There is a known paradox that as the body ages there is a tendency for minerals to disappear from bone (osteoporosis) whilst, at the same time, increasing calcification is seen in blood vessels (atherosclerosis). However, in the absence of disease, the blood calcium levels remain remarkably constant despite wide variations in the amount of calcium ingested in both food and drink.
It is vital that the body maintains the concentration of calcium in the blood and ECF (extracellular fluid) within very narrow limits and it is very good at doing this. It has to be good at doing this because vital physiological actions (such as normal nerve conduction and all forms of muscle contraction) depend on the levels being very accurately set. Even quite small changes in blood calcium levels can have serious consequences for the whole nervous system and for the heart.
This finely tuned calcium homeostasis is achieved long-term by an ability to store excess in bone and also to excrete it in urine and faeces. When too little is ingested the opposite happens – excretion is slowed down and the blood level can be restored from the huge quantities stored in bone. Up until about the age of 25 the total amount stored in bone keeps rising. Thereafter this large store gradually falls, particularly in women after the menopause.
Other reasons than simply looking at calcium intake need to be found to explain the “calcium-out-of-bone and calcium-into-blood-vessel paradox”. Some yet unknown linking factor may yet come to light but for now these two contradictory effects would seem to be unrelated and not a paradox at all.
I need to say that I am not a specialist in the highly complex field of mineral metabolism though I used to be a specialist in Intensive Care and had to deal with the clinical consequences when such metabolism goes astray. It must be pointed out that soft tissues, other than blood vessels, can become calcified and that this can happen in both the young and the old. Leaving aside the formation of stones in urine, which can be understood by straightforward chemistry, there are numerous other examples of where calcification occurs in tumours, in bacterial nodules and other areas subject to chronic inflammation or irritation.
It is a straightforward postulate that the actual reason for “hardening of the arteries” is the chronic deposition therein of cholesterol-related plaques damaging the lining of the blood vessels and thence attracting calcification by attachment to adjacent Ca++ ions present in blood and the ECF of the the endothelium (the cellular lining) of the vessels. Also, and somewhat critically, that this will occur regardless of the blood calcium level. Such calcification in soft tissues is almost entirely a one way process with little or no reversal possible – unlike the active processes going on in bone formation and resorption.
Calcification takes place in the inner layer of arteries in the process known as atherosclerosis. The process begins with the production of atheroma. This process, perhaps surprisingly, begins in everyone in childhood and progresses at different rates in different individuals. Low density lipoproteins enter the inner endothelial layer of arteries and so do monocyte cells which then turn into macrophages. These phagocytic cells ingest these lipids. Some of the lipids can be exported to the liver by high density lipoproteins but the phagocytes eventually die and break apart leaving lipids and cell debris behind them. This is thus an inflammatory process and new macrophages then gobble up the mess and the process is repeated. Sequential calcification of these atheromatous plaques completes the process eventually leaving the vessels hard, inflexible, the lumen reduced in diameter and the whole vessel weakened both on the inside and on the outside. Sacs known as aneurysms (which can burst) may form on the outside and internal tears release substances which promote the formation of blood clots or thrombi. It is these thrombi that are the commonest cause of heart attacks and strokes.
Uncrystallised/dissolved calcium in the body fluids exists in two forms. As free chemically active calcium ions (Ca++) and also in another bound form where these cations (positively charged ions) are attached to corresponding (negatively charged) anions. Many of these bound anions will be chloride ions (Cl-) but the majority of bound calcium is tied to plasma proteins such as albumin. These proteins bind to Ca++ ions where they have negatively charged electrons available on their surface. These electronegative spots can also bind to any other available cations such as hydrogen (H+) and magnesium (Mg++) ions, all of which constantly compete with each other to pair up with any available electrons (e-).
It is most important to understand that it is the concentration of the unbound, free, ionised Ca++ ions that plays the critical role in the physiological reactions involving calcium in an organism. Any sudden change in the acid-base status, for example, is just one way of altering the bound to unbound ratio of the Ca++ ions since hydrogen (H+) ions constantly compete for their share of any available electrons. Thus if the blood becomes less acid (fewer H+ ions) some are then freed-up from where they had been bound to proteins in order to compensate for the induced alkalosis. The thus liberated electronegative spots on the proteins can then be occupied by Ca++ ions causing a temporary fall in the free ionised levels of calcium. The resulting lowered ionised calcium levels (clinical hypocalcaemia) can rapidly cause symptoms such as tetany (muscle spasms) despite the fact that the body has enormous stores of calcium, in reserve, in its bone.
There is another closely related element, magnesium, that also plays a vital role in mineral metabolism. In like manner to calcium it dissociates into Mg++ ions and it too contributes to the large store of minerals in bone. Calcium and magnesium play intimately related roles, despite the fact that their clinical and physiological effects are often completely opposite to one another. It may seem surprising that atoms of calcium and magnesium (which are so similar both chemically and in size) can have such different effects. For now a simple approach is to say that when and where calcium levels cause excitement to nerves and muscles, magnesium tends to damp these effects down. Calcium does not exist in high concentrations inside cells, whereas magnesium is found there in significant amounts.
When a lot of people think of bone they imagine a hard, inflexible, dry and rather inert material. Nothing could be further from the truth. Living bone is a dynamic, flexible and metabolic tissue with a large blood supply. The fracture of a just a couple of large bones can lead to the need for a blood transfusion. In its marrow lie cells that are important in the formation of blood and for support of the immune system. When bones are broken they can, with certain limitations, rejoin and remould themselves. Bones are in fact constantly being dissolved and rebuilt. This is brought about respectively by osteoclasts and osteoblasts – two sets of very different specialised cells under hormonal control, which are capable of releasing and fixing calcium. Dissolving bone fairly obviously raises free calcium and rebuilding bone lowers it.
A very simple and classical overview of the hormonal control of calcium metabolism is that parathyroid hormone (PTH) corrects low levels and calcitonin (made in the thyroid) corrects high levels. These effects are mostly mediated by the control of osteoclast and osteoblast activity and by regulating renal excretion and reabsorption.
Vitamin D (or calciferol) in a number of forms plays an important ancillary role particularly where it can promote the absorption of calcium from the gut. Sub-optimal levels of vitamin D are particularly prevalent in the elderly and in northern latitudes or in those not exposed to enough sun. This can lead to a degree of secondary hyperparathyroidism (the release of PTH in response to lowered calcium levels) which in turn accentuates the demineralisation of bone so that blood levels of calcium are restored. A small daily intake of 400 to 800 IU is a straightforward, safe and inexpensive way to minimise this effect, particularly in the elderly. In postmenopausal women and in other conditions where there may be lower than normal levels of oestrogen (or testosterone in men) supplements of vitamin D will have little effect if the body’s levels are already OK but can help offset demineralisation if taken in conjunction with adequate calcium intake.
The complete picture of mineral metabolism is much, much more complicated than outlined so far. The relevant hormones and their co-factors interact in a complex manner. The interplay between calcium, magnesium, the acid-base status and other dissolved particles is equally complex. Low secretion of PTH, as just one example, can have the reverse effect of higher secretion. The fine control of the blood levels of these vital minerals and the mechanisms by which they affect their target cells (both directly and through various channels and gates in the cell membrane) is a very interesting subject but too big to consider right now. Newer research and understanding about this whole area may yet determine important roles for some of the vitamin K groups and a variety of other compounds such as the interleukins (which are involved in the production and control of osteoclasts).
A general overview of the body’s calcium stores is that, in youth and while the skeleton is still developing, a maximal store of calcium phosphate is created and laid down in bone in the form of the mineral hydroxyapatite (a type of calcium phosphate). Those that had a healthy youth and who have a big body frame get off to the best start. Thereafter there is gradual demineralisation of bone in just about everybody. One other noteworthy effect is that bones stay stronger when they bear weight. Being bedridden or being suspended in outer space or having one’s limbs immobilised in plaster are all examples that have detrimental effects on bone density. It is one area where a degree of obesity can actually be beneficial – perhaps this is because of the extra weight-bearing involved.
Suffice it to say that in the absence of disease and in the presence of a “normal” diet one is most unlikely to ever suffer the bad consequences of too much calcium or magnesium in the system. Eating and drinking adequate amounts of calcium and magnesium would actually seem to be sensible and not controversial. Taking small supplements of vitamin D (particularly for those not exposed to much sunlight or who are otherwise at risk of developing osteoporosis) has merit. There is increasing evidence that many (if not most) people do not consume enough magnesium and so perhaps, without overdoing it, regular supplements could have beneficial effects on maintaining not only an improved calcium status but also to give a bit of protection from some of the cardiovascular diseases that plague humanity now at the beginning of the third millennium.
Diet is one thing and it is so often regarded as the first port of call when things in one’s system seem to not be going to plan. For those truly interested in their health I would simply ask that, rather than concentrating on their diets, they concentrated on their whole lifestyle. Both smoking and excessive alcohol intake have a negative effect on bone mineralisation. Smoking puts people at a real risk of heart attack or stroke and a sedentary life will only exacerbate all these problems. I will not lecture others on what they should or should not do so, in return, please don’t lecture me.
I intend to write about my views on “diets” elsewhere but let me also say that I am not a health saint. I have always drunk a certain amount of alcohol and I smoked pretty heavily between the ages of 28 and 55. I was not overweight, not diabetic, my total cholesterol was normal, my blood pressure was normal, I was active on my farm and unstressed mentally and then one night I had a heart attack. I can certainly say that it was a shock and that I was very lucky that it was small and posterior (at the back of the heart) and very rapidly treated with “clot-busters” and a stent. As I lay in the Mater Hospital in Dublin, watching the radiologist doing the angiography and admiring his skill, I was able to see where a plaque of cholesterol had torn the lining of the artery. At that moment I also realised that about the only known risk factor in my life was that I was a smoker. So I determined, there and then, that I would never smoke again. I never did and I was never even tempted to begin.
Others can fool themselves if they want to and (just as I had done many times before) make periodic attempts to stop smoking or simply not care at all. With hindsight I know these two things. The first is to never even be tempted to start smoking – it is as easy (or easier) to become addicted to cigarettes as to heroin and for this the manufacturers and suppliers have to bear a share of the blame. The second point is that when I had tried to stop smoking, on a number of occasions, it was always in a rather “hopeful” way but that when I did finally stop it was because I had made a definite decision to do so. So you can do it if you want to but I believe you will be unlikely to succeed unless you make it your own conscious and definitive decision. A decision no one can take away from you.
I know I have already digressed away from mineral metabolism but while it is still in my mind I would like to add that the reason I started smoking tobacco was actually because I was tempted to try that “harmless” drug marijuana when at university in the 70s. I never became a regular user of the stuff and for me it was never (and was never likely to become) a “gateway” drug to heroin, cocaine, etc but it did lead me very quickly to an addiction to cigarettes. Be warned.