192 Introduction to Human Nutrition
concentration to normal (Figure 9.2). At the kidney,
PTH promotes the reabsorption of calcium in the
distal tubule. PTH affects the intestine indirectly by
stimulating the production of 1,25(OH) 2 D 3 (in the
kidney), which, in turn, leads to increased calcium
absorption. PTH also induces bone resorption (by
signaling osteoclasts), thereby releasing calcium into
blood. Owing to the action of PTH and 1,25(OH) 2 D 3
on the target tissues, plasma calcium concentrations
are restored within minutes to hours.
If, however, there is a continual inadequate intake
or poor intestinal absorption of calcium (e.g., because
of vitamin D defi ciency), circulating calcium concen-
tration is maintained largely at the expense of skeletal
mass, that is, from an increased rate of bone resorp-
tion. This PTH-mediated increase in bone resorp-
tion is one of several important causes of reduced
bone mass and osteoporosis. The cumulative effect of
calcium depletion (by whatever mechanism) on the
skeleton over many years contributes to the increas-
ing frequency of osteoporotic fractures with age.
Prolonged inadequate calcium intake in younger
people reduces the rate of accretion of the skeleton
and may prevent the attainment of the genetically
determined maximal PBM. This may increase the risk
of osteoporosis as the PBM in adulthood is predictive
of bone mass in later life. Chronic inadequate intake
or poor intestinal absorption of calcium may also play
some role in the etiologies of hypertension, including
pre-eclampsia and colon cancer. Calcium intake may
also play a role in body weight regulation; however,
this requires further investigation.
Toxicity
The available data on the adverse effects of high
calcium intakes in humans are primarily from the
intake of calcium from nutrient supplements. The
three most widely studied and biologically important
are:
● kidney stone formation (nephrolithiasis);
● the syndrome of hypercalcemia and renal insuffi -
ciency, with or without alkalosis (referred to his-
torically as milk alkali syndrome associated with
peptic ulcer treatments);
● the effect on absorption of other essential minerals,
e.g., iron, zinc, magnesium and phosphorus.
Based largely on the data concerning the association
of high calcium intakes with hypercalcemia and renal
insuffi ciency in adults, the US Food and Nutrition
Board established a tolerable upper intake level (UL)
of calcium of 2500 mg/day for children, adolescents,
and adults, as well as pregnant and lactating women.Genetic diseases
Two rare inborn errors of vitamin D metabolism,
vitamin D-dependent rickets types I and II, have an
associated hypocalcemia that can impair the bone
calcifi cation process. Type I vitamin D-dependent
rickets appears to be caused by mutations in the
enzyme 25(OH)D 3 -1-α-hydroxylase [responsible
for the synthesis of 1,25(OH) 2 D 3 from 25(OH)D 3 ],
leading to defective activity of this enzyme, whereas
type II vitamin D-dependent rickets, which is associ-
ated with normal or elevated levels of 1,25(OH) 2 D 3 ,
is thought to result from target tissue resistance to the
action of 1,25(OH) 2 D 3. This resistance arises owing
to changes in the vitamin D receptor molecule. Daily
vitamin D 3 administration seems to be an effective
therapy for both disorders.
A hypercalcemia has been noted in familial benign
hypercalcemia (types I and III). Type I familial benign
hypercalcemia, a renal tubular defect in calcium
reabsorption, is caused by a mutation in the gene
encoding the calcium-sensing receptor. Type III
familial benign hypercalcemia represents a distinct
genetic entity. However, the gene(s) responsible for
this type of hypocalciuric hypercalcemia is still being
mapped.Assessing status
There is, as yet, no biochemical indicator that refl ects
calcium nutritional status. Blood calcium concentra-
tion, for example, is not a good indicator because it
is tightly regulated. There are, however, some poten-
tial indicators of nutritional calcium adequacy, which
are related to content or metabolism of the skeletal
calcium reserve. Measures of bone mass may be used
as indicators of body calcium status. These include
bone mineral content (BMC, which is the amount of
mineral at a particular skeletal site such as the femoral
neck, lumbar spine, or total body) and bone mineral
density (BMD, which is BMC divided by the area of
the scanned region). Besides their relationship to
bone mass and strength, BMD and BMC are strong
predictors of fracture risk and are thus functional
indicators of calcium status. The US Food and
Nutrition Board used data relating dietary calcium