Scientists Questioning 

The Excessive Calcium Theory

and my response...

 

 

"The negative correlation between BMD and fracture rate

has been proven a thousand times” 

 

"What little evidence we have in any single racial and ethnic group

 is that low calcium and low vitamin D can increase fractures" 

 

"A 40% reduction in mineral intake 

did not affect age-associated diseases" 

 

"We did not find any bone problems among the milk-drinking swiss" 

 

"I do not agree that a high calcium intake

 leads to an increased activity of osteoblasts (data show opposite)" 

 

"I dont agree that intermittent PTH

enhances fracture risk (opposite is true)" 

 

"The differences among countries

 might be attributed to several other factors" 

 

"Comparing different populations with different genetics

, lifestyle and longevity is not really useful" 

 

"there is no basis for the claim that a high BMD is bad" 

 

"low BMD predisposes to fracture" 

 

"there is no suggestion from the data 

that low calcium in the diet is better than high calcium" 

 

"The body has a unique ability to use the amount of calcium
that it needs for optimal bone strength
and can not absorb the remainder" 
 

"Excess of calcium cannot be stored, ...is simply excreted" 

 

"with advancing age, ability to adapt to low calcium intake largely disappears" 

 

Current very low net calcium absorption rates are proof 

that human prehistoric diet was very high in calcium

 

"The idea that we may “wear out” bone health is certainly a novel one" 

 

"It's not true that an increase in calcium intake will lead to a

proportional increase in osteoblast exposure" 

 

"To link calcium intake to an increase in apoptosis may be taking the argument too far." 

 

"One gets the feeling that you are guiding the literature to

proof your point rather than the other way around" 

 

"...hip fracture incidence is a reflection of 

the socio-economic level and longevity..."

 

"I find this a rather confused set of thoughts" 

 

"Why did you not refer to article (29),(30) and (31)
They do conclude a benefit of calcium

, and their perspectives should have been addressed" 

 

"To age may partially be about a decrease in cell-line viability

and an increase in apoptosis" 

 

 

 

 

 


”The negative correlation between BMD and fracture rate has been proven a thousand times”



Yes, the more calcified, the stronger. And once bone can no longer sufficiently repair microfractures and compose new bone, both BMD and bone strength will decrease, and fracture risk will increase.
However
Young healthy people with relative low BMD have perfectly strong and healthy bones. Young healthy people with low BMD are not at all predisposed to fracture. Low BMD does not cause osteoporosis, but is the result; a symptom.

So, what is the difference between low BMD in osteoporosis and healthy young people?

We know that in elderly high bone turnover rates correlate with low BMD, when osteoblasts can no longer keep up with osteoclasts. 

Opposingly, in healthy young people high BMD correlates with high bone turnover rates (osteoblasts can easily keep up with osteoclasts), and is low BMD not caused by osteoblasts not being able to keep up with osteoclasts, but by low calcium intakes and low bone turnover rates.

Osteoblasts are subject to aging phenomena, and high bone turnover rates may prematurely exhaust osteoblast replicative capacity. Osteoporosis may therefore be prevented by preventing lifetime high bone turnover rates.

In healthy young people low bone turnover rates correlate with low calcium intake and low BMD, which do not predispose them to fracture.

This is supported by the fact that in countries where average BMD is lowest, age adjusted fracture rates are lowest. 

Only in elderly low BMD predisposes to fracture.

In young people low BMD (low bone turnover rates) may save bone formation capacity.

 

 

 

 

 

"In our study (J. Gerontol. 43: B13-B21, 1998) in which the intake of minerals (and not other component of the diet) was restricted, we found that neither longevity nor age-associated disease processes were affected by a 40% reduction in mineral intake"



In experiments, a 40% reduction is far too little.
Within the individual, calcium uptake rates may vary over 4-fold, and internationally, average calcium intake varies up to 3-fold.
Lifetime high calcium intake may prematurely exhaust bone formation capacity through high turnover rates. To test this hypothesis, an experiment is required in which high turnover rates are evoked.
Tests need to be performed in mice to assess the lifetime effects of a very high (3%), high (1.5%), moderate (0.5%), low (0.2%) and very low calcium diet (0.1%) respectively, on eventual bone fracture toughness (over 4-fold variation up and down).

 

 

 


"The differences among countries might be attributed to several other factors. For example, in China people eat high amounts of phyto-oestrogens that may reduce fracture rate" 



International statistics show us that lifetime high calcium intakes at least have no positive effect on fracture rates in old age. And we know that calcium intake has a strong effect on bone metabolism. If other factors would attribute to the differences in fracture rates, these factors would have to dominate and compensate for the effects of calcium.
While the international correlation between lifetime calcium intake, average BMD and fracture rates in elderly is consistent, this, however, is not true for other factors, such as the intake of phyto-estrogens.

Phyto-estrogens are predominantly present in soy. 

Yes, in China relatively much soy is consumed, but in other countries with extremely low age adjusted osteoporosis incidence, such as Congo, Guinea and Togo, hardly any soy is consumed (FAO database). In Japan over 2-fold more soy is consumed (per capita) than in China, but osteoporosis incidence is far higher (and so is calcium intake).

 

Also:

Estrogen is protective for decreasing bone turnover.

Estrogen administration decreased bone turnover in rats, but a 22% soybean protein diet did not (25).

Phyto-oestrogens may replace normal (protective) estrogen. In women consuming 400 mL of soymilk daily during 3 months, estrone and estradiol levels were decreased by 23% and 27%, respectively. (26)

Genisteine is the main phyto-estrogen in soy. Unlike estrogen (estrogen inhibits osteoblast activity; see article), genisteine increases osteoblast activity (27), partly due to increased intestinal calcium absorption (28).

So, the effects of genisteine oppose the effects of estrogen on bone metabolism, while estrogen is known to be protective against osteoporosis.

 

"In the arguments about BMD and hip fracture with different ethnicities, this could also be explained by a number of factors such as differences in bone size and differences in physical activity patterns."

If these factors indeed dominate the influence of BMD, so that there even may be an inverse correlation between lifetime fracture risk and average peak bone mass, shouldn’t we first investigate the lifetime effects of increasing peak bone mass before promoting it as preventive regarding osteoporosis?

 

 

 

 

 

 

 

"Comparing different populations with different genetics, lifestyle and longevity is not really useful"

 

 

Longevity has nothing to do with it, since these fracture rates have been adjusted for age.

And studies (see article) have shown that despite the different genetics, a similar diet eliminates the differences in BMD and fracture risk.

So, only lifestyle remains. 

Physical activity cannot explain lower average BMD in low fracture risk countries.

Calcium intake can. 

 

 

 

 

 

"What little evidence we have in any single racial and ethnic group is that low calcium and low vitamin D can increase fractures"


In elderly, yes, I completely acknowledge this. 
Yes, a low calcium and vitamin D intake generally decreases BMD and bone strength, and therefore increases fracture risk, but in young healthy people these may be (reversable) short term effects, and not significant (if calcium intake is sufficient to accomodate repair of microfractures and to prevent a further decrease in BMD).
My hypothesis acknowledges that there is no cure for osteoporosis. The focus is on prevention, and the key to prevention may lay in finding ways to prevent accelerations in the natural process of 'aging' of the osteoblast replicative capacity. Lifetime low bone turnover rates may proof to offer us protection.

 

In young people low calcium intakes are accompanied by low bone turnover rates. In young people consuming little (but sufficient) calcium may slow down the decrease in the age related osteoblast replicative capacity, and therefore, by lifetime effects, eventually (at old age) be protective regarding fracture risk because more osteoblast capacity remains.

In young people maintaining high BMD is not essential to prevent fractures, whereas keeping bone turnover rates low may be the key to osteoporosis prevention.

In elderly, bone formation capacity may already have decreased, and therefore high bone turnover rates decrease BMD (because bone formation can no longer keep up with bone resorption).

 

In countries with lifetime low bone turnover rates, and therefore low average BMD, due to low calcium intakes, age adjusted fracture rates are low as well.

Low bone turnover rates save bone formation capacity. 


 

 

 

 

 

"We did not find any bone problems among the milk-drinking swiss"


While milk calcium contents are high for humans, they are not for rats and mice.
Mice feedings moderately high in calcium contain about 0.50% calcium.
Cow's milk contains 0.12% calcium (the average human diet contains far less).





"I do not agree that a high calcium intake leads to an increased activity of osteoblasts (data show opposite)"


Yes, calcium supplementation may indeed decrease bone formation in elderly (1)(2)(3) (or have no influence (4)(5)(6)(7)(8), or even increase bone formation (9)), but that is not of importance here.

This theory is about the lifetime effects of calcium intake, not about the effects of calcium once bone metabolism already has been affected by aging.
Bone metabolism is significantly altered due to ageing, and therefore bone metabolism in elderly cannot supply a model for osteoporosis prevention. It is generally accepted that the greatest effects of osteoporosis prevention may be generated from preventative measures during childhood, adolescence and young adulthood until middle age. Therefore, this theory focuses on the influence of calcium on osteoblast metabolism in these age groups. 

* Low calcium intakes through adolescence retard and prolong longitudinal bone growth (10)
* Increased calcium intake is accompanied with increased bone formation rates, correlates with increased BMD, and bone formation and resorption is more or less coupled in healthy young rats (11) and mice (12)
* After calcium depletion, calcium repletion stimulates bone formation rates (but not resorption) and increases BMD in young people (13)(14)(15) and rats (16)(17)

Maintaining high BMD in young people is accompanied with high levels of bone formation (and resorption), in as much as maintaining high muscle volume (bodybuilders) is accompanied with elevated levels of muscle formation and degradation.
In elderly, bone formation capacity has decreased, which has strong effects on bone metabolism response to dietary calcium. In elderly the ARORC (age related osteoblast replicative capacity) has diminished), and therefore less calcium can precipitate on pre-calcified matrix. High calcium intake therefore results in high serum calcium, which inhibits bone resorption, and subsequently bone formation, because of the coupling phenomenon.

Caution regarding bone formation markers
Some of the confusion regarding the influence of calcium on osteoblast activity in young people, rats or mice, may be the result of insufficient accurate measuring methods.
Marker levels may be affected by the rate of clearance (18).
Bone formation markers may contrast (13)(19), and thus not all be equally accurate. 
Serum osteocalcin (SOC) may partly represent inactive osteoblast number rather than osteoblast activity (13) and may be acutely regulated by calcium and/or PTH (20).
Osteocalcin is not only produced by osteoblasts but also released during osteoclastic degradation, may indicate either formation when resorption and formation are coupled or turnover when they are uncoupled. (21)
Changes in SOC and serum alkaline phosphatase may also be the indirect consequences of vitamin D level (22).
Hypocalcemia and parathyroid hormone (PTH) are known to have effects on bone-specific alkaline phosphatase (BSALP) (23), and a significant negative correlation (r = -0.41) was observed between levels of BSALP and the fraction of the tracer that underwent specific binding to bone mineral (24).
C-terminal type I procollagen peptide (PICP) may currently be the most accurate marker of osteoblast acitivity.

 

 

 

 

"I dont agree that intermittent PTH enhances fracture risk (opposite is true)" 


The issue is not short term bone strength and short term fracture risk, but the effects on long term bone health, and thus long term fracture risk. (Just as I dont dispute that extra calcium may stimulate bone formation and decrease short term (shorter than lifetime) fracture risk)
Yes, intermittent PTH may predominantly increase bone formation over resorption, but which one is predominantly increased is not the issue. In this hypothesis not the net effects on BMD are the issue, but the effects on the age related osteoblast replicative capacity, and thus on long term bone health and eventual fracture risk at old age. 

For too long we have been looking at BMD and short term fracture risk without taking into account bone health (ARORC) and eventual fracture risk.

 

 

 

 

 

"I do not agree with you that countries with high BMD also have a high fracture rate...  As far as I know only one paper has really tried to address this in a proper manner. this is the Evos-paper, which showed that the nordic countries had a very low level of BMD compared to southern Europe. (Lunt M, Felsenberg D, Adams J, Benevolenskaya L, Cannata J, Dequeker J et al. Population-based geographic variations in DXA bone density in Europe: The EVOS study. OSTEOPOROSIS.INT. 1997;7:175-89. )." 

This study is about BMD in men and women aged 50-80 years. If BMD in these age groups is lower in the Nordic countries than in southern Europe, this may be due to a greater decrease in ARORC in Scandinavia, which is in line with my hypothesis.

My theory is about the influence of a lifetime high calcium intake, accompanied with elevated BMD levels in healthy young adults (and the average population, but not in elderly), in which the ARORC is far from exhausted.

In the Karlson et al study (36) a random selection of Malmo (Sweden) residents had a higher BMD than in France.


The best comparisons are those between young healthy adults, but average BMD (across all age groups) will also do (adjusted for age).


 

 

 

 

"The problem is the issue of the causal relationship. There are data showing that hip fracture incidence is proportional to the number of books in the public libraries in each country. Thus a reflection of the socio-economic level and of the longevity of the population" 


Longevity has nothing to do with it, since these fracture rates are age adjusted. 
If osteoporosis is the effect of our socio-economic level, what exactly is the cause?
A lack of exercise? A lack of exercise may result in a reversible decrease in BMD, but does not cause exhaustion of osteoblast bone formation capacity. 

Officially promoted osteoporosis prevention is based on the assumption that a high peak bone mass may decrease eventual fracture risk. Data, however, consistently show that in countries where average peak bone mass is significantly higher, age adjusted fracture rates in the elderly are significantly higher as well.
So, at best, increasing peak bone mass has no positive effects.
Shouldn’t we try to find out how this may be possible?
Or should we ignore it because it doesn’t fit in our current beliefs?

 

 

 

 

 

 

Honestly, I don't find it convincing... Why did you not refer to any of the articles attached here? [(29),(30),(31) and (35)] They do conclude a benefit of calcium, and their perspectives should have been addressed

 

Extra calcium is 'beneficial', and helps to strengthen bone until osteoblast replicative capacity is exhausted, in as much as a tan helps to make your skin look young and healthy, until all that sun exposure has made your skin look way too old for your age.

The Heaney article is interesting indeed, because it addresses factors of bone metabolism that actually support my hypothesis. 

 

Heaney (30) argues that there is no such thing as higher BMD than required /  biologically functional. That all the calcium retained in bone is always required. Subsequently, everybody with a not so very high BMD either fails to ingest, or fails to absorb sufficient calcium. 

Heaney assumes that net calcium absorption rate is more or less fixed at a very low level (about 10% at intakes in the range of current recommendations), and that this proves that our human prehistoric diet was very high in calcium.

 

Net calcium absorption rate however, is not fixed at all. It very much depends on, and changes with current dietary habits. The more calcium is consumed, the lower absorption rates, and the lower calcium intake, the higher absorption rates (which both plateau, of course). 

 

In Chinese women consuming little calcium fractional calcium absorption was approximately 61%, and increased to 71% (osteoporotic women), 69% (age-matched control women) and 68% (young women) when dietary calcium was reduced to 300 mg/d.
In contrast, supplementation with 1200 mg Ca resulted in decreased fractional 45Ca absorption. (32)

 

In 11 girls aged 11.6 +/- 2.4 y, "during a low calcium intake, fractional calcium absorption was significantly greater (0.582 +/- 0.087 compared with 0.260 +/- 0.068, P < 0.0001) and urinary calcium excretion was significantly lower (1.30 +/- 0.83 compared with 3.08 +/- 1.98 mmol/d, P < 0.004) than values obtained during a high calcium intake". (33)

 

We therefore must conclude that net calcium absorption rate is not a fixed 'mistake', inhereted from our ancestors, but meant to regulate calcium uptake; to be able to take up the required amount, and to protect us against taking up too much calcium. This is supported by the fact that during space flight intestinal calcium absorption is decreased (34) because at that time there is no need to maintain bone mass.

 

Heaney speculates that "with advancing age, ability to adapt to low calcium intake largely disappears", while however this low absorption rate is a necessity if excessive calcium can no longer sufficiently be temporarily stored in bone, due to a decrease in osteoblast capacity to form new matrix upon which all this calcium can precipitate (subject to the coupling phenomenon). Thus elderly do not have a higher calcium requirement, but absorption rates are low to compensate for the decreased capacity to cope with high calcium intakes.

Assuming that bone mass cannot be manipulated beyond biologically functional, is as assuming that one cannot build muscle mass beyond biologically functional (as if bodybuilders are athletically build instead of overly pumped up).

 

Heaney also assumes that excess calcium "cannot be stored"; is never temporarily stored in our bones, and is always immediately excreted. That bone metabolism and the system that safeguards serum calcium level are only coupled regarding maintaining serum calcium levels sufficiently high, but not to prevent it from increasing too much.

Excessively high serum calcium levels would be lethal, for blocking muscle cell functioning. The system that controls serum calcium level therefore comprises all tools available to up- and downregulate serum calcium levels, including those hormones that co-regulate calcium absorption and excretion. Naturally, maintaining healthy serum calcium levels at all times dominates maintaining biologically functional BMD levels, not just to keep serum calcium levels sufficiently high, but also to keep it prevent from increasing too much. 

When calcium intake is very high, calcium excretion cannot keep up (Heaney: "urine calcium is in itself only weakly regulated"), and the extra calcium is temporarily 'stored' in the bones, until serum calcium levels have sufficiently decreased, and this extra calcium can be gradually excreted.

That is why one can very well manipulate BMD beyond biologically functional levels by keeping calcium intakes high.

Keeping calcium intakes high accelerates the age related decrease in osteoblast replicative capacity, eventually prematurely exhausting bone capacity to maintain BMD and repair microfractures.

 

What Heaney sees as evidence for his conclusions, is actually only evidence for the relationship between calcium intake, BMD and bone strength (until osteoblast replicative capacity has been exhausted). 

Heaney, nor the studies he quotes, never address the effects of lifetime high calcium intake on osteoblast replicative capacity, and thus bone health.

If Heaney's theory was correct, osteoporosis would be synonym to a lack of calcium, and extra calcium would be the cure. We all know that this is not true.

 

Regarding the Brown et al (29) and the Papadimitropoulos et al (31) articles.

I don't dispute that in elderly a low BMD is a key risk factor for fractures, and that a high calcium intake helps to maintain high BMD and momentary bone strenght. 

Brown et al not just conclude that low BMD is a key risk factor for fractures, but that calcium and vitamin D are essential for the prevention of osteoporosis, and essential adjuncts to treatment.

Yes, the short term (up to years) effects of extra calcium may be beneficial regarding momentary bone strength. But what are the lifetime effects of high calcium intake on eventual bone health? Brown et al and Papadimitropoulos et al have not addressed this in their papers, while this is what my theory is about.

Yes, BMD represents momentary bone strength, but not bone health; BMD does not tell us to what extend the age related osteoblast replicative capacity has already decreased; how long bone capacity to fully repair and form new bone will remain; the essence of bone health. 

 

The Peacock article (35) focuses on the short term (4 yr) effects of supplementary calcium and vitamin D on bone strength. Yes, treatment may indeed increase momentary bone strength, but unfortunately, we all know that there still is no cure for osteoporosis. 
We tend to focus on the short term effects of osteoporosis treatments, but we cannot reverse this disease. No treatment can, regardless of the short term effects of treatments on the symptoms of osteoporosis.
So, shouldn’t we instead focus on prevention?
Shouldn’t we first try to understand the lifetime effects of low versus high calcium diets on eventual bone health in elderly? 

The funny thing is that also Peacock thinks that reducing bone turnover in elderly is a good thing. Why wouldn't the same be true for people of all ages, in order to prevent osteoporosis? 

Maybe because in young people you need a low calcium diet to achieve this. 

 

 

 

"The body has a unique ability to use the amount of calcium that is needs for optimal bone strength and can not absorb the remainder" 

The question is: does lifetime maintenance of optimal bone strength come with elevated apoptosis rates?
Does moderate lifetime calcium intake save osteoblast replicative capacity?
And is maintaining optimal bone strength required to prevent fractures in healthy young people?

 

 

 

 

"there is no basis for the claim that a high BMD is bad!"

I don't claim that a high BMD is bad.
I acknowledge (and wrote so) that BMD represents bone strength, and that a lack of capacity to repair and form new bone comes with a low BMD and increased fracture risk.
My theory is about the lifetime effects of elevated bone turnover rates, which, in young people, comes with maintaining high BMD.
This is something very different from claiming that a high BMD is bad.

Opposed to as in young healthy people, in elderly with a decreased osteoblast replicative capacity, high bone turnover rates are generally accompanied with low BMD (osteoclasts being more potent than osteoblasts) and weak bone strength.
In elderly it is beneficial to decrease bone turnover rates (generally increasing BMD because then osteoblasts can keep up with osteoclasts). Doing the same in young people might prevent osteoporosis, while requiring low calcium intakes and leading to a lower average BMD (as is the case in young Asians and Africans). 

 

 

 

"low BMD predisposes to fracture"

 

Yes, but this low BMD is the result (symptom) of decreased osteoblast replicative capacity, not the cause. 
A low BMD in healthy young adults that is the result of low calcium intake does not at all predispose to fracture, but in fact, is protective in the very long term, by saving the age related osteoblast replicative capacity.

In young people low BMD correlates with low bone turnover rates, and lifetime low bone turnover rates might prevent osteoporosis, saving bone formation capacity.

 

 

 

"while there is currently some controversy about how much calcium is required for bone health there is no suggestion from the data that low calcium in the diet is better than high calcium"

 

If we talk about momentary bone strength and fracture risk, no there is not.
If we talk about long term bone health, yes, there is. In all countries with high calcium intakes, fracture rates corrected for age are consistently higher, and vice versa.

 

 

 

 

"I find this a rather confused set of thoughts... It is good to be controversial and thought provoking, but in order to do so one needs a very good appreciation of the published literature"

 

My hypothesis is not the result of compiling other's conclusions, but of combining 'small' facts that have emerged from published literature with different conclusions than mine. 

Proper investigation requires gathering facts, not conclusions.


Fact 1: Osteoporosis may be the result of premature exhaustion of the capacity to form new bone matrix. 
Fact 2: Osteoblasts create this matrix.
Fact 3: Like all other cells in our body, osteoblasts are subject to aging phenomena
Fact 4: High bone turnover rates accelerate osteoblast replication rates.
Fact 5: In healthy young people (not in elderly), maintaining high BMD comes with high bone turnover rates.
Fact 6: The key to osteoporosis prevention may lay in the lifetime prevention of high bone turnover rates (accomplished by low calcium intakes in healthy young people). 

 

 

 

 

 

 

 

"The idea that we may “wear out” bone health is certainly a novel one."

What is not novel, is that bone health largely depends on bone capacity to repair and form new bone, which heavily depends on osteoblasts.
Studies have shown that osteoblasts are subject to aging phenomena.
Studies have also shown that in osteoporosis there is a lack of osteoblast capacity. Osteoporosis is strongly age-related, and aging in general is about a decrease in the replicative capacity of cells (shortening of telomeres).
So, though combining all the above may be novel, this is not true for the separate components.

 

 

 

 

"One of the fundamental hypotheses in the argument here is that an increase in calcium intake will lead to a proportional increase in osteoblast exposure, which is likely untrue."

Proportional? I never said that.
To what extend elevated rates are proportional to increased calcium intakes is irrelevant.
The question is: do higher calcium intakes come with elevated apoptosis rates?


 

 

"To link calcium intake to an increase in apoptosis or to exhaustive age-related osteoblast replicative capacity may be taking the argument too far."

Studies have shown that calcium intake and osteoblast activity are related.
Studies also show that osteoblast activity and apoptosis rates are related.
Thus, calcium intake and osteoblast apoptosis rates are indirectly related. Apoptosis rates determine the speed of the decrease in osteoblast replicative capacity.
Is it taking too far to combine what is already known?

 

 

 

 

 

 

"One gets the feeling that you are guiding the literature to proof your point rather than the other way around."

Creating a new theory is about finding support for all its components. 
It’s about discovering a pattern in the known facts, and not about following the conclusions / perceptions of others.

 

 

 

 

 

 

 

"I think that the decline in bone strength with age is a multifactorial one and that perhaps a decrease in cell-line viability and an increase in apoptosis is partially to blame. Certainly these things are all about what it is to age."

Thus, the question is: what events are related to elevated apoptosis rates, right?

 

 



 



 


 

 

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