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Calcium and Calcium Salts

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100 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017

DRUG CORNER

Calcium and Calcium Salts

Abhijit Trailokya1, Ambrish Srivastava2, Milind Bhole3, Nitin Zalte3

and cheese) and amongst the plant

Abstract foods are green leafy vegetables
Calcium is the most abundant mineral in the body. Bones and teeth like amaranth, fenugreek leaves
and broccoli. Cereals like Ragi,
contain approx. 99% of calcium. Calcium exists in both plant and animal
nuts and seeds like almonds,
foods. The best source of calcium is milk. Indian Council of Medical
pistachios and sesame seeds, fishes
Research (ICMR) recommends 600-800 mg/day of calcium which increases
like salmon, sardines etc. are good
to 1200 mg/day in pregnant and lactating mothers. Inadequate calcium
sources of calcium.
intake for longer duration is responsible for osteopenia and osteoporosis.
Prevention and treatment of osteoporosis is frequently done with The best source of calcium is
milk. For Infants mother’s milk is
calcium supplementation. Calcium deficiency can be treated with various
excellent score of calcium. The milk
calcium preparations, organic salts like tricalcium citrate, calcium lactate,
of cows, buffaloes and goats is rich
calcium lactate gluconate, calcium gluconate and inorganic salts like
in calcium. The calcium in milk
calcium chloride, calcium carbonate and calcium phosphate. Appropriate
is accompanied by a favourable
calcium salt selection depends on calcium content, solubility, taste
proportion of phosphorus, hence,
and bioavailability as well as cost of available preparations. The most it is very well utilised in the body.
commonly available salt forms are calcium carbonate and calcium citrate.
Milk products such as curd,
Calcium Carbonate provides with 40% elemental calcium, better absorbed
paneer, mava, are decent sources
and well tolerated especially when taken with a meal. It is the most
of calcium. The millet ragi and
commonly used and least expensive calcium salt as cost is a consideration
seasame seeds (til) have a high
for many patients. Calcium Citrate provides 21% of elemental calcium and
concentration of calcium. Green
better absorbed than calcium carbonate in patients with higher gastric leafy vegetables are a good source
pH. Calcium lactate and calcium gluconate do not contain adequate of calcium, though only a part of
amount of calcium hence not a choice for practical use. Data available the calcium from these is available
on hydroxyapatite as a calcium source is limited. Calcium supplements to the body (Tables 1 and 2).
are also derived from natural sources such as coral, dolomite and oyster
F r e s h a s we l l a s d r i e d f i s h ,
shell. Calcium from a coral has not been proven to be better than other
especially small fresh fish, if the
calcium sources. Coral calcium products and Dolomite supplements bones are also eaten, provide
may also contain unsafe amounts of lead along with other heavy metals. substantial quantities of calcium
In clinical practice, to obtain optimal clinical outcomes, the dose of in the diet. Besides these, some
elemental calcium should not exceed 500 mg at one time. An adequate spices such as cumin seeds
calcium intake through proper selection of calcium salt is one of the (jeera), coriander seeds (dhaniya),
measures to ensure a healthy skeleton. contain enough calcium to make
a contribution, if these are used
frequently in sufficient quantity,

C alcium is the most abundant

mineral in the body. Around
99% of total body calcium is stored
secretion of hormones and enzymes,
and sending messages through the
nervous system.
in the diet.

i n th e b o n e s a n d teeth, where
it is essential for growth and
maintenance. Calcium in the bones
amounts to 25 g at birth and builds
up to about 1200 g in an adult.
Around 1% is found in the blood,
muscle, and cell fluids where it
is needed for muscle contraction,
heart contraction, blood clotting,
Recommended Dietary
Calcium is present in both plant Allowances of calcium for
and animal foods. The richest source Indians2
of calcium amongst animal foods
are dairy products (milk, yoghurt Indian Council of Medical
Research (ICMR) recommends more
1
Deputy General Manager, 2VP Medical, 3Medical Advisor, Medical Department of Alkem laboratory, Mumbai,
Maharashtra
Received: 21.08.2016; Accepted: 20.09.2016
 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 101

Table 1: Bioavailability of calcium Table 2: Food sources of calcium2 Table 3: Calcium equivalents3
from selected foods1
Foods Calcium mg/ content Calcium Salt Elemental Ca
Cauliflower, watercress, ≥50% for 100 edible Salts
brussels sprouts, rutabaga, absorbed portion Calcium 1g 19.9 400 mg 9.96
kale, mustard greens, broccoli, Milk and Milk Carbonate mEq mmol
turnip greens Products Calcium 1g 10.5 211 mg 5.26
Milk, calcium-fortified soy ≈30% Buffalo’s milk, cow’s 120-210 mg Citrate mEq mmol
milk, calcium-set tofu, Absorbed milk, goat’s milk, Malate
cheese, yogurt, calcium fortified curds (cow’s) Calcium 1g 13.6 273 mg 6.80
foods and beverages Cheese, khoa, 790 -1370 mg Chloride mEq mmol
Almonds, sesame seeds, pinto ≈20% skimmed milk Calcium 1g 3.29 66 mg 1.64
beans, sweet potatoes Absorbed powder and whole Glubionate mEq mmol
Spinach, rhubarb, Swiss Chard ≤5% milk powder Calcium 1g 4.08 82 mg 2.04
Absorbed Fish Gluceptate mEq mmol
Bacha, katla, mrigal, 320-650 mg Calcium 1g 4.65 93 mg 2.32
calcium for growing children and pran and rohu Gluconate mEq mmol
adolescents. Though recommended Nuts and Oilseeds Calcium 1g 12.6 253 mg 6.30
dietary allowances for calcium Acetate mEq mmol
Coconut dry, 130-490 mg
are about 600-800 mg/day, it is almond, mustard
desirable to give higher quantities application is usually based on
seeds and sunflower
of calcium for adolescents to seeds the consideration of a number
achieve high peak bone mass. A Gingelly seeds 1450 mg of properties associated with
normal adult male and female Cumin seeds 1080 mg the respective product such as
requires 600 mg/day. Calcium RDA Green leafy solubility, calcium content, taste
increases to 1200 mg/d for pregnant vegetables a n d b i o a va i l a b i l i t y . E c o n o m i c
and lactating mothers. Amaranth, 500-800 mg considerations are additional
cauliflower greens, important factor. 6
curry leaves,
Calcium Equivalents3 knol-khol leaves Depending on the medical
Agathi 1130 mg condition, for those children and
Calcium can be calculated by the adolescents who are unable to
Colocasia leaves 1540 mg
amount of the calcium salt (mg of consume enough calcium from
Cereals and Legumes
the cation plus the anion, or mL of dietary sources, including fortified
a specified concentration) or the Ragi, bengalgram 200-340 mg
(whole), horsegram foods, calcium supplementation
amount of elemental calcium in (whole), rajmah and can be prescribed.
milligrams (mg), in milliequivalents soyabean
(mEq), or in millimoles (mmol) Calcium supplementation is
(Table 3). acidic environment, age, estrogen commonly used for the prevention
levels, and dietary fibre intake and treatment of osteoporosis.
Calcium Deficiency play a role in calcium absorption. There are several calcium salts
Calcium absorption declines and formulations available on the
Inadequate intake of dietary with age, low vitamin D levels, market worldwide. Many calcium
calcium from food and supplements hypochlorhydria, low estrogen supplement formulations contain
produce no obvious symptoms levels, and a high-fibre diet. 5 additional ingredients such as
in the short term. Circulating vitamin K and/or magnesium. 5
blood levels of calcium are tightly Supplemental Sources of The most common forms of
regulated. Over the long term, Calcium c a l c i u m a va i l a b l e a r e c a l c i u m
inadequate calcium intake causes carbonate and calcium citrate. Other
osteopenia which if untreated They are many sources of
forms of calcium include lactate,
can lead to osteoporosis. The risk calcium available for treatment of
gluconate, and hydroxyapatite.
of bone fractures also increases, calcium deficiency. Milk, minerals
Calcium supplements are available
especially in older individuals. comprised mainly of calcium
as capsules, tablets, chews,
Calcium deficiency can also phosphate; organic salts like
powders, and liquids.
cause rickets, though it is more tricalcium citrate, calcium lactate,
commonly associated with vitamin calcium lactate gluconate and When recommending calcium
D deficiency 4 calcium gluconate and inorganic supplements, the bioavailability
salts like calcium chloride, calcium of calcium, , use of H2 blockers or
Calcium absorption from gut protein-pump inhibitors, presence
depends upon number of factors. carbonate and calcium phosphate
(Table 4). 6 of achlorhydria, number of tablets
Absorption is greatest when the n e e d e d t o a c h i e ve t h e d e s i r e d
intake of calcium is low and the The selection of the appropriate
dose, size of the tablet, form of
need is high. Vitamin D levels, an calcium source for a specific
the calcium, and cost should all be
102 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017

Table 4: Oral calcium salts comparison5 absorption disorders. Calcium

Formulation % Elemental Comments citrate supplements should also
Calcium be recommended for individuals
(W/W) treated with H2 blockers or proton
Calcium Carbonate 40 Provides the highest amount of elemental calcium. pump inhibitors. Additionally,
Most widely use. busy individuals who find it
Well absorbed and well-tolerated specially when taken with difficult to supplement at meals
a meal. should use calcium citrate, which
Limited solubility and absorption in patients with high can be taken with or without food. 4
gastric pH.
Formulation of choice in patients with hyperphosphatemia
Calcium Citrate-Malate is
in chronic Renal failure due to good phosphate binding formed from the calcium salt
ability. of citric acid and malic acid.
Calcium Citrate 21 Better absorption than calcium carbonate, in patients with Calcium citrate-malate contains
Malate higher gastric pH. about 26% elemental calcium, its
Recommend for those on H2- blocker or PPI, those bioavailability is as high as 42%,
suspected with achlorhydria, inflammatory bowel disease,
or absorption disorders.
and it also has the most consistently
high bioavailability (consistently
Can be taken on empty stomach.
over 35%) across human studies. It
More doses necessary to get the equivalent elemental
calcium compared to calcium carbonate. is one of the most heavily studied
Formulation of choice in patients with achlorhydria. forms of calcium in the area of
Calcium Citrate Malate is also recognized as a calcium
bone health and considered the
source that does not increase the risk of kidney stones, and most effective vegetarian form of
in fact it protects against stone-forming potential.7 calcium. Calcium citrate-malate’s
Calcium Phosphates 31-38 Low solubility compared to calcium carbonate. bioavailability is possible due
Calcium Acetate 25 Formulation of choice in patients with hyperphosphatemia t o i t s wa t e r - s o l u b i l i t y a n d i t s
in chronic renal failure due to good phosphate binding method of dissolution. Upon being
ability.
dissolved, it releases calcium ions
Eighty percent of the elemental calcium is bound to
phosphorus in the body and excreted. and a calcium-citrate complex. The
Calcium Gluconate 9 Multiple doses need to be taken to get sufficient amount of special structure of calcium citrate-
elemental calcium. malate makes it 6 to 9 times more
More soluble than calcium citrate easily dissolved in the stomach
Calcium Lactate 13 Multiple doses need to be taken to get sufficient amount of than plain calcium citrate, with an
elemental calcium. absorption rate of 36-37% in tablets
Similar solubility as calcium gluconate and capsules, or higher if dissolved
in orange juice. Calcium citrate-
considered. Many patients have Calcium citrate should be the malate is well-absorbed taken with
difficulty swallowing large tablets supplement of choice in patients or without food. 9
or do not want to take multiple with achlorhydria, a condition
tablets to achieve the desired dose common in the elderly. Drawback Coral Calcium
of calcium. 5 associated with the use of calcium
citrate supplements is the need Some calcium supplements
Calcium Carbonate and to take more tablets or capsules are derived from natural sources
Calcium Citrate to make the dose equivalent to such as coral, dolomite (a type
that of calcium carbonate. A of limestone), and oyster shell.
Calcium carbonate is the most requirement for more tablets may Coral calcium (calcium carbonate
common and least expensive form affect compliance. 4 m a t r i x ) i s d e r i ve d f r o m c o r a l
of calcium. Cost is a consideration exoskeletons. It contains primarily
Calcium carbonate is well-
for many patients. A study assessing calcium carbonate (20%) and
absorbed and tolerated in most
the cost of calcium from food and magnesium (10%). However, none
individuals when taken with a meal.
supplements found that calcium of these claims have been validated.
Calcium carbonate supplements
carbonate was the least expensive Calcium from a coral source has
provide greater quantities of
form of calcium, at approximately not been proven to be better than
elemental calcium and therefore
o n e - th i r d t h e c o st of the leas t calcium from other sources. There
require fewer tablets than other
e x p e n s i ve f o o d s o u r c e , w h i c h is also concern that some coral
forms of calcium. Calcium citrate
includes skim milk and calcium- calcium products contain excess
s h ould b e used in individuals
fortified orange juice made from lead. Dolomite supplements may
with suspected achlorhydria,
frozen concentrate. 8 also contain unsafe amounts of lead
inflammatory bowel disease, or
and other heavy metals. 10

Calcium Lactate and
Calcium Gluconate
Calcium lactate and calcium
gluconate are less concentrated
forms of calcium. Calcium lactate
contains 13% elemental calcium,
whereas calcium gluconate contains
only 9% elemental calcium;
therefore, these forms are not
considered practical for clinical
practice. Because calcium lactate
and calcium gluconate contain a
small concentration of elemental
c a l c i u m , m a n y t a b l e t s h a ve t o
be consumed to reach desirable
doses. 5
Calcium lactate and calcium
gluconate are less concentrated
formulae of calcium and are not
practical oral supplements. Study
on hydroxyapatite as a source of
calcium is limited, so this form of
calcium is not recommended.
Calcium products containing
magnesium and vitamin K are also
available. Vitamin K is increasingly
thought to have a role in bone
health. It’s thought to promote
bone formation and reduce calcium
excretion. Preliminary studies
suggest that low vitamin K levels
are related to fracture risk. 5
The maximum dose of elemental
calcium that should be taken at a
time is 500 mg. In clinical practice,
to obtain optimal clinical outcomes
related to calcium supplementation,
the dose of calcium should not
exceed 500 mg at 1 time. It may be
beneficial to supplement in smaller
doses 4 times per day to lower
P T H l e ve l s a n d d ec reas e b on e
resorption. Absorption of calcium
is greatest when taken in a dose of
500 mg or less. 5
Potential Adverse
Effects of Calcium
Supplementation11
Calcium supplements are
generally well tolerated;
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Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017
however, some patients complain
of gastrointestinal symptoms,
including constipation, gas,
flatulence, and bloating.
Hypercalcaemia and hypercalciuria
are uncommon.
Calcium Interaction with
Other Medicinal Products9
Calcium salts may decrease
the absorption of iron, zinc and
strontium ranelate. Consequently,
iron, zinc or strontium ranelate
preparations should be taken
two hours before or after calcium
carbonate. The absorption
of quinolone and tetracycline
antibiotics may be impaired if
administered concomitantly with
calcium. Quinolone antibiotics
should be taken two hours before
or after intake of calcium. If
patient is on a bisphosphonate
this preparation should be
administered at least three hours
before the intake of oral calcium
since gastrointestinal absorption
may be reduced. Thiazide diuretics
reduce the urinary excretion of
calcium. Due to increased risk of
hypercalcaemia, serum calcium
should be regularly monitored
during concomitant use of thiazide
diuretics.
Summary
Calcium is the most obvious and
persistent of the micronutrients,
the fifth most abundant element in
the body. Calcium is an important
mineral component of our diet.
Calcium supplementation can
p l a y a va l u a b l e r o l e i n b o n e
health throughout the lifecycle.
Calcium from carbonate and citrate
should be the forms of select
for supplementation. Calcium
c arbonat e is cost -effect ive b ut
should be taken with meals to
enhance absorption. In patients
with achlorhydria or those
taking gastric acid suppression
103
medications such as H2 blockers or
protein-pump inhibitors. Calcium
citrate is recommended in these
situations. The maximum dose
of elemental calcium that should
be taken at a time is 500 mg. An
adequate calcium intake through
proper selection of calcium salt
is therefore only one of many
measures to ensure a healthy
skeleton.
References
1. Sharon Rady Rolfes, Kathryn Pinna, Ellie
Whitney Understanding Normal and
Clinical Nutrition, Eighth Edition, Chapter
12, Page 418.
2. Dietary guidelines for Indians, ICMR,
National Institute of Nutrition Hyderabad,
second Edition – 2011.
3. Adapted from http://www-users.med.
cornell.edu/~spon/picu/calc/cacalc.htm
accessed on 7 September 2016.
4. Committee to Review Dietary Reference
Intakes for Vitamin D and Calcium, Food
and Nutrition Board, Institute of Medicine.
Dietary Reference Intakes for Calcium
and Vitamin D. Washington, DC: National
Academy Press, 2010.
5. Adapted from Deborah A. Straub. Calcium
Supplementation in Clinical Practice: A
Review of Forms, Doses, and Indications.
Nutrition in Clinical Practice 2007; 22:286–
296.
6. Adapted from Dairy Products: Dairy
Products: the calcium challenge http://
www.jungbunzlauer.com/fileadmin/
content/_PDF/Dairy_Products__the_
Calcium__challenge__Jun02.pdf.
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health benefits of calcium citrate malate: a
review of the supporting science. Adv Food
Nutr Res 2008;54:219-346.
8. Recker RR. Calcium absorption and
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understanding-different-types-of-calcium-
part-2/ access on 10/01/2017
10. Adapted from Pharmacist’s Letter /
Prescriber’s Letter, October 2008,Volume
24, Number 241008 https://unecop2018.
wikispaces.com/file/view/Calcium-Salts.
pdf.
11. A d a p t e d f r o m S P C o f C a l c i c h e w
500mg Chewable Tablets. https://
www.medicines.org.uk/emc/
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access on 7 September 2016.