“Treatment with vitamin K, especially MK-7, effective enough to reduce bone resorption,” say researchers reporting the results of a landmark study published April 2012 in Calcified Tissue International, a leading journal for research on the structure and function of bone. 
This one year-long study compared the effects of vitamin K1 to those of vitamin K2 (as MK-7) on a number of markers of bone resorption (breakdown) and formation in 173 postmenopausal women.
The women were randomly divided into four groups:
- A group of 38 women given 800 mg of calcium and 400 IU of vitamin D3 per day (called the CaD group )
- A group of 38 women given 800 mg of calcium, 400 IU of vitamin D3, and 100 mcg vitamin K1 per day (the CaDK1 group)
- A group of 39 women given 800 mg of calcium, 400IU of vitamin D3, and 100 mcg K2 as MK-7 per day (the CaDK2 group)
- A control group of 58 women (CG)
The first three groups received their supplements via milk and yogurt that had been fortified. No dietary intervention was delivered to the control group; the women just continued with their usual diet.
Blood levels of 25(OH)D increased significantly in both the CaDK1 and CaDK2 groups, but more in the CaDK2 group.
25(OH)D is the form of vitamin D circulating in the bloodstream and the most reliable indicator of body stores. By the end of the study, both groups given vitamin K averaged much greater levels of vitamin D than the group given only calcium and vitamin D (CaD) or the control group.
However, in the group receiving vitamin K as K2/MK-7, blood levels of vitamin D were more than 30% higher than in the group receiving vitamin K1.The change in vitamin D levels was -0.7 in the control group, +1.6 in the CaD group, +2.5 in the CaDK1 group, and +3.6 in the CaDK2 group.
Blood levels of IGF-I increased significantly only in the CaDK2 group.
IGF-1 is an anabolic (tissue building) hormone-like peptide. Recent studies show IGF-1 stimulates bone formation in postmenopausal women, primarily by signaling the precursor cells for osteoblasts to mature and become active. Blood levels of IGF-1 were -6.5 in the control group, +5.8 in the CaD group, +5.9 in the CaDK1 group – and a whopping +11.9 in the CaDK2 group.
Blood levels of UnOC (uncarboxylated osteocalcin) dropped in CaDK1 and CaDK2 groups, but CaDK2 had almost double the drop in UnOC.
UnOC is the inactive form of osteocalcin, which is unable to deposit calcium in bone. Vitamin K2 is responsible for activating osteocalcin, so high levels of unOC mean not enough K2 is around to get this job done. Both the CaDK1 and CaDK2 groups had much lower levels at follow-up compared to the CaD and CG groups, but in the CaDK2 group, which was given MK-7, the drop in UnOC was -23.6, almost double the -13.3 drop seen in the CaDK1 group, which was given K1!
Urine levels of the bone breakdown byproduct deoxypyridinoline (D-Pyr) dropped in CaDK1 and CaDK2 groups, but the drop in CaDK2 was triple that seen in CaDK1.
Osteoclasts’ activity leads to the release of bone breakdown products, including pyridinium cross-links, such as deoxypyridinoline (D-Pyr). This is what the Pyrilinks-D urine test for bone loss measures. High levels of D-Pyr indicate excessive osteoclast activity and thus, excessive bone loss. Lower levels show the opposite – less osteoclast activity, less bone removal.
Women in the CaDK1 group experienced an average -3.4 drop in D-Pyr. In women in the CaDK2 group, the average drop in D-Pyr was almost three times greater: -9.6!
Both forms of vitamin K exerted beneficial effects on the RANKL/OPG ratio.
What’s the RANKL/OPG ratio?
As explained in more detail in my blog sharing new findings on why soy foods can help prevent bone loss, (link to blog: http://www.algaecal.com/bone-health-news/latest-research-shows-soy-foods-help-prevent-bone-loss/ ) RANKL is a cellular messenger, which sets off a series of events that results in the production of osteoclasts ready to remove old bone, while OPG shuts down this process.
When RANKL binds to a cellular receptor called RANK, this turns on nuclear factor-kappaB (NFkappaB), a seriously pro-inflammatory messenger. NFkappaB sets off the production of a whole bunch of inflammatory molecules—one of which is osteoclasts. You may remember we’ve said that anything that promotes chronic inflammation promotes bone loss. RANKL’s activation of NKkappaB, which in turn activates osteoclasts, is behind this connection.
If we want to keep our bones, we must keep RANKL under control. But we cannot afford to totally eliminate RANKL because RANKL’s binding to RANK is also necessary for the activation of immune cells (our T and B cells, specifically). Without a well-functioning immune system, we’re prey to infections and cancer. What good are great bones if we’re dead? (More on this in the discussion of why you do not want to take denosumab—link to blog– http://www.algaecal.com/bone-health-news/denosumab-aka-prolia-xgeva-even-worse-than-the-bisphosphonates/ )
So, how do we tune down RANKL safely? We send in its decoy receptor osteoprotegerin (OPG), which also binds with RANKL, and thus blocks the interaction between RANKL and RANK, and the activation of NFkappaB. Pretty nifty how our body has worked out a way to naturally balance all this for us, isn’t it? You can think of RANKL as a Conan, the Barbarian, type of cellular messenger, and see OPG as an acronym for “Oh, Pretty Girl!” Enough OPG around and RANKL will be distracted and forget about binding to RANK. A key point here is that RANKL is just tuned down, not eliminated (so our immune cells will still mature).
So, what dating service encourages this happy meeting of RANKL and OPG? You guessed it – vitamin K! (And, as explained in http://www.algaecal.com/Blog/latest-research-shows-soy-foods-help-prevent-bone-loss/11483 , so does soy, specifically, a bioactive isoflavone compound in whole soyfoods called genistein, which is well known to lessen inflammation. Now we know genistein is doing so by increasing OPG and decreasing RANKL. 
The study we’re discussing here also showed that both vitamin K1, and K2 as MK-7, impact RANKL and OPG. Both forms of vitamin K affect both of these cellular receptors, but vitamin K1 lowers RANKL more than K2/MK-7, while K2/MK-7 increases OPG more than K1.
What does all this mean for YOUR BONES?
Now you have yet another reason to eat plenty of leafy greens, which are loaded with vitamin K1, as well as to take a supplement providing vitamin K2 (MK-7).
 Kanellakis S, Moschonis G, Tenta R, et al. Changes in Parameters of Bone Metabolism in Postmenopausal Women Following a 12-Month Intervention Period Using Dairy Products Enriched with Calcium, Vitamin D, and Phylloquinone (Vitamin K(1)) or Menaquinone-7 (Vitamin K (2)): The Postmenopausal Health Study II. Calcif Tissue Int. 2012 Apr;90(4):251-62. Epub 2012 Mar 4. PMID: 22392526
 Marini H, Minutoli L, Polito F, et al. OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration. J Bone Miner Res. 2008 May;23(5):715-20. PMID: 18433304
This article was written by Lara Pizzorno, author of “Your Bones”
|Lara Pizzorno is a member of the American Medical Writers Association with 26+ years of experience writing for physicians and the public, am Editor of Longevity Medicine Review as well as Senior Medical Editor for SaluGenecists, Inc.More about Lara Pizzorno|