Will Supplements Keep Your Bones Strong?

The most recent 'People's Pharmacy' podcast is worth a listen. The first doctor they interview calls into question the usefulness of meta-analyses, and explains why he believes double-blind placebo controlled studies have been inappropriately applied to nutritional studies.

After the break they have a second doctor on who also discusses the issues with the meta-analysis/JAMA report, and problems with meta-analyses.


https://www.peoplespharmacy.com/2018/10/18/show-1139-will-supplements-keep-your-bones-strong/


"In December 2017, a meta-analysis published in JAMA demonstrated no benefit from vitamin D or calcium supplementation. People taking the supplements were just as likely to break a bone as people taking placebo pills. Those on vitamin D pills were at higher risk for kidney stones, though. To make sense of this research, we talked with two experts: one, a researcher who specialized in studying bone strength and osteoporosis, and the other a leading nutrition scientist. They explain how we can make sense of the confusion. Are placebo-controlled trials the best way to learn about nutritional supplements and their value? How can you tell if your vitamin D levels are low? Are there supplements you might consider to keep your bones strong?"

 

Most doctors don't know that when you are taking Vitamin D3 supplements, you also need to be supplementing with magnesium and K2. Without at least one of those, calcium doesn't get used by bone, but instead gets pushed into the arteries.

 

Unfortunately testing for 25(OH)D is getting harder to get in countries that have gov't run health care.

 

I got diagnosed with osteoporosis nearly 2 years ago and was really worried about it. Admittedly I am 66 and well past menopause, but for someone with ME have been reasonably active. I had taken Vit D for at least 7 years before plus magnesium most of the time. I had also had a couple of blood tests done privately (only cost about £29 in the UK) and had good results each time.

Since then I have added in other supplements including K2 and boron and collagen. I fell downstairs a year ago and landed very hard on my back on the edge of a stair and did not fracture, so hopefully the supplements are helping with the bone quality if not the density.

 

Vitamin K2 plus Vitamin A and D.

Vitamin D creates Matrix GLA protein which K2 activates. But it prevents vascular plaque, not helping bone formation. However preventing future heart attack or stroke is very worthwhile.
Vitamin A creates Osteocalcin which K2 activates which leads to increased bone density.

The research is out there that this works but is at earlier stages then other research due to low funding and the fact this is newer knowledge.

Also 15 minutes of outdoor sunlight exposure if i remember correctly will create 10,000IU of Vitamin D, you can't overdose on sunlight produced Vitamin D and it costs nothing assuming you live somewhere with sunlight. Also the body stores Vitamin D though i forget how long for so supplementation can be avoided entirely if done judiciously. For people with severe ME adequate sunlight exposure may be hard to manage.

 

For older people or people with dark skin, they only produce 1/4 of the Vitamin D of a younger or light skinned person. Also, for anyone living north of Atlanta or LA, between September and April the sun is too high so it is impossible to make any Vitamin D from the sun. For for those of us from Canada or the UK for example, we need to be supplementing during the winter months.

 

You have hit my Achilles Heel. Ouch!

I did a great deal of research a few years ago when my brain was working better and i even have lots of bookmarks to parse but my working memory (if thats what i should be calling it) is shot to hell. I can recall knowledge these days but i can't collate anything (as my psychosomatic thread that i would love to collate). I also can't look over and find references very well unless i remember the exact article. Sometimes what i do is if i remember an exact sentence i can google it in quotes and hunt it down but that works for news articles and often not research papers don't ask me why my brain goes like that, i wish i knew).

So i suggest googling it, Matrix GLA protein and Osteocalcin are Wikipedia articles and i think they mentioned the Vitamin D and A respectively. The K2 activating them may be in its wiki article but other good sources are http://vitamink2.org/ reading through their articles and many citations and posted articles, google scholar, and other websites that i would take with a grain of salt.

Also i wonder if the research study that was testing whether arterial plaque could be reversed with K2 in humans was completed and what the results were, it was running last year as i recall. I don't know if it monitored Vitamin D levels which could throw the results either way.

 

Vit A and D bind to and activate nuclear receptors that in turn act as transcription factors - ie they bind to and regulate the expression of a number of different genes whose products cause the effects we attribute to the vitamins.

There are two types of nuclear receptors activated by vitamin A - RAR (retinoic acid receptor) and RXR (retinoid receptor) which bind the two different forms of active vit A. These functions as RAR-RXR dimers- see here.

Active vit D binds to the vit D nuclear receptor (VDR) which acts as a dimer with RXR. Thus vit A and D work in concert. (RXR also forms heterodimers with thyroid hormone receptors, steroid receptors and others - so vit A is busy)- see here.

Vit D affects bone density by inducing proteins involved in bone remodelling such as osteocalcin, or in intestinal calcium uptake or renal reabsorption - see here.

Vit K2 gets in on the act by activating osteocalcin and matrix GLA protein (MGP), along with several other bone and mineral related proteins (by carboxylating glutamate residues in the protein) - see here. As well as its role in bone formation, osteocalcin acts as a local inhibitor of calcium deposition in soft tissue around bone. Matrix GLA protein plays a similar role in smooth muscle tissue (ie blood vessels). In other words vit K2 plays the ultimate role of keeping calcium in its proper place.

Vit K2 plays many other roles as well (including in blood glucose control, myelination of nerves) - see here and here. There latter link is from a site selling vit K - a product which I take - but it contains good summaries and lots of links to research.

So the fat soluble vitamins A,D and K work and travel together (transported from the gut on chylomicrons and ferried around the body on the surface of LDL and HDL particles from where they are dropped off to cells - vit E travels with them though doesn't have a particular role in bone formation).

Similarly, calcium and magnesium work and often travel together. In general, they tend to have opposite effects and this antagonistic action of magnesium on calcium deposition in soft tissues is particularly pertinent to discussion of calcium supplementation - see here and here.

The faulty logic that claimed that since calcium is necessary for strong bones, high levels of calcium supplementation will help osteoporosis, completely failed to take into account the mechanisms that control ectopic mineralisation. After all, extracellular fluids are supersaturated in calcium and phosphate and without powerful regulatory mechanisms, widespread deposition of calcium phosphate in soft tissues would result.

Magnesium affects other aspects of calcium regulation, such as vit D and parathyroid hormone action - see here - but let's keep things simple.

Finally other minerals, especially boron, impact bone formation. It is a very complicated process. So setting aside the issue of the validity of meta-analyses to assess nutritional supplements, the original topic of the thread, we need to go further back. Vitamins A, K2, magnesium and boron status are all relevant to bone metabolism, not just calcium and vit D. All of these things need to be taken into account when considering supplements to strengthen bone and unaccounted for variability in status of any of these nutrients will confound any analysis.

 

...if they weigh enough, and you pick them up enough, and you don't have ME, quite possibly.

 

@alicec

So, in brain fog digestible terms, that adds up to “Eat more vegetables”?

 

K2 is found in meat that is free range and not factory farmed. The animal's bodies convert K1 from green leafy plants into K2.

 

This would certainly help but may not be sufficient.

Brightly coloured vegetables of all kinds are rich in beta carotene. Efficiency at conversion to vit A varies with individuals so this may or may not be adequate.

Green leafy vegetables are good sources of vit K1, magnesium and calcium, provided they are not loaded with oxalate (like spinach) which makes the minerals unavailable.

Some vit K1 is converted to one form of K2 (MK-4) by us and other animals but it is difficult to get enough K2 simply from K1 since it is preferentially used for blood clotting. As @Alvin said, meat, especially liver, is a good source of MK-4, provided the animals are grass fed. Egg yolk and butter are also good sources - same proviso.

Fermented foods are a good source of another form of K2, MK-7. Cheese is rich, as are things like natto, though the latter is an acquired taste.

Each of the different forms do different things so it is wise to try to get all.

This reference gives a lot of info on vit K content of foods.

It would be difficult to get sufficient magnesium just from leafy vegetables. Other relatively rich sources are nuts and seeds, legumes, oily fish. One source that once provided significant amounts was spring and well water. Now that we have purified our water supply we struggle to get enough and magnesium deficiency is recognised as being widespread. It might be necessary to supplement. Check RBC magnesium. It should be in the upper part of the range.

It is also difficult to get enough calcium this way - hence the recommendation to eat calcium rich dairy.

There's not much boron in green leafy vegetables. Nuts and legumes are rich sources.

 

From what i understand humans don't convert K1 to K2 except in lactating women its done by the breasts (and this K2 is not available for use by the mother). There have been some theories that the bacteria in the gut may do some conversion but from what i recall its not been proven and if it is its not proven to be absorbed by the body (for example some bacteria in the gut can produce B12 but they use it themselves and the human body can't absorb that B12).

 

Wouldn’t it be lovely if we really knew all this stuff?! (It’s like the grains of rice on a chess board how quickly each extra simple piece multiplies complexity).

Argh, I had a second point (question?) but I can’t for the life of me remember.

 

The amount spent on K2 research may be similar or only slightly more then whats been spent on ME research so as a consequence we don't know all that much about it but we have several insights and much unverified research and many unanswered or only partially explored questions. Several of its immune functions/interfaces have been discovered but what they do for us we have not even scratched the surface of yet

Its used anecdotally to remineralize teeth and prevent cavities but last time i checked this has never been tested in a double blind placebo controlled trial. If proven and used wide scale it could cut humanity's need for dentistry dramatically.

It has also been theorized to reduce cancer risk and its immune properties may prevent some types of tumour formation but again the research is in the very early stages and has little to no funding.

Matrix GLA protein which needs K2 to activate it is the most potent agent for preventing vascular plaque known. But whether it can reverse plaque in humans rather then just prevent its formation as it has been proven to do in animals is unknown at present unless the trial i talked about earlier is complete and showed positive results.

As well it reduces bone loss and may reverse osteoporosis but the trials have been mixed but generally positive and need to be replicated in larger cohorts and combined with Vitamin A and D to get actual possible maximized results

 

Humans do make MK-4 using the relatively newly described enzyme UBIAD1. Here is the Uniprot entry for the human enzyme. It is widely expressed in human tissues - see here.
.

 

Interesting but MK4 is found at low levels in many tests done on humans especially vegetarians who presumably eat more vegetables and no meat. Natto and some MK7 containing cheeses being an exception. Also if it were abundantly converted in the human body the studies that found uncarboxylated Matrix GLA protein would not see high uncarboxylated levels in humans with low MK4 dietary intake and would have seen higher level dose related MK4 based on leafy green vegetable intake leading to lower vascular plaque and reduced level of osteoporosis which afaik is not the case. In fact according to an analysis of the Rotterdam study just 10mcg of K2 was enough to reduce heart attack risk iirc, if the human body was creating it its hard to believe people eat less then 10mcg of vegetables containing K1 averaged. A thimbleful of green leafy vegetable should then provide days if not weeks worth of K2...

In summary if all we needed to do was eat green vegetables to get the K2 we need then studies would find the highest K2 levels in people who eat the most vegetables which has never been shown in any study.

That said perhaps we can do some small amount of conversion, one question i have wondered is how do brains in children develop when K2 is required for certain processes to happen and most people consume so little. It could be that we can only convert a very small amount, enough to allow our brains to develop but not enough to do much else. Arterial plaque is a lifelong process and can be found at early stages forming in children's bodies. Certainly worth more research
As an aside K2 in breast milk may also explain why breast fed babies seem to have better outcomes then bottle fed children.

 

expensive stuff it seems, the only source I can find is nearly £1300 for 1mg, oh well, my choppers will have to continue as they are.