JOURNAL OF APPLIED NUTRITION, VOLUME 34, NUMBER 2, 1982
THE CALCIUM CONTROVERSY
Guy E. Abraham, M.D.
It is often stated that large amounts of calcium are required for strong bones, to calm
nerves and for other characteristics of good health. Some nutritionists recommend up
to three grams of calcium a day to prevent calcium deficiency. The purpose of
this editorial is to review some aspects ofHuman Evolution, Physiology, Biochemistry
and Dietary Habits in order to clarity calcium requirements and its close relationship
to intake of other nutrients, mainly magnesium,
EVOLUTIONARY CONSIDERATIONS
Over the past 6000 years or more man evolved in a magnesium and potassium-rich,
but calcium and sodium-poor, environment. For survival, the human body had to
develop efficient conserving mechanisms for sodium and calcium To conserve
sodium, the Zona Glomerulosa of the Adrenal Cortex secretes a veiy potent
mineralocorticoid, Aldosterone, which increases sodium retention via the kidney11.
To conserve calcium, the skin developed a synthetic process that manufactures
Vitamin D3 from a cholesterol derivative, under the influence of solar
ultraviolet radiation. Vitamin D3 is then hydroxylated by the liver to 25-OH-D3. The kidney
is the site ofthe most important step: 1-hydroxylation of25-OH-D3 to generate 1,
25 (OH)2 D3, the most potent calcium-conserving substance16. It
increases calcium and phosphate absorption in the small intestine and decreases calcium excretion in
the urine:
PHYSIOLOGICAL CONSIDERATIONS
The 1-hydroxylase is located in the kidney as a mitochondrial enzyme. It is sensitive
to intramitochondrial calcium and phosphate. Intromitochondrial accumulation of both calcium and phosphate depress the activity of 1-hydroxylase, thereby decreasing formation of 1, 25 (OH)2 D322.A low phosphate diet increases and a
high phosphate diet depresses 1, 25 (OH)2 D3 production20.
Besides 1, 25 (OH)2 D3, there are two hormones that play an important role in
calcium metabolism: Calcitonin (CT) and Parathyroid Hormone (PTH)3. Both
hormones are sensitive to serum ionized calcium levels. An increase in serum
ionized calcium results in stimulation ofCT secretion and suppression of PTH secretion.
CT and PTH regulate skeletal turnover of calcium and availability of cytoplasmic
calcium3. The major skeletal effect ofPTH is to increase bone resorption by
stimulating osteoclasts, thereby increasing mobilization of calcium from bone.
PTH also iavors cellular uptake of calcium by soft tissues and phosphate excretion
by the kidney. CT has the opposite effect, that is, it increases deposition of calcium
in the bone matrix and blocks cellular uptake of calcium by soft tissues. Magnesium
suppresses PTH and stimulates CT secretion28, therefore favoring deposition of
calcium in the bone and removal of calcium from soft tissues. Furthermore magnesium enhances calcium absorption and retention ' ,
whereas increasing calcium intake suppresses magnesium absorption2,25.
BIOCHEMICAL CONSIDERATIONS
Calcium and magnesium are often antagonistic in their
effect ofbiological reactions7. For example, the biosynthesis ofboth phospholipids and proteins involve
enzymatic steps which have an obligatory requirement for magnesium and are
calcium-inhibited. The glycolytic pathway contains five enzymatic reactions that have an absolute
requirement for magnesium and require optimal magnesium/calcium ratio for peak
performance.
In order for the cell to maintain the proper magnesium/calcium ratio, several levels of
regulation are available, acting on the removal of calcium from the cytoplasm One
such mechanism is the ATP-dependant calcium pump in the cell membrane 9'10. The
other important mechanism is the transport of calcium inside the mitochondria. The
mitochondria uptake of calcium is reversible if calcium concentrations in the
micro environment are kept below certain limits. Above these limits,
calcification of mitochondria occurs with subsequent cellular death. In the presence of
magnesium, the uptake of calcium by mitochondria can be slowed down. Since ATP utilization
is magnesium-dependent, it becomes obvious that the calcium pump at the cell
membrane is also magnesium-dependent. The generation of ATP itself through the
glycolytic pathway is in part magnesium-dependent and inhibited by calcium
DIETARY CONSIDERATIONS
Stable civilizations have arisen only when primitive hunting communities have
learned to cultivate cereals, such as wheat, rice maize, millets, barley, oats
and rye. In many rural areas, cereals provide more than 70% ofthe energy consumed9.
Table I shows the magnesium and calcium concentrations in these staple foods. They
contain two to eight times more magnesium than calcium, and as much as one thousand
milligrams of magnesium could be consumed if two thousand calories were obtained
from these sources. One may argue that dairy products contributed to most of the
ingested calcium This is unlikely since 50% of individuals tested so far show
allergic reactions to dairy products and lactose intolerance is
common in most ethnic groups, occurring in 70% ofBlack Americans and over 70% ofOrientals, Jews, Arabs,
Greeks, Japanese, Eskimos, Indians, Africans and Asians 23'I7'13'14,15'''24'18'8'19
'30'31
TABLE I
MAGNESIUM AND CALCIUM CONCENTRATIONS
IN SOME CEREALS
Cereal Magnesium(mg/100 Cal) Calcium(mg/100 Cal J Magnesium/Calcium Ratio
Millet 50 6.2 8.2
Maize 42 6.0 7.0
Wheat 34 no 3.1
Rye 34 11.5 3.0
Brown Rice 23 9.0 2.8
Barley II 4.6 2.3
Oai 38 18.0 2,1
Considering that 99% ofthe total body calcium is located in the bones, it is not
surprising that academic proponents ofhigh calcium intake have used as an argument
the possible role of calcium deficiency in osteoporosis 1''4'29. There is no evidence,
however, to support this view. Osteoporosis is not more common in those parts
of Asia and Africa where diets are relatively low in calcium (300-500 mg/day) than
in Europe and North America where consumption of dairy products contributes to
more thanlOOO mg of calcium/day When patients with severe osteoporosis were given
massive doses of calcium they went into positive calcium balance, but radiographic
studies revealed no changes in the osteoporotic process Where did that calcium
go? Obviously into the soft tissues where it does not belong.
Calcium balance studies have indicated that man can adapt to relatively low calcium
intake by increasing calcium absorption and decreasing urinary excretion10.
There is not such a mechanism for magnesium26. The adaptation to low calcium
intake is most likely via synthesis of 1, 25 (OH)2 D3 by the kidney. It was previously
discussed that high intramitochondrial concentrations of phosphate and calcium in the kidney
suppress the formation of 1, 25 (OH)2 D3 20'22. Therefore, mechanisms that increase
intracellular and intramitochondrial calcium would prevent adaptation to low
calcium intake. Failure ofthe calcium-pump at the cell membrane and increased uptake of
calcium by mitochondria are two such mechanisms which are both magnesium-
dependent as previously discussed. Since a low phosphate diet increases
fonnation of 1, 25 (OH)2 D3 20 and a high magnesium diet would keep calcium out
of the mitochondria, it seems therefore that one approach to improving the adaptation
to low calcium intake is to ingest a diet low in phosphate and high in magnesium Such
an approach to the management of osteoporosis would seem more
appropriate than the ingestion of massive doses of calcium. The latter approach blocks magnesium
absorption and creates a magnesium deficiency, conducive to a failure of the
calcium- pump and intracellular accumulation of calcium in soft tissues that eventually
leads to irreversible cell damage. Also, magnesium deficiency results in elevated PTH
which prevents the utilization of the absorbed calcium for bone formation and favors
soft tissue calcification.
Recent studies suggest that calcium requirements are increased by acid-ash, high-
protein and high sulfur diet21. In order to increase the efficiency of the adaptation
mechanism to low calcium intake, every attempt should be made to ingest foods
containing a magnesium/calcium ratio oftwo or more, with neutral or alkaline
ash, not excessive in phosphate, sulfur, proteins, refined sugar, fats and other
substances that drain the body ofboth calcium and magnesium Magnesium deficiency causes a
reduced intestinal absorption of calcium and decreased serum ionized calcium.
Magnesium has a calcium-sparing effect and decreases the
need for calcium.
Since magnesium suppresses PTH and increases CT, adequate magnesium intake
would improve the phosphorous balance from a low phosphate diet by increasing
phosphate absorption via the 1, 25 (OH)2 D3mechanisms and by preventing the PTH
induced phosphaturia. Furthermore, a high magnesium intake would enhance
calcium absorption by the 1, 25 (OH)2 D3mechanisms, increase serum ionized calcium,
promote deposition of calcium in the bone matrix where it belongs and minimize
cellular uptake and mitochondrial accumulation of calcium. )
With such an approach there would be no need for pharmaceutical companies to
develop new and improved calcium blockers in the management of cardiovascular
diseases, since magnesium works naturally to produce the same end result.
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