements of K1, up to 100 μg, do not normally compromise anticoagulant stability in subjects taking VKAs (32), daily supplements of MK-7 as low as 10–20 μg may rapidly destabilize therapeutic anticoagulant control (34)."​

- Pleiotropic actions of vitamin K: protector of bone health and beyond?

"The beneficial effects of phylloquinone and menaquinone-4 are consistent. Nevertheless, the difference in doses of vitamin K used in the studies, namely 45 mg/d of menaquinone-4 versus 1 mg/d of phylloquinone, raises new questions: (1) What dose of vitamin K supplement is needed to revert subclinical vitamin K deficiency in bone? (2) Can the protective effects of menaquinone-4 (45 mg/d) be accounted for by reversal of subclinical vitamin K deficiency alone? (3) Do as yet-undetermined y-carboxylation–independent mechanisms also contribute to the protective effects of vitamin K, especially menaquinone-4?"

"Considering that dietary vitamin K intake is an order of ~100–400 mcg/d, 45 mg/d of menaquinone-4 appears to be far beyond the level required for reversal of subclinical vitamin K deficiency. Further, administration of phylloquinone (1 mg/d) significantly decreased ucOC [44]. Therefore, 1 mg/d of vitamin K supplement may be sufficient to correct subclinical vitamin K deficiency in bone. Nonetheless, evidence arguing against this presumption also exists. In a randomized, open-label, clinical trial [48], patients with osteoporosis were administered with different doses of menaquinone-4 (15, 45, 90, and 135 mg/d) or vitamin D3 (0.75 mcg/d). As expected, all doses of menaquinone-4 treatment significantly increased urinary excretion of Gla residue, a surrogate marker of total vitamin K–dependent y-carboxylation as compared with vitamin D3. However, urinary Gla excretion was greater in patients who received higher doses of menaquinone-4 (45, 90, and 135 mg/d) than in those who received 15 mg/d of menaquinone-4[.] Undercarboxylated OC was not examined in the study. These observations suggest that oral administration of 15 mg/d of menaquinone-4 may be insufficient to achieve maximal generation of vitamin K–dependent Gla residues in patients with involutional osteoporosis."

"Recently, increasing evidence has suggested that menaquinones, but not phylloquinone, have y-carboxylation–independent functions. Lamma-Carboxylation–independent actions have been proposed to contribute to the protective effects of menaquinone-4 on bone health, although direct in vivo evidence is lacking. Menaquinones function as ligands of “orphan” nuclear receptors, steroid and xenobiotic receptor, and pregnane X receptor, whose ligands and/or functions remain to be determined [49]. Phylloquinone exhibits one order of magnitude lower affinity to these steroid receptors relative to menaquinones, although the effectiveness of phylloquinone and menaquinones on y-carboxylation in vitro is quite similar [50]."

"Another possibility is the antioxidant property of vitamin K [51]. Menaquinones have been proposed to protect neuronal cells from apoptosis by decreasing oxidative stress [52]. Phylloquinone and menaquinone-4 inhibited oxidative stress–induced cell death in oligodendrocyte precursors with EC50 (50% effective concentration) values of 30 and 2 nM, respectively, suggesting that menaquinone-4 is 15-fold more potent than phylloquinone as an antioxidant [52]. An earlier study reported that most phylloquinone is distributed in microsomes in mammalian cells, where y-carboxylation is catalyzed, but that menaquinones are preferentially localized to mitochondria [53]. In bacteria, menaquinones play a critical role in electron transfer in mitochondria and redox signaling, as does ubiquinone [54]. Moreover, a recent study has demonstrated that menaquinone-4 binds to 17-hydroxysteroid dehydrogenase-4 and modulates estrogen metabolism [55]. These findings suggest that menaquinones, but not phylloquinone, may have an additional role, other than y-carboxylation, and that y-carboxylation–independent mechanisms might contribute to the salutary effects of a relatively high dose of menaquinone-4. However, these possibilities have not been explored in vivo in mammals."​

- Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study

"[..]phylloquinone may be converted to menaquinone-4 up to 25% [31–33]."​

- Modern Nutrition in Wealth and Disease (978-1-60547-461-8) - A. Catharine Ross

"The total human body pool of phylloquinone is very small, and turnover is rapid. A peak of circulating phylloquinone concentration following absorption has been shown to be rapidly decreased (half-life 15 minutes), followed by a slower decrease (half-life 2.5 hours) (10). Although the total amount of vitamin K is relatively high, long-chain MKs, rather than phylloquinone, are the major source of the vitamin in liver (2). Data based on liver biopsies of patients fed diets very low in vitamin K before surgery indicate that approximately two thirds of hepatic phylloquinone was lost in 3 days (19). These findings are consistent with a small pool size of phylloquinone that turns over very rapidly. The large amount of MKs in the liver, however, turns over at a much lower rate."

"The major route of ingested phylloquinone excretion is through the feces, and very little unmetabolized vitamin is excreted. Many details of the metabolic transformation of the vitamin are currently lacking, but investigators have shown that the side chains of phylloquinone and MK-4 are shortened to seven or five carbon atoms yielding a carboxylic acid group at the end (14, 20). These 5C and 7C-aglycones, which are the major metabolites of phylloquinone, are excreted in the urine at concentrations that are related to the intake of the vitamin (21). Studies have also shown that glucuronides of menadione are excreted in urine at an amount that is positively related to phylloquinone (22)."

"Substantial amounts of vitamin K in the form of long-chain MKs are known to be present in the human gut. Relatively few of the bacteria that comprise the normal intestinal flora are major producers of MKs. Obligate anaerobes of the Bacteroides (B. fragilis), Eubacterium, Propionibacterium, and Arachnia genera are major producers, however, as are facultatively anaerobic organisms such as Escherichia coli. The amount of vitamin K in the gut can be quite large, and the amounts found in total intestinal tract contents from five patients who underwent colonoscopy ranged from 0.3 to 5.1 mg (23), with MK-9 and MK-10 the major contributors. These amounts are considerably larger than the daily dietary requirement for the vitamin, which is less than 100 g/day. Long-chain MKs, mainly MK-6, MK-7, MK-10, and MK-11, are present at very low levels in plasma, but they have been found in human liver at levels that greatly exceed the phylloquinone concentration (24)."

"A major question remaining is how these very lipophilic compounds that are present as constituents of bacterial membranes are absorbed from the lower bowel. Little evidence on the route of absorption and transport of these vitamins to the liver is available."

"The difficulty in producing a clinically significant deficiency in human subjects, such as an increased prothrombin time (PT) by dietary restriction, and the known rapid turnover of the body phylloquinone pool strongly suggest that MKs do contribute to maintaining adequate vitamin K status (24), but the magnitude of the contribution cannot be determined with the available data."

"The vitamin K–dependent carboxylation reaction does not require adenosine triphosphate, and the energy to drive this carboxylation reaction is derived from the oxidation of the reduced, hydronaphthoquinone, form of vitamin K (vitamin KH2) by O2 to form vitamin K-2,3-epoxide (Fig. 20.3). The lack of a requirement for biotin and studies of the carbon dioxide/bicarbonate (CO2/HCO3-) requirement indicate that CO2 rather than HCO3- is the active species in the carboxylation reaction. Studies of substrate specificity at the vitamin K–binding site of the enzyme have shown that although some differences in biologic activity can be measured, phylloquinone, MK-4, and the predominant intestinal forms of the vitamin, MK-6 and MK-8, are all effective substrates."​

- The Vitamin K Metabolome in Chronic Kidney Disease

"To the best of our knowledge, tissue levels of K1 and MK-4 have not been measured in patients with chronic kidney disease. In a rat model of experimental CKD, significant differences with respect to the concentrations of K vitamins in tissues were observed [21,22]. Significantly lower levels of vitamin K1 were detected in the liver and heart, and higher levels of MK-4 were detected in the kidneys of CKD animals compared with the controls. These differences were evident at 3 weeks of CKD, a timepoint when creatinine and phosphate were only mildly elevated compared with healthy rats, and no vascular calcification was present [21]. Thus, there appears to be an early impact of uremia on vitamin K metabolism in some tissues. The tissue-specific distribution of vitamin K forms in CKD did not differ from that in healthy rats. Although human studies consistently report low serum levels of vitamin K1 in dialysis patients, levels in CKD rats were non-significantly higher than the control rats [21]. The reason for this difference is not clear but indicates possible species-specific factors. To the best of our knowledge, no other study has measured vitamin K1 serum levels in an experimental CKD model."

"There are published and unpublished studies to indicate that the apparent carboxylation defect in hemodialysis patients can be corrected with both vitamin K1 and vitamin K2 supplementation. There was a dose-dependent reduction of various uncarboxylated VKDPs, ucOC, uc-dp-MGP, and PIVKA, with three levels of MK-4 supplementation in a study of German dialysis patients [7]. Similarly, in a small randomized placebo-controlled cross-over study of 20 hemodialysis patients, the provision of 1 mg of vitamin K1 daily normalized PIVKA levels in 100% of hemodialysis patients (unpublished observation). These results are consistent with the one pre-clinical study that demonstrated that vitamin K normalized GGCX ['enzyome involved in the activation of vit K-dependent proteids'] activity [25]."​
 
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LeeLemonoil

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A „downside“ of K1 is that it lacks the testosterogenic properties of the geranylgeraniol side-chain.

Other than that, great info provided here by Amazoniac.
Is there anything known about MK-8 (unique properties) that mk-4 seems to elevate
 

Mossy

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As many have noted on this forum, afters many attempts with supplements, I just can’t find the right balance to make them beneficial. With regard to this thread, I ‘ve been trying K2(mk4) for the last couple of years, but I can now conclude it causes, or brings to life dormant, hemorrhoids. I’ll take the K in the AM, with D3, and white willow bark at bed time. I thought the wwb would counter the hemorrhoid effect, which it did seem to slightly lessen, but it’s still there. I may need to up my dose, but am reluctant to take any for awhile, as I’m still recovering from the last episode—which, for reference, was topical. Oral gives even worse hemorrhoid effects.
 

Soren

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Vitamin K1 is the one with clotting properties, and that's the one you'd want to take with aspirin.

Vitamin K2 has other properties. MK4 is absorbed immediately, while MK7 stays in the liver and is used as needed over a longer period of time.

So vitamin K2 has no clotting properties? I thought they both did.
 

RealNeat

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When people take aspirin (with or without sodium bicarbonate) and K2 (MK4) at the same time, would there not also have to be some dietary fat consumed? Could the omission of this variable account for the mixed results many are reporting? Or am I mistaken and merely taking a K supp at any time (on the same day) the aspirin is taken sufficient as opposed simultaneous consumption?
 

Frankdee20

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Am I overdoing it on the Super K ? It has 1500MCG of K1 per capsule. I take Aspirin daily, and Vitamin E 4 times a week plus some D3. Sometimes I take 2 of them, but not always.
 

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