Saturday, April 27, 2013

Recent rambling investigations

I spent some time recently investigating Vitamin K2 & Osteocalcin.

1st, there are apparently 2 forms of Osteocalcin -- undercarboxylated Osteocalcin (ucOC) & gamma-carboxylated Osteocalcin. Which one is good? Which one is bad? What do we want? It gets complicated.

At 1st glance, it looks like ucOC is good:

Change in Undercarboxylated Osteocalcin Is Associated with Changes in Body Weight, Fat Mass, and Adiponectin: Parathyroid Hormone (1-84) or Alendronate Therapy in Postmenopausal Women with Osteoporosis (the PaTH Study)

I keep forgetting to always keep in mind which population the study was conducted in. I'm not a post-menopausal woman with Osteoporosis, so the findings of this might not apply to me well or at all.

Anyway, in short they found:

↑ ucOC --> ↑ Adiponectin; ↓ Body weight & ↓ Fat

In the study women given PTH (Parathyroid hormone) saw increased levels of ucOC & women given Bisphosphonates saw decreased ucOC. This was interesting to me since a lot of patients take Bisphosphonates & I was unaware of the potential negative effects on body composition they might have.

Moving on, here's another study that makes ucOC look good:

Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus.

Again, mind the population. I don't have T2DM (Type 2 diabetes mellitus) & I hope I never will.


↑ ucOC --> ↑ Free testosterone (note: this is not a causal relationship, just an association)

So far this sounds quite good from a body composition standpoint. Who doesn't want to lose weight, lose fat, & increase free testosterone?

The bad news came in this study:

Vitamin K supplementation reduces serum concentrations of under-γ-carboxylated osteocalcin in healthy young and elderly adults

Here the authors write:

↑ ucOC --> ↑ Fracture risk;  ↓ BMD (Bone mineral density) (note: also an association)

They knew that there is an association between Vitamin K insufficiency & elevated ucOC:

 ↓ VitK --> ucOC

They wanted to see if supplementing Vitamin K (in this case K1 AKA Phylloquinone) would lower ucOC levels & it did. The idea here being:

 ↑ VitK --> ↓ ucOC --> ↓ Fracture risk; ↑ BMD

So it seems ucOC is not clear-cut. We may want higher levels from a body composition standpoint, but lower levels from a bone health standpoint. I'm a young male, so you might think bone health should be low on my list of priorities, but I came across an interesting fact the other day that up to 25% of men will suffer a Fracture due to Osteoporosis during their lifetime -- 1 in 4, not terribly good odds.

Keeping with the beneficial effects of Vitamin K on bone health, I found this:

Treatment with vitamin D3 and/or vitamin K2 for postmenopausal osteoporosis.

The authors state:

[T]reatment with 1alpha-hydroxyvitamin D3 (alfacalcidol) slightly reduces bone turnover, sustains lumbar bone mineral density (BMD), and prevents osteoporotic vertebral fractures in postmenopausal women with osteoporosis, while vitamin K2 (menatetrenone) enhances gamma-carboxylation of bone glutamic acid residues and secretion of osteocalcin, sustains lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis.
 They go on:

Available evidence suggests that the effect of vitamin K2 on mineralization by human periosteal osteoblasts is enhanced in the presence of 1,25 dihydroxyvitamin D3 in vitro. The effect of vitamin K2 on BMD in ovariectomized rats is affected by the plasma 25-hydroxyvitamin D3 level in vivo, and is significant only when rats are fed a diet containing vitamin D3. Based on this line of evidence, combined treatment with alfacalcidol and menatetrenone for osteoporosis is surmised to be more effective than treatment with menatetrenone alone, and may have anabolic effects on osteoporotic bone.
In short, Vitamin D3 & Vitamin K2 are both good for bone health & potentiate the effects of one another.

One last pro-bone health study, just to be thorough:

Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

This study was interesting to me because it pointed out the difference between BMD (Bone mineral density) & BMC (Bone mineral content). Looking at BMD alone may not provide enough information because:

Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent [positive] contribution to bone strength and fracture risk. 
In conclusion, although I am not a post-menopausal woman with Osteoporosis, bone health does sound appealing to me & I believe there are other benefits to supplementing Vitamin K2 as well. Plus, I love natto (纳豆). While Vitamin K2 might decrease ucOC levels which might have negative effects on body composition, I am not too sure about the strength of this correlation & where it stands compared to other factors such as overall diet, activity level, etc. I imagine the effect is not too large since my body composition is quite good despite regular intake of large amounts of this delicious fermented food product.