This Protein Can Affect How Much Vitamin K2 You Need

Nutrition / Research / Vitamin K2 / August 19, 2015

Take Calcium With Breakfast to Increase Your Fat Burn

Lara Pizzorno is the author of “Your Bones: How You Can Prevent Osteoporosis and Have Strong Bones for Life – Naturally” and a member of the American Medical Writers Association with 29 years of experience specializing in bone health.

Recently we asked Lara if she would help us provide a series of short, ongoing videos to help you (our customers and readers) stay up to date on the latest facts and science related to bone health and overcoming osteoporosis naturally.

In this latest video, Lara discusses how this one protein can affect how much vitamin K2 you need and which form is best for you. Watch the video below (or read the transcript provided) and let us know what you think in the comments. 🙂

Hello, my name’s Lara Pizzorno. I am the author of “Your Bones” and I’m here to share information with you that I hope can help you to have healthier bones.

In this video we’re going to talk about:

ApolipoproteinE or APOE for short, and how single nucleotide polymorphisms or SNPS in the gene for APOE can affect how much Vitamin K2 you need and what form of Vitamin K2 might serve you best.

So what’s ApolipoproteinE or APOE for short?

APOE is a protein that binds to Lipo, that’s why it’s APO Lipo. Which means fat containing proteins like cholesterol and the fat soluble vitamins, which include Vitamin K along with Vitamin D, A, and E. So that these fat soluble or fat containing compounds can be carried throughout our body in the bloodstream. As you probably know, fat and water don’t mix well so fat containing compounds, like cholesterol and the fat soluble vitamins, which include Vitamin K need help to move through our blood which is primarily made of water and this is the primary job of APOE.

So here is the bottom line for APOE. It comes in three flavors or SNPS. Three SNPS, APOE2, APOE3, and APOE4. Around 7% of us have inherited the APOE2 SNP. Most of us, about 78% of us, carry the SNP for APOE3, and about 14% of us have inherited the SNP for APOE4.

If you are among the 14% whose genetic inheritance includes a SNP for APOE4, you will remove Vitamin K rich lipoproteins from your bloodstream more quickly than the average person.

Because of this, you are going to need more K2 than the average person.

You will definitely want to be taking Vitamin K2 in the form of MK7. And you may need greater doses than the 120 micrograms per day which is the dose recommended for the average person. On the other hand, if you are among the 7% of us who have inherited the APOE2 SNP, you’re going to clear Vitamin K rich lipoproteins, and therefore Vitamin K2, more slowly than the average person. If you take the average amount of MK7, it may accumulate to greater levels in your body and in your brain, promote energy production so effectively in your brain that you have trouble sleeping.

Very few of us carry the APOE2 SNP, only about 7% of us. But if you’re one of them which you may suspect if neither atherosclerosis nor Alzheimer’s disease runs in your family. Which is a happy result of the protected anti-inflammatory effects of this APOE2 SNP, then you are among the few who are going to retain Vitamin K far longer than the average person. So you may find that taking MK7 every day doesn’t agree with you. In this case, you could try only taking your MK7 supplement every third day or so. Or supplementing with MK4 instead.

Most of us, 78% of us, carry the APOE3 SNP.

So we clear our Vitamin K2 delivering cholesterol neither too quickly nor too slowly and will do best with MK7. It’s easy to find out which form of APOE you have. Your doctor can run a blood test that will tell you. Or you can order one for yourself online, and I provided a link to one of the labs that offers this test.

In our next video we’re going to talk about another single nucleotide polymorphism that can make a big difference in how much Vitamin K2 you need. This is a SNP in the enzyme that recycles Vitamin K for reuse in our bodies, and it is an enzyme called Vitamin K epoxide reductase or VKOR for short. It’s a little easier to say and remember.

I hope this one has been interesting for you and that you will tune in to learn about VKOR and how it might affect your Vitamin K needs. Thanks for tuning in. Bye.


Sources:

Phillips MC. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014 Sep;66(9):616-23. doi: 10.1002/iub.1314. PMID: 25328986

http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=900575&labCode=AMD

Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012 Mar 1;3(2):182-95. doi: 10.3945/an.111.001800. PMID: 22516726

Pilkey RM, Morton AR, Boffa MB, et al.  Subclinical vitamin K deficiency in hemodialysis patients. Am J Kidney Dis. 2007 Mar;49(3):432-9. PMID: 17336705

Kaneki M. [Genomic approaches to bone and joint diseases. New insights into molecular mechanisms underlying protective effects of vitamin K on bone health].[Article in Japanese]Clin Calcium. 2008 Feb;18(2):224-32. doi: CliCa0802224232. PMID: 18245893

Jeenduang N, Porntadavity S, Wanmasae S. Combined PCSK9 and APOE Polymorphisms are Genetic Risk Factors Associated with Elevated Plasma Lipid Levels in a Thai Population. Lipids. 2015 Jun;50(6):543-53. doi: 10.1007/s11745-015-4017-9. Epub 2015 Apr 22. PMID: 25899039

Kohnke H, Sörlin K, Granath G, Wadelius M. Warfarin dose related to apolipoprotein E (APOE) genotype. Eur J Clin Pharmacol. 2005 Jul;61(5-6):381-8. Epub 2005 Jun 11. PMID: 15952022

 

Comments
Sylvia Onusic, PhD, CNS, LDN
Sylvia Onusic, PhD, CNS, LDN

I was looking for your references for your statements that APOE-4 ‘s need to take MK-7. APOE-4’s remove vitamin K2 from the circulation quicker so would this not also apply to MK-7?

I read many bloggers say that MK-7 has a longer half-life- but all the research says is that it stays in the circulation longer. This could mean it is not being absorbed, not that it has a longer- half-life. What do you think?

Please contact me personally at sylvia @drsylviaonusic.com. I would kindly like to discuss this topic with you. I am researching a project on MK-7 vs MK-4 utilization.

Thanks.

Lara Pizzorno
Lara Pizzorno

Hi Sylvia,

Great questions! Thanks so much for writing in to me.

Yes, absolutely, carriers of APOE4 are likely to require more vitamin K2 than the “average” person.
Yes, APOE4 carriers remove K2 more rapidly, but MK-4, at best, is present in the bloodstream for only 6-8 hours, while MK-7 remains available for ~ 3 days. Even if MK-7 is removed more rapidly, it will still be present far longer than MK-4, and increasing the dosage of MK-7 will also help ensure it remains available for APOE4 carriers for far longer than MK-4.

The fact that MK-7 is in the bloodstream indicates that has been absorbed from the digestive tract. The fact that MK-7 has been found to be far more effective than MK-4 at lowering levels of unOC and unMGP (i.e., in carboxylating or activating osteocalcin and matrix Gla protein) indicates that it is being utilized.
All of us, not just individuals carrying APOE4 require K2 – preferably in supplemental form as MK-7 unless we are regularly consuming natto.

I am basing my remarks about APOE4 carriers being likely to require more K2 than the “average” person on the fact that individuals carrying this SNP clear vitamin K far more rapidly than “average”. Little research has been done investigating the impact of this fact on K2, although APOE4 is well known to increase risk for conditions in which dysfunctional calcium handling is a significant component. Here are a couple of recently published papers: Tudorache IF, Trusca VG, Gafencu AV. Apolipoprotein E – A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features. Comput Struct Biotechnol J. 2017 Jun 6;15:359-365. doi: 10.1016/j.csbj.2017.05.003. eCollection 2017. PMID: 28660014. Xu M, Zhao J, Zhang Y, et al. Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis. Biomed Res Int. 2016;2016:3912175. Epub 2016 Oct 27. PMID: 27868062.

The most recently published paper on the relationship between APOE4 and vitamin K (research reported in 2011, Apalset EM, Gjesdal CG, Eide GE, et al. Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study. Bone. 2011 Nov;49(5):990-5. doi: 10.1016/j.bone.2011.07.035. Epub 2011 Aug 2. PMID: 21839190) only included dietary consumption of vitamin K in a Norwegian population, and found a protective effect for K1; however, as you know, the amount of K2 (not just MK-4 but especially the long chain menaquinones, which include MK-7) provided by the Western diet is far too low to exert significant beneficial impact (which is why supplemental K2/MK-7 is now being recommended and a number of studies have recently been conducted in Norway confirming MK-7s beneficial effects on cardiovascular disease and osteoporosis).
The research looking at differences in vitamin K intake has been focused on warfarin – i.e., on the need for warfarin dosages to be determined and adjusted in relation to how rapidly an individual clears vitamin K, which is significantly impacted by APOE status. Here are a few of papers related to this issue that may be of help to you:
Kaneki M. [Genomic approaches to bone and joint diseases. New insights into molecular mechanisms underlying protective effects of vitamin K on bone health].[Article in Japanese]Clin Calcium. 2008 Feb;18(2):224-32. doi: CliCa0802224232. PMID: 18245893
Jeenduang N, Porntadavity S, Wanmasae S. Combined PCSK9 and APOE Polymorphisms are Genetic Risk Factors Associated with Elevated Plasma Lipid Levels in a Thai Population. Lipids. 2015 Jun;50(6):543-53. doi: 10.1007/s11745-015-4017-9. Epub 2015 Apr 22. PMID: 25899039
Kohnke H, Sörlin K, Granath G, Wadelius M. Warfarin dose related to apolipoprotein E (APOE) genotype. Eur J Clin Pharmacol. 2005 Jul;61(5-6):381-8. Epub 2005 Jun 11. PMID: 15952022

Please keep me posted on your progress with your project re MK-7 vs MK-4 utilization. A final thought: you might also consider contacting Schurgers and Vermeer, the two vitamin K researchers who, in my opinion, are by far the leaders in the field. When I have had questions for them, I have done so and have been astounded by their gracious willingness to reply to me.

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