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Calcium supplements – an overview

Christel Hanson, BPharm, BScHons, MSc(Med) Pharmacy
Correspondence to: HansonC@tut.ac.za
Keywords: calcium, calcium carbonate, calcium citrate, absorption, supplement

Abstract
Calcium is an essential nutrient required for numerous biological functions. Considering the important role that calcium plays in bone health, it is necessary to
take special care to reach the daily recommended calcium intake. This overview describes the factors that can influence calcium absorption, the methodologies
used to evaluate calcium absorption, bioavailability, pharmacokinetics and pharmacodynamics, different calcium salts as well as the best approach to optimise
the intake of calcium.

© Medpharm S Afr Pharm J 2016;83(7):22-28

Introduction up of calcium and phosphorus [Ca10(PO4)6(OH)2] which provide

The need for adequate calcium intake has been the focus of
numerous studies. Calcium is an essential nutrient needed for
biological functions such as muscular contractions, miosis, blood
coagulation, nervous or synaptic impulse transmission, intracellular
signalling, hormone and enzyme secretions, though less than 1%
of total body calcium is needed to support these critical metabolic
functions. The remaining 99% is essential for structural support
of the skeleton.1 The human body cannot produce calcium and
therefore it has to be absorbed from food. Most individuals can
easily receive at least half their calcium requirement per day through
their diet.2 Many studies have demonstrated that calcium intake
prevents diseases such as osteoporosis.3 Calcium supplementation
is indicated for patients who are unable to obtain enough calcium
on a daily basis through their diet. The scope of this article is not to
discuss all the benefits of calcium, but to provide the pharmacist
with a better understanding of the absorption of the different
calcium supplements available, and how to assist their patients in
obtaining the optimal calcium required. It is often a daunting task
for patients to understand their daily requirements and how to
achieve the goals set for them. This is further complicated by the
availability of multiple supplements, each with different dosing
regimens, compounds, and the lack of product standardisation.
The physiological function of calcium in the
human body
Calcium accounts for one to two per cent of adult human body
weight and is one of the major mineral components of the skeletal
system. Calcium is present in the skeletal system in the form of
hydroxyapatite, which is an inorganic crystalline structure made
rigidity.4 Calcium is also essential for nerve conductivity, muscle
contraction, hormone and enzyme secretion and blood clotting.
Metabolism of calcium
Absorption, bioavailability and excretion of dietary
calcium
Calcium requirement is dependent on the state of calcium
metabolism, which is regulated by three main mechanisms:
intestinal absorption, renal absorption and bone turnover. These
in turn are regulated by a set of interacting hormones, including
parathyroid hormone (PTH), 1,25-dihydroxyvitamin D [1,25 (OH)2D],
ionised calcium itself, and their corresponding receptors in the gut,
kidney and bone.5 Control is mediated through the calciotropic
hormones: parathyroid hormone (PTH), calcitriol and calcitonin.4
Parathyroid hormone secreted by the parathyroid gland and
calcitonin secreted by the thyroid gland maintain calcium levels at
a range of 8.5–10.5 mg/dL. The PTH affects renal function to retain
more calcium. The kidneys filter as much as 10,000 mg of calcium
daily, with ~ 98% being reabsorbed. Serum calcium is very tightly
regulated and does not fluctuate with changes in dietary intakes.4
Calcium is absorbed by the gastrointestinal tract through active
transport, which occurs predominantly in the duodenum and
the proximal jejunum. In the distal jejunum and the ileum
calcium is absorbed via passive diffusion. The active compound is
saturable, stimulated by 1.25(OH)D3 (calcitriol) and influences the
active transport, increasing the permeability of the membrane,
regulating the calcium migration through the intestinal cells,
increasing the levels of caldindin (calcium transporting protein-
CaBP).6 Caldindin transfers the calcium ion directly into the

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epithelial cell. Calcitriol is a cholesterol derivative. Under the
influence of PTH, the kidneys convert cholecalciferol into the
active hormone, 1.25 dihydrocholecalciferol, which acts on the
epithelial cells lining the small intestine, to increase the rate of
absorption of calcium. At low intakes, calcium is mainly absorbed
by active transport, but as intakes increase, this mechanism
becomes saturated and additional calcium is absorbed by carrier-
mediated (non-saturable) diffusion. The net result is an increase in
the absolute amount of absorbed calcium with increasing intakes,
but a decrease in fractional absorption. Fractional absorption
of calcium from foods and supplements is inversely related to
the amount of calcium consumed over a range of 150–500 mg
calcium. Calcium uptake, through active transport, is controlled
by the circulating concentration of ionised calcium in the blood.
Should this fall below 1.1 mmol/L, the amount of calcium
absorbed is increased; conversely, should concentrations rise
above 1.3 mmol/L, absorption is reduced.4 Low levels of PTH in
the blood inhibit calcium absorption from the gut.
Vitamin D is essential for the absorption of calcium in the intestines.
Calcitriol, the active form of vitamin D, increases the absorption of
calcium. The PTH stimulates calcitriol synthesis from cholesterol.
Vitamin D3 (cholecalciferol) is produced from sun exposure
while vitamin D2 (ergocalciferol) is acquired by food intake.6 The
absorbed vitamin D reaches the lymphatic system through the
cholymicrons entering the bloodstream and is transported to the
liver, bonded to the vitamin D transporter protein (DBP). In the
liver it is hydroxylated to 25-hydroxyvitamin D [25(OH)D] where it
is stored. Once the calcium concentration falls, 25(OH)D bonds to
the DBP, is transported to the kidneys and released in the tubular
renal cell and again hydroxylated, forming 1.25- dihydroxyvitamin
D [1.25(OH)2D], the biological active form. Vitamin D is stored
in the liver and becomes available through hydroxylation in the
renal tubules to its active form 1,25(OH)2D3.⁷
Factors that influence calcium absorption, bioavailability
and excretion of calcium
Amount consumed: The efficiency of absorption increases as
calcium intake decreases.1 As calcium intake increases (> 500 mg/
day), passive diffusion presents a greater absorption of calcium.⁶
Age and life stage: Calcium absorption is as high as 60% in infants
and young children. Growth hormone (GH) can promote calcium
absorption indirectly activating the renal 1α hydroxylase and
elevating the serum concentration of 1,25 (OH)2D3.⁶ Absorption
decreases to 15–20% in adulthood, increases in pregnancy and
continues to decrease in women and men older than 50 years.1
Pregnancy and lactation: Fractional calcium absorption is
increased from 20–30% and up to 60% during the last trimester.
This increase is associated with an increased plasma concentration
of calcitriol, suggesting vitamin D plays a role. In addition, the
hormones oestrogen, lactogen and prolactin may stimulate
increased active calcium absorption. Increased bone mineral
resorption from the mother’s skeleton liberates calcium, making
it available for the foetus. During lactation, approximately
S Afr Pharm J 23
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250 mg of calcium is secreted in breast milk. Maternal urinary
calcium excretion is reduced and bone resorption increased.
Following the resumption of menstruation, calcium absorption
increases, due to increased oestrogen concentration, stimulating
calcitriol production, and bone mineral density begins to increase.4
Postmenopausal women: Decreased oestrogen production
increases bone resorption and decreases calcium absorption,
resulting in bone loss. A decrease in oestrogen levels is associated
with decreased calcitriol production and thus reduced calcium
absorption. Annual decreases in bone mass of 3–5% per year
frequently occur in the first years of osteoporosis.1
Vitamin D intake: Calcium absorption is dependent on an
adequate level of the active form of Vitamin D, calcitriol.1 The
inactive form of vitamin D3 (colecalciferol) is produced through
cutaneous synthesis and solar exposition is responsible for 80–90%
of the stocks of vitamin D. Vitamin D2 (ergocolecalciferol) is the
dietary form of the vitamin, which is found in egg yolk, cheese
and beef liver.6 Persons who are not exposed to sunlight should
use Vitamin D supplements. Pharmacological dosing of vitamin D
supplementation, 25-hydroxyvitamin D3, should be done under
medical supervision.4
Vitamin K2: Vitamin K2 (menaquinone) facilitates the action of
osteoblasts in the ossification of new skeletal material. Osteoblasts
produce the protein osteoblastin, which binds calcium to the bone
matrix. Vitamin K2 activates osteocalcin. Studies have shown levels
of vitamin K2 were low in patients with osteoporotic fractures. In
nature vitamin K2 is synthesised by bacteria and small amounts are
available from fermented foods, milk products, especially cheese,
and meat. Changes in diets and food-processing techniques have
reduced the levels of vitamin K2 ingested in food. The daily value
(DV) recommended supplementation of vitamin K2 is 180 mcg per
day for adult males and 90 mcg for adult females.8,9,10
Other components of food: Phytic acid and oxalic acid, found
naturally in green vegetables (e.g. cabbage, spinach, broccoli and
beans), bind to calcium, forming insoluble complexes, and inhibit
calcium absorption. Wheat products (except wheat bran) do not
appear to inhibit calcium absorption.1 Dietary milk proteins and
lactose increase calcium solubility and the osmolarity of calcium
in the ileum, stimulating passive diffusion.6
Bioactive compounds: Bioactive compounds such as indigestible
oligosaccharides (inulin, fructans) are resistant to hydrolysis of
food enzymes. Once they are not hydrolysed and absorbed in
the stomach and small intestines, these compounds undergo
partial or total fermentation when entering into the large
intestine. Fermentation leads to the production of short chain
fatty acids, which results in the acidification of the intestines and
consequently stimulation of calcium absorption.6
Sodium intake: High sodium intake increases urinary calcium
excretion. An increase of 100 mmol (2 300 mg) of sodium in the
diet (equivalent to 5.75 g table salt) leads to a 1 mmol (40 mg)
increase in calcium excretion in the urine.4
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Protein intake: High protein intake was previously thought
to increase calcium excretion and was therefore thought to
negatively affect calcium status. However, more recent research
suggests that high protein intake also increases intestinal calcium
absorption. Diets low in protein may increase concentrations of
PTH and calcitriol in the short term, and may be detrimental to
skeletal health in the long term.11
Caffeine intake: The effect of caffeine in tea and coffee can
affect calcium excretion moderately. One cup of regular brewed
coffee causes loss of 2–3 mg of calcium. Massey (2005) found that
moderate caffeine consumption of one cup of coffee and two cups
of tea per day, has no harmful effect on bone status in individuals
who ingest the recommended daily allowance of calcium.12
Alcohol intake: Alcohol can reduce the absorption of calcium.
Alcohol also inhibits liver enzymes converting vitamin D to its active
form. Cortisol levels increase with excessive alcohol consumption
resulting in less osteoblast activity and increased osteoclast
activity in the bone, resulting in bone resorption. Chronic alcohol
consumption increases PTH which leaches calcium from bone.
In men, testosterone levels decrease resulting in an increase in
osteoclast activity and bone resorption. A detrimental effect of
alcohol consumption on bone may occur only when in excess
of three glasses of wine per day is consumed. Alcoholics have a
2.8-fold increased risk for bone fractures and a 23% prevalence of
osteoporosis.13
Disease conditions: Disorders that influence calcium absorption
include hyperparathyroidism, diseases of the kidney, achlorhydria
and liver cirrhosis.13
Recommended intakes
Dietary Reference Intake (DRI) is the general term for the set of
reference values used for planning and assessing the nutrient
intakes of healthy people. These values vary by age and gender.
Recommended Dietary Allowances (RDA) represent the average
daily level of intake sufficient to meet the nutrient requirements
of nearly all (97–98%) healthy individuals. Table I lists the RDA for
calcium as published by The National Osteoporosis Foundation of
South Africa (NOFSA).2
Table I: Recommended Daily Allowance of calcium (National Osteoporosis
Foundation of South Africa)
Age group Elemental calcium per day (mg)
Infants 1000
Children and adolescents 1500
Young adults 1000
Pregnant and lactating females 1500
Post-menopausal women
• On hormone replacement therapy 1000
• No hormonal replacement therapy 1500
Vitamin D
Recommended RDAs for vitamin D are as follows: men and
women aged 19 to 70 years, 600 international units (IU); and men
S Afr Pharm J
and women older than 70 years, 800 IU. For maximal benefit to
bone, cognition, and neuromuscular health, 25(OH)D levels in the
blood should be at least 30 ng/mL (75 nmol/L). When 25(OH)D
levels are below 20 ng/mL, the patient has vitamin D insufficiency,
and when they are below 20 ng/mL (50 nmol/L), the patient has
vitamin D deficiency.14
Calcium supplements (combinations, salts and
absorption)
Although obtaining calcium from dietary sources is preferable,
calcium supplementation may be warranted in some patients,
such as older adults with osteoporosis. Calcium supplements
are derivatives of natural products, such as oyster shell or bone.
Several different calcium compounds are used in supplements,
including calcium carbonate, calcium gluconate, calcium
phosphate and calcium citrate. Calcium carbonate is the most
common supplement but is less soluble in water. Calcium citrate
has an acidic base. This acidity requires less production of natural
stomach acids, allowing this type of calcium to be better absorbed
than the carbonate form. It does, however, have less elemental
calcium concentration (20%) and low bioavailability.15
These compounds contain different amounts of elemental
calcium. Table II indicates the elemental calcium in the different
calcium compounds in calcium supplements available in South
Africa.2
If 500 mg elemental calcium is required, 1 250 mg of calcium
carbonate should be administered (40% of 1 250 = 500), 2 000 mg of
calcium citrate compound will provide 500 mg elemental calcium
(24% of 2 000 = 500) etc.2
Calcium supplements are best absorbed when taken several
times per day in amounts of 500 mg or less. Initiating calcium
supplementation, the dose should be gradually increased, starting
with 500 mg per day for the first week and increased slowly.
Calcium carbonate is the most concentrated form of calcium,
allowing for smaller quantities to be used.2 Calcium citrate is
better absorbed than calcium carbonate, but is more expensive
and more of the supplement needs to be taken because the
elemental calcium content is half that of calcium carbonate.
Calcium is best absorbed in an acidic environment, thus should
be taken with food. Food stimulates secretion of gastric acid and
slow gastric emptying allowing better dispersion, dissolution and
absorption of less soluble preparations. A light meal increases the
absorption of calcium carbonate with 20–25%. Calcium carbonate
and calcium citrate present a similar absorption when taken with
food.6 Most branded products are absorbed easily in the body.2
Intestinal absorption of calcium does not necessarily reflect
bioavailability of calcium.6
Calcium carbonate is a relatively insoluble salt, while calcium
citrate is more soluble. As mentioned earlier, food stimulates
gastric secretion, increasing the solubility of calcium carbonate
salts. Calcium citrate’s solubility is independent of the secretion
of gastric acid.6 An easy way to test a product for solubility is to
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Table II: Elemental calcium salts and vitamin D concentration in calcium products
Calcium salt % Elemental Available product in South Africa Elemental calcium Vitamin D
calcium per dosage form
Calcium carbonate 40 Calcium (Revite) 875 100
Caltrate 600+D (Pfizer) 600 400
Sandoz Calcium Optimum+® (Sandoz) 600 400
Osteochoice® (Sanofi) 600 400
B-Cal-DM (iNOVA) 500 400
B-Cal-Ultra (Georen) 500 400
Calsuba® powder (GSK) 500 200
Emvit® Cal-D3 500 200
Menacal 7 (Ascendis Health) 500 400
Chewable calcium wafer (Solgar) 500 -
Vital calcium (Vital) 400 1.25
Caltrate D (Pfizer) 300 100
Calcium phosphate 30-40 Osteoscript® (Calcium-s-amino ethanol phosphate calcium 200 50
biglycinate) (Medford®)
Calcium citrate 24 Chelated calcium® (calcium glycinate amino acid chelated, calcium 1000 -
carbonate) (Solgar)
Calcium citrate (GNC) 1000 -
Calcium citrate malate 24 Advanced calcium complex® 1000 1000
(Calcium as dicalcium malate, citrate glycinate aminoacid chelate)
(Solgar)

add the calcium product to some vinegar. If it has not dissolved
after 30 minutes, it will probably not dissolve in the stomach.2
Methods to test the bioavailability of nutrient balance include
balance serum concentrations, urinary excretion, serum (or
body) tracer concentrations, biomarkers, and in vitro testing
(dissolution and disintegration). Hanzlik (2005) compared the
oral bioavailability of calcium formate, calcium carbonate and
calcium citrate using the calcium blood serum and serum intact
parathyroid hormone (iPTH) methods, with immunoradiometric
assay, to test bioavailability.16 Changes in serum calcium are
often mirrored by opposite but amplified changes in serum iPTH
concentration. These changes are a pharmacodynamic indicator
or biomarker of changes in serum calcium. For example, a 5%
increase in serum calcium can elicit a 40% to 50% decrease in
serum iPTH. In this study, serum calcium carbonate concentration
increased with 4% and a fall in serum iPTH of 20–40%. Calcium
citrate showed a modest change in serum calcium of 9%, while
calcium formate had a 15% increase in serum calcium and 70%
decrease in iPTH. In a randomised trial by Kressel et al, different
organic calcium salts, calcium lactate malate and calcium
lactate citrate, had almost the same bioavailability as calcium
carbonate and calcium gluconate.17 The total serum calcium as
calcium lactate citrate 7.6%, calcium lactate malate7.4%, calcium
carbonate 5.5% and calcium gluconate 5.8%, two hours after
ingestion. Intact parathyroid hormone concentration showed
the expected depression for the calcium salts. In a similar study,
Heller et al reported calcium citrate to be more bioavailable than
calcium carbonate, when given with a meal.18
More important than the solubility, absorption and bioavailability
of calcium salts is the quality of the supplements’ formulation. Badly
formulated pharmaceutical compounds do not disintegrate when
in contact with gastric secretions, diminishing their absorption.6
Analysis done by an independent laboratory, Labdoor laboratories
(USA), on 30 calcium supplements available in the USA, found
that the average product nearly matched its label for calcium,
exceeding its claims by 3.8%. All 30 products contained no traces
of heavy metal while the nutritional value scored an average of
9.6 out of 10. The projected efficacy tested indicated the average
product contained 701.0 mg of calcium and 820.8 IU of vitamin
D3 per serving. Products were scored and ranked. Of the products
available in South Africa, the scores were as follows (ranking
in brackets and scores A–-F): Solgar® calcium magnesium with
Vitamin D3 (2nd; A); GNC® calcium citrate (4th; A-); Caltrate® calcium
and vitamin D3 (29th; C-).19
Dosage forms and combination products
Oral calcium supplements are available in different delivery
vehicles: chewable tablets, powder base, water dispersible
and conventional tablets. In a 2013 study, patients preferred
conventional tablets to chewable tablets and liked powder-based
calcium supplements the least.21 Many supplements contain
combinations of vitamin D, vitamin K2, zinc, magnesium and boron.
These supplements are formulated to contain the recommended
RDA per tablet, with a dosing interval of two to three times per
day. Refer to Table II for calcium and vitamin D content of some of
the calcium supplements available in South Africa.

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Table III. A comparison between the different calcium salts

Calcium salt Absorption and bioavailability
Calcium carbonate • Alkaline-based compound found in nature in shells, rocks, limestone
• Highest concentration of elemental calcium (35–40%)
• Bioavailability in humans 15–40%20
• Needs stomach acid to be absorbed, to be taken with food
Calcium citrate • Acidic base
• Less elemental calcium than calcium carbonate (20%)
• Better absorbed than calcium carbonate (22–27%)
• Bioavailability (21%)6
• Requires less stomach acid to be absorbed. Can be taken any time of day
• Suitable for aging patients with impaired gastric function, inflammatory bowel disease or achlorhydria
• Preferable for patients using acid blockers (PPI)
Calcium citrate malate • Formed from calcium salt of citric acid and malic acid
• Contains 26% elemental calcium
• Bioavailability 42%
• Absorption rate of 36–37%, due to its water-solubility and method of dissolution
• Can be taken with or without food
• Suitable for aging patients with impaired gastric function, inflammatory bowel disease or achlorhydria
• Preferable for patients using acid blockers (PPI)
• Vegetarian calcium source
Calcium lactate • Present in foods such as aged cheese and baking powder
• Low amount of elemental calcium (9–13%). Bioavailability is acceptable
• Can be absorbed at various pH’s in body20
Calcium gluconate • Low amounts of elemental calcium (9–13%)20
Calcium phosphate • Absorption level similar to calcium carbonate
• Elemental calcium of 31–38%20
• Bioavailability of 38% (tricalcium phosphate)6

Adverse effects
Adverse effects occur most frequently with calcium carbonate.
The most common adverse effects of calcium supplementation
are constipation, bloating and excessive gas. Excessive gas
and bloating are due to the chemical reaction between
calcium carbonate and the hydrochloric acid in the stomach.
CaCO3(s) + 2 HCl(aq) = H2O(l) + CO2(g) + CaCl2(aq).22
Calcium and medication interaction
Calcium supplements have the potential to interact with several
prescription drugs and over-the-counter medications.
Decrease in calcium absorption
• Iron supplementation: An insoluble calcium-iron complex is
formed when taken together orally. They should be taken two
hours apart.23
• Tetracycline and fluoroquinolones: They form an insoluble
complex with calcium which is not absorbed. They should be
taken two hours apart.23
• Bisphosphonate: The calcium supplement should not be
taken in the morning as it will interfere with absorption of
bisphosphonates. The calcium supplement should be taken at
noon and night.2
function. They increase renal calcium excretion and decrease
gastrointestinal calcium absorption, resulting in reduced serum
calcium. Reduced serum calcium causes increased secretion of
PTH, and glucocorticoids increase PTH sensitivity. PTH action
in turn stimulates osteoclast activity.24 Glucocorticoids also
decrease intestinal calcium absorption, in part by opposing the
action of vitamin D, and by decreasing the expression of calcium
channels in the duodenum. In addition, glucocorticoids increase
renal calcium excretion by decreasing calcium reabsorption.25
• Thiazide diuretics: This can interact with calcium carbonate and
vitamin D-supplements, increasing the risk of hypercalcaemia
and hypercalcuria.1
• Aluminium and magnesium-containing antacids: Urinary
calcium excretion is increased.2
• Proton pump inhibitors: Inhibition of the proton pump reduces
the fraction of calcium absorbed from calcium carbonate
in postmenopausal women. Long-term treatment with PPI,
especially at high doses, is associated with increased risk of hip
fractures.7
Increase in calcium absorption
Magnesium: Low magnesium levels stimulate calcium excretion
in the urine. Supplementation with magnesium should only be
undertaken when blood results confirm hypomagnesium.23

• Glucocorticosteroids: Glucocorticoids reduce bone remodelling Vitamin D3: The RDA for Vitamin D is 800 UI per day in persons
by directly modulating osteoclast, osteoblast, and osteocyte younger than 70 years and 1 200 IU in persons older than

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70 years. Persons who are not exposed to sunlight should use
Vitamin D supplements. Pharmacological doses of vitamin D
supplementation, 25-hydroxyvitamin D3, should be done under
medical supervision.2
Calcium affecting drug serum levels
Digoxin serum levels may decrease when calcium is used together
with digoxin.23
Fluoroquinolones, levothyroxine, tetracycline, phenytoin: These
drugs decrease the absorption of calcium supplements and
dosing should be spread two hours apart.25
Iron supplements: Calcium salts chelate the iron in supplements
and prevent the absorption of iron.23
Calcium supplementation risk/benefit ratio
Cardiovascular disease: Meta-analysis of randomised controlled
trials by Bolland et al, first published in 2008, raised the risk of
possible increase in risk of adverse cardiovascular events in women
and men associated with the use of calcium or calcium plus vitamin
D supplements.25 Similar results in some aspects were reported by Li
et al.23 These published articles were reviewed by Heaney et al, after
a number of issues were raised, such as inadequate compliance
with intervention and use of nontribal calcium supplements.3
They concluded that “the authors do not believe that the evidence
presented to date (2012) regarding the hypothesised relationship
between calcium supplement use and increased cardiovascular
disease risk is sufficient to warrant change in the Institute of
Medicine recommendations, which advocate use of (calcium)
supplements to promote optimal bone health in individuals who
do not obtain recommended intakes of calcium through dietary
sources”.3 Adverse effects of calcium supplementation on the
cardiovascular system could be mediated through hypercalcaemia.
These adverse effects occur when excessively high calcium intakes
(more than 1 400 mg/day) override normal homeostatic control of
serum calcium levels. Hypercalcaemia has been associated with an
increased risk of death from cardiovascular disease and ischaemic
heart disease, but not from stroke.26 Concern has recently arisen
about the potential adverse effects of excessive calcium intake,
i.e. calcium loading from supplements, on arterial calcification
and risks of cardiovascular diseases (CVD) in older adults. Healthy
kidneys have limited capability of eliminating excessive calcium
in the diet; the likelihood of soft-tissue calcification may increase
in older adults who take calcium supplements, particularly in
those with age or disease-related reduction in renal function.
Current studies are inconclusive on the increased risk of vascular
calcification, and further studies are needed.27
Reid et al noted a 7% increase in HDL cholesterol and a 16% increase
in HDL to LDL cholesterol ratio following consumption of 1 000
mg calcium per day over a period of a year in postmenopausal
women. This may be associated with a 20–30% reduction in
cardiovascular events.28
Gastritis: Calcium carbonate may cause gastritis if taken between
meals as this can stimulate rebound acid production in the
stomach.2
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Kidney stones: No scientific evidence exists that calcium causes
kidney stones. In hypercalcuria, it is advised to limit calcium
intake to 1 000 mg per day. In normal urinary calcium levels in
the presence of kidney stones, it is not necessary to limit calcium
intake, but vitamin D supplementation should be used with
caution.2
Post menopause: The Women’s Health Initiative (WHI) found a
relative risk reduction of 29% in hip fractures in those women on
treatment of 1 000 mg calcium carbonate and 400 UI of vitamin D.⁷
Cancer: Evidence from prospective cohort trials support the
protective effect of calcium against colorectal cancer. A high
calcium intake (> 1 000 mg/day) may reduce the risk of colorectal
cancer between 15–40%.⁴ Any calcium that is not absorbed and
passes into the colon is capable of forming insoluble calcium
“soaps” with phosphate, free fatty acids and free bile acids, thus
reducing the concentrations and toxicity of free fatty acids and
free bile acids.⁴ Case-control studies suggest inverse association
between calcium consumption and the risk of breast cancer.
Women who consume more total calcium (from diet and
supplements) are, on average, 20% less likely to develop breast
cancer than women who consume less.⁴
Weight management: Evidence for a possible anti-obesity effect
of calcium comes from a small number of studies conducted in
overweight adults. A higher intake of calcium was associated with
a greater reduction of body fat (4.4%) compared to the control
group and a significant reduction in waist circumference was
observed.29 Further research is required in this area to determine
whether or not calcium plays a role in weight management. It is
too early to promote weight-loss benefits of additional calcium
supplements.4
Pre-eclampsia: Calcium supplements during pregnancy may
reduce the risk of pre-eclampsia, but the benefits may apply
only to patients with inadequate calcium intakes. The American
College of Obstetrics and Gynecology recommends 1 500–2 000
mg calcium supplement, to reduce the severity of pre-eclampsia
in pregnant women who have dietary calcium intakes of less than
600 mg per day.1
Conclusion
Although obtaining calcium from dietary sources is preferable,
calcium supplementation may be warranted in some patients,
such as older adults with osteoporosis. From the numerous
studies published it is clear that the absorption of calcium
carbonate is high, if taken with meals. Calcium citrate has a higher
absorption than calcium carbonate, though it is a more expensive
product. The difference in the absorption and bioavailability
of the different calcium salts is very little. Serum levels of
vitamin D, disease conditions and medication have a bigger
influence on the absorption of calcium than the type of calcium
salt. The “best” calcium supplement is the one that meets
an individual’s needs based on lifestyle, disease conditions,
medication, tolerance, convenience, cost and availability.
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calcium citrate, and calcium carbonate. The American Society for Pharmacology and Ex-
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