Vitamin K 2 contributes to bone and cardiovascular health. Therefore, two vitamin K 2 homologues, menaquinone-4 MK-4 and menaquinone-7 MK-7have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health.
However, little is known about the bioavailability of nutritional MK To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects. We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels.
MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues. A number of blood coagulation factors including coagulation factors II prothrombinVII, IX, and X are well-known examples of Gla-containing proteins, which are synthesized in the liver.
Osteocalcin, a bone-specific protein synthesized by osteoblasts, and matrix Gla protein synthesized in blood vessel and bone are Gla-containing proteins synthesized at extra-hepatic sites [ 1 ]. There are two naturally occurring forms of vitamin K: vitamin K 1 phylloquinone derived from green plants and vitamin K 2 menaquinones, MK-nwhich is a series of vitamers with multi-isoprene units at position 3 of the common 2-methyl-1,4-naphthoquinone ring structure.
In food, vitamin K 1 is bound to the chloroplast membrane of leafy green vegetables. MK-4 is found in animal products such as eggs, meat, and liver. MK-4 is derived from the conversion of menadione synthetic analog of vitamin K only consisting of the 2-methyl-1,4-naphthoquinone ring structurewhich is given to the animals. Long chain menaquinones i. The effects of long chain MK-n such as MK-7 on normal blood coagulation is greater and longer lasting than vitamin K 1 and MK-4 [ 3 - 5 ].
The effect of natto derived MK-7 was attributed to its very long half-life in serum, providing a better carboxylation-grade of osteocalcin compared to Vitamin K 1 [ 5 ].
Recent studies revealed that vitamin K 2 contributes to both bone and cardiovascular health [ 6 - 8 ]. Both MK-4 and MK-7 have been used as nutritional ingredients. It has been shown that all vitamin K homologues can be converted to MK-4 in vivo [ 9 - 11 ].
However, only little is known about the bioavailability of the nutritional dose of MK-4 [ 7 ]. In this study, we compared the bioavailability of MK-4 and MK-7 and subsequent changes in serum levels in healthy volunteers. Ten healthy female volunteers age: 20—21 years, mean BMI: Subjects were not allowed to take natto and vitamin supplements other than the experimental versions provided during the study. Informed consent of all volunteers was provided in accordance with the Declaration of Helsinki.
All subjects received the same meals, and the nutrients and energy levels were adjusted according to the Japanese Dietary Reference Intake and National Health and Nutrition Examination Survey. Subsequently, serum MK-4 and MK-7 levels were determined. Pure MK-4 Preparation consisted of dilution into hydrogenated starch hydrolyze powder, which was packed in gelatin capsules.
The capsules were then packed in an aluminum-light-shed bag and kept in a refrigerator until use.We posted a couple of blogs about Vitamin K2 a few years ago. In that blogwe struggled to find a good product to recommend. That got me thinking about what an ideal Vitamin K2 product should look like. I spent a year gathering and reading all the research. And another year finding the right ingredients to make a product based on that research. This product is not intended to diagnose, treat, cure, or prevent any disease.
Based on all of the above, you could make a compelling argument that MK-4 is much more important than MK Our understanding of these various forms of K2 is still in its infancy.
Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women
It may take another generation of research for us to accept that K2 is really K Complex. Like B Complex. Plasma half-life. They keep repeating the fact that MK-7 has a much longer plasma half-life than MK MK-4 is rapidly soaked up by many organs and tissues, so it will be quickly removed from the blood. Does that mean no one has money?
A short plasma half-life his does NOT make MK-4 useless, redundant or any less beneficial to your health. The plasma half life does not make a molecule more or less effective in the body. MK-4 is stored in the brain, pancreas, salivary glands, and arteries. This stored MK-4 cannot be measured and has specific biological activities in these tissues beside Gla-protein formation.
This stored tissue pool of MK-4 may be present much longer. There are no studies that compare the effects of MK-4 to MK If you cruse the interweb seeking knowledge on K2, you will read that MK-4 is synthetic and that MK-7 is natural.
Neither MK-4 nor MK-7, in my opinion, is natural. In my opinion, even K2 made from Natto or Garbanzo chick peas are nature-identical, not natural. Some prenatals have MK-7, which only benefits the mother. Ideally, they all should have MK In a perfect world, you should all be getting K2 from real food. If not for you, certainly for your kids.Hi all, I was wondering if any of you had similar experiences with MK4, and problems determining the correct dosages.
As a quick background, I read Dr Weston Price's book about 15 years ago and of course had a fantastic curiosity as to what, "Activator X" was. As we now know I only found out recently it's K2 in the MK4 form. I have also recently read the Japanese studies that Glakay did with MK4. So I have bought and have been taking MK4 for many of the various benefits I've been taking it going on 6 months now, but here's the problem In fact I was looking for that as an indicator that the MK4 was working.
But about a month later I noticed my teeth were back to normal, and not as slick. By this time I was into my second bottle Carlson's 5mg caps. I figured maybe quality control was suspect, and maybe this bottle was no good.
But I kept taking it but upped my dosage to 20mg per day from It made no difference. I started taking that at 20mg a day, and sure enough, my teeth got slippery again. Great indicator for what must be going on in the rest of my body right?What's A Small Trick You Can Use To Cheat The System? (r/AskReddit - Reddit Stories)
However, a few weeks into it, the same thing happened as when I was taking the Carlson's My question is, have any of you had similar experiences like this, and if so, what did you do or find out about it?
I read that many people eventually lowered their dosages to "maintenance" levels, but wondered how you know it's enough, and whether indicators like slippery teeth remained or dissipated. I have since ordered Complimentary Prescriptions K2 MK4 in the 15mg capsules and will be trying the full 45mg therapeutic daily doses to see what happens with my teeth.
I would also assume that how much vitamin A and D you get daily would have a lot to do with your dosing. I looked around for Vitamin K2 discussions and most are a few years old, so I was wondering what the latest thoughts are on the matter?
Hahaha, yes it sounds rather ridiculous, but MK4 activates the appropriate mechanisms that clear calcium and other minerals found circulating in the blood and tissue where they don't belong, and deposits them where they're supposed go, like bones.
This includes your mouth where you'll find inappropriate calcium and plaque deposits that stick to your teeth.This resource is meant to change that. It begins by teaching you everything you need to know about the vitamin, including its benefits, how much you need, and how to get it from food. It includes shareable infographics to make the concepts fun and easy to understand.
These roles are shown in the shareable infographic below. You can share it using the button in the upper right corner, or the buttons on the bottom strip. You can even use the button in the upper right corner to generate an embed code to share it on your own site if you have one.
This is a role that it shares equally with vitamin K 1. The vitamin K carboxylase is an enzyme that adds carbon dioxide to the side chains of specific glutamate residues within specific vitamin K-dependent proteins. Once added to a glutamate residue, the carbon dioxide becomes a carboxyl group, so the process is known as carboxylation. Carboxyl groups carry negative charges, so carboxylation helps vitamin K-dependent proteins bind to calcium, which carries a positive charge.
In other words, the most well-established role of vitamin K is to add carbon dioxide to proteins and thereby give them the ability to bind calcium. The general structure of an amino acid, featuring a carboxyl group COOH on the right.
At the pH range that prevails within the human body, carboxyl groups often ionize, giving them a negative charge. Although ionic calcium is shown in the figure, some vitamin K-dependent proteins bind to calcium salts rather than calcium ions. However, the role that calcium-binding plays is different for different proteins. We have known about the importance of vitamin K for blood clotting since the s Suttie, Blood clotting is regulated by a variety of proteins known as clotting factors that are all made in the liver and sent out into the blood, where they circulate in inactive form until blood vessel damage makes clotting necessary.
Initially, we only knew that vitamin K was necessary to the function of prothrombin, the precursor to thrombin, which activates fibrinogen to fibrin to form blood clots. We now know that vitamin K is also needed for properly functioning factors VII, IX, and X, which are pro-coagulant proteins involved in the conversion of prothrombin to thrombin.
Vitamin K is just as necessary for the function of proteins S and C, which act as anticoagulants by inactivating other clotting factors that are not dependent on vitamin K, factors V and VIII.
There is a seventh vitamin K-dependent plasma protein, protein Z, that may have additional anticoagulant functions. Thus, vitamin K is required for the proper function of both procoagulants and anticoagulants within the clotting cascade and serves as a raw material necessary for the proper regulation of blood clotting rather than serving as a coagulant or an anticoagulant itself. Vitamin K is necessary for the carboxylation of osteocalcin, a protein produced in bone and also sometimes referred to as bone Gla protein.
Scientists first discovered osteocalcin in the s. Since it was made in bone, most scientists in the field assumed that it played an important role in mineralizing bone or in regulating the turnover of bone mineral or the structural organization of bone.
In the s, however, scientists produced the osteocalcin-knockout mouse, which is genetically modified to lack the gene that codes for osteocalcin. Osteocalcin knockout mice have no obvious defects in any measures of bone health. For three decades, the role of osteocalcin was elusive and the statements made about its function were vague and unconvincing.
Inthings began to change Lee, The scientists who had developed the osteocalcin knockout mouse began more intensively investigating their phenotype and publishing papers about their metabolic and hormonal health. And here, unlike in bone, the effects of osteocalcin are dramatic. Osteocalcin knockout mice are fat, deficient in insulin like type 1 diabeticsinsensitive to insulin like type 2 diabeticsand they have low metabolic rates and high blood sugar.
The males are also infertile and have low testosterone Oury, Surprisingly, all of this is reversed with undercarboxylated osteocalcin rather than fully carboxylated osteocalcin. Undercarboxylated osteocalcin is produced by bone when vitamin K status is inadequate, and its circulation in serum had been interpreted as a sign of vitamin K inadequacy right up through the publication of these papers. In fact, some vitamin K researchers argue that it should still be used in this way, adding controversy to the implications of the osteocalcin knockout mouse studies Booth, During bone resorption, osteoclasts produce acid that decarboxylates osteocalcin and releases it into the serum in its undercarboxylated form ucOCN Ferron, ; Oury, From there, it acts on multiple tissues to improve insulin secretion, insulin sensitivity, blood glucose, the metabolic rate, body composition, and, in males, testosterone production and fertility.
This is illustrated in the figure below.Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study. Eur J Pharmacol. This suggests improved disease activity in RA patients and a promising new agent for RA in combination with standard RA treatment. Practice Implications RA is a chronic inflammatory disease affecting multiple joints.
The progressive destruction of the joints is mainly dependent on the evolution of hyperplastic synovial tissue, which in turn is a function of dysregulated cellular proliferation and apoptosis.
MTX is a standard therapy for RA, and its mechanism of action is thought to be its inhibitory effects on hyperplasia of synovial tissue. In theory, other treatments that inhibit synovial hyperplasia have potential for anti-RA therapy. Menaquinone-7 appears to offer a number of practical benefits over menaquinone-4 in terms of lower dosing and single daily dosing instead of multiple doses. Vitamin K 2 in the form of menaquinone-4 MK-4 has been shown to reduce the proliferation of rheumatoid synovial cells in in vitro and in vivo models.
MK-7 is a form of vitamin K 2 that has greater bioavailability than MK-4 after oral administration, 4 but the therapeutic utility of MK-7 in RA had not been investigated previously. Vitamin K 2 occurs in nature in several forms; each form is designated by the length of the side chain the number of isoprenoid units of this fat-soluble molecule. Different forms of vitamin K 2 are found in varying amounts in foods of disparate origins.
MK-4, a relatively short-chain menaquinone, is found in foods of animal origin, such as butter and egg yolks. Longer-chain menaquinones MK-5 to MK are found in variable amounts in fermented foods, such as cheese. While this dose is very high—and seemingly arbitrary—vitamin K 2 is virtually nontoxic, so this became the standard dose in research and clinical practice.
Research using the MK-7 form of vitamin K 2 began about a decade ago. Likely due to its longer side chain conferring greater liposolubility, MK-7 has a much longer half-life than MK This study was limited by its small size and possible selection bias, which was acknowledged by the authors. However, it confirms the actions previously seen with MK-4 and contributes to the body of knowledge of vitamin K 2 in both commercially available forms as a potentially helpful agent in the management of RA.
No comment was made as to how this finding compares to levels of nonresponse for MK MK-7 appears to offer a number of practical benefits over MK-4 in terms of lower dosing and single daily dosing instead of multiple doses. However, in order to fully understand whether 1 type of vitamin K 2 is in fact superior to another requires more head-to-head studies comparing clinical outcomes of both commonly available forms of the vitamin K 2.
Anti-arthritis effects of vitamin K 2 menaquinone-4 —a new potential therapeutic strategy for rheumatoid arthritis. FEBS J. Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis.
Mod Rheumatol. Clinical results of alendronate monotherapy and combined therapy with menatetrenone VitK 2 in postmenopausal RA patients. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone Rheaume-Bleue K.
Vitamin K 2 and the Calcium Paradox. New York: Harper; Nutr J. Skip to main content. Home October Vol.
Choosing the Right Vitamin K2: Menaquinone-4 vs Menaquinone-7
To clarify the therapeutic role of the menaquinone-7 MK-7 form of vitamin K 2 added to a standard treatment regimen for rheumatoid arthritis RA. RA is a chronic inflammatory disease affecting multiple joints. About the Author.Men in other cultures do extremely well with testosterone rates that the western world considers low. In this newsletter, I want to share two important studies that show Vitamin K2 inhibits estrogen.
K2 MK4 dosing problems - Osteoporosis
K2 caused the inhibition of the amount of estrogen receptor alpha-binding to its target DNA. These results suggest a possible novel role for vitamin K in modulating estrogen function. It is this type of dosage which will tend to lower estrogen levels pretty dramatically in the male body. Booster Bites can get your testosterone higher in seconds I will also send you test results of common male supplements that will shock you to the core — you will want to avoid these supplements!
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Many men suffer poor erection quality and low libido. But men in these other cultures have lots of children, plenty of sex, and live a long time. They also have lower estrogen levels. The real problem for men these days is that they have too much estrogen.
Testosterone supplementation is not addressing the real problem. The real problem is that these men usually have extremely high estrogen levels.Vitamin K is a group of structurally similar, fat-soluble vitamins that include phylloquinone K1menaquinones K2 and menadione K3. In foods MK4 is found in dairy and meats but at levels much smaller than those studied and shown to be helpful in humans.
In contrast, MK7 is produced by bacteria. Humans cannot make MK7.
Vitamin K3 is synthetic and, because of its toxicity, has been banned in by the US Food and Drug Administration for human uses. In contrast to vitamin K3, no known toxicity exists for the vitamin K1 and K2 forms. Vitamin K was first discovered in by Henrik Dam, a Danish scientist. When it was discovered the only known role for vitamin K was an essential factor in blood clotting. But research over the last 40 years has determined that vitamin K is crucial for a lot more than just blood clotting.
Vitamin K is involved in many biochemical pathways. Research shows that specific forms of vitamin K help promote healthy platelet and blood production, grow stronger bones and decrease fractures, reduce markers of inflammation and promotes connective tissue collagen production, making it helpful in tissues throughout the entire body.
While vitamin K1 is preferentially used by the liver as a clotting factor, Vitamin K2 is used in other organs, such as the brain, vasculature, breasts and kidneys. In fact, in the brain vitamin K2 contributes to production of myelin and sphingolipids fats essential for brain health and protects against oxidative damage.
Poor diets and the use of antibiotics may be causing wide-spread vitamin K insufficiency. Low vitamin K status is a known risk factor for osteoporosis.
There are primarily two forms of vitamin K2 commercially available in dietary supplements. These are MK4 and MK7. MK4 used in dietary supplements is a plant-derived, natural product created and purified in a manufacturing facility. MK7 is produced by bacterial fermentation of soy and is created and processed in a manufacturing facility to obtain the MK7 used in dietary supplements.
Both MK4 and MK7 are promoted for bone health. So which is better for bone health?