By Susan Skanderup Jensen
Calcium facts
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Soft grey alkaline earth metal
Symbol Ca
Number 20
Group II
Divalent cation
Atomic weight 40 g/mol
Single oxidation state +2
Fifth most abundant element in Earth´s crust
Essential for living organisms
Calcium history
• Latin calx or calcis meaning ”lime”
• Known as early as first century when ancient
Romans prepared lime as calcium oxide
• Isolated in 1808 by Englishman Sir Humphrey
Davy
- Electrolyzed a mixture of lime & mercuric acid
• In 1883 demonstrated Sydney Ringer the
biological significance of calcium
- Frog hearts needed the presence of calcium in the
bathing solution in order to continue beating
Calcium occurrence
In nature
• Does not exist freely
• Occurs mostly in soil systems as limestone
(CaCO3), gypsum (CaSO4*2H2O) & fluorite (CaF2)
In the body
• The most abundant mineral
• Average adult body contains app. 1 kg
• 0,1 % in the extra cellular fluid
• 1 % in the cells
• The rest (app. 99 %) in the skeleton
(Bones can serve as large reservoirs, releasing calcium when
extracellular fluid concentration decreases and storing excess
calcium)
Measuring calcium
• Atomic absorption spectrometry (AAS) can measure total
amount of Ca2+ in tissue
• Fluorescent dyes can be used to measure Ca2+ in vivo
• Calcium sensor (GFP-based) fluorescent protein
“cameleon” is non invasive and can be targeted to various
cellular compartments – enabling a study of spatial and
organellar aspects of calcium homeostasis
• Neutron activation analysis enables total body calcium to
be measured in living persons
• Bone mineral content (BMC) and bone mineral density
(BMD) are used as indicators of calcium insufficiency and as
predictors of increased risk of fracture, when compared to a
reference range, adjusted for age and gender
Calcium functions
• Major structural element in the vertebrate
skeleton (bones and teeth) in the form of
calcium phosphate (Ca10(PO4)6(OH)2
known as hydroxyapatatite
• Key component in the maintenance of the
cell structure
• Membrane rigidity, permeability and
viscosity are partly dependent on local
calcium concentrations
Calcium functions (Bone)
• Osteoclasts (bone cells)
remodel the bone by
dissolving or resorbing
bone
• Osteoblasts (bone
forming cells) synthesize
new bone to replace the
resorbed bone
- Found on the outer
surfaces of the bones
and in the bone cavities
Calcium functions
Plays important regulatory roles in the body
A passive role:
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As a cofactor for many enzymes (e.g. Lipase) and proteins
As component in the blood clotting cascade
An active role: as an intracellular signal
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In the relaxation and constriction of blood vessels
In cell aggregation and movement
In muscle protein degradation
In secretion of hormones as insulin
In cell division
In nerve impulse transmission
Interactions
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Phosphate: ↓ calcium excretion in the urine
Caffeine: ↑ urinary and fecal excretion of calcium
Sodium: ↑ sodium intake, ↑ loss of calcium in urine
Dietary constituents: Phytic acid can reduce
absorption of calcium by forming an insoluble salt
(calcium phytate)
• Iron: calcium might have inhibitory effect on iron
absorption
Absorption and excretion
• Usual intakes is 1000 mg/day
• About 35 % is absorbed (350
mg/day) by the intestines
• Calcium remaining in the intestine
is excreted in the feces
• 250 mg/day enters intestine via
secreted gastrointestinal juices and
sloughed mucosal cells
• 90 % (900 mg/day) of the daily
intake is excreted in the feces
• 10 % (100 mg/day) of the ingested
calcium is excreted in the urine
• Calcium must be in a soluble and
ionized form before it can be
absorbed
Absorption and excretion factors
• Absorption increased by:
• Excretion increased by:
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Body need
Vitamin D
Protein
Lactose
Acid medium
Low parathyroid hormone (PTH)
High extracellular fluid volume
High blood pressure
Low plasma phosphate
Metabolic alkalosis
• Absorption decreased by: • Excretion decreased by:
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Vitamin D deficiency
Calcium-phosphorus imbalance
Oxalic acid
Phosphorous
Dietary fiber
Excessive fat
High alkalinity
Also stresses and lack of exercise
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High parathyroid hormone
Low extracellular fluid volume
Low blood pressure
High plasma phosphate
Metabolic acidosis
Vitamin D3
Metabolism
• Factors involved in calcium metabolism
Transport mechanism
Active and passive transport mechanisms
• Active: is a saturable, transcellular
process which involves calbindin (calciumbinding protein) – regulated by the active
form of vitamin D
• Passive: is a nonsaturable, paracellular
low efficiency process, which is not
affected by calcium status or parathyroid
hormone
• Both processes occur throughout the small
intestine
Regulation
Vitamin D, parathyroid hormone and calcitonin
• Vitamin D (in active form)
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Has several effects on the intestine and kidneys that increase
absorption of calcium and phosphate into the extracellular fluid
Important effects on bone deposition and bone absorption
• Parathyroid hormone (PTH)
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Provides powerful mechanism for controlling extracellular calcium
and phosphate concentrations by regulating intestinal reabsorption,
renal excretion and exchange between the extracellular fluid and
bone of the two ions
• Calcitonin (a peptide hormone secreted by the thyroid gland)
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Tends to decrease plasma calcium concentration
In general, has effects opposite to those of PTH (quantitative role is
far less than that of PTH in regulating Ca ion concentration)
Regulation
Activation of vitamin D3
- Cholecalciferol formed
in the skin by sun
- Converted in liver
(feedback effect)
- 1,25 DHCC formation in
kidney
- Controlled by PTH
- Plasma calcium
concentration
inversely regulates
1,25 DHCC
Regulation
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Compensatory responses to decreased plasma ionized calcium
concentration mediated by PTH & vitamin D
PTH regulates through 3 main effects:
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By stimulating bone resorption
By stimulating activation of vitamin D → ↑ intestinal Ca reabsorption
By directly increasing renal tubular calcium reabsorption
Adequate daily intake (AI)
Life Stage
Age
Males (mg/day)
Females (mg/day)
Infants
0-6 months
210
210
Infants
7-12 months
270
270
Children
1-3 years
500
500
Children
4-8 years
800
800
Children
9-13 years
1,300
1,300
Adolescents
14-18 years
1,300
1,300
Adults
19-50 years
1,000
1,000
Adults
51 years and older
1,200
1,200
Pregnancy
18 years and younger
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1,300
Pregnancy
19 years and older
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1,000
Breastfeeding
18 years and younger
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1,300
Breastfeeding
19 years and older
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1,000
Calcium sources
• Rich calcium sources (600-961mg/100g)
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Cheese
Wheat-soy flour
Blackstrap molasses
• Good sources (122-354mg/100g)
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Dairy products as milk, yoghurt, sour cream, ice cream
Green leafy vegetables as collard, kale and raw turnip
Fish as trout, salmon and sardines
Almonds, brazil nuts, dried figs, hazel nuts
Also soybean flour and cottonseed flour
• Poor sources
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Most fresh fruit
Deficiency
• A negative calcium balance occurs when net
calcium absorption is unable to replace losses
• The most dramatic symptoms are manifested in
the teeth and bones of young humans and
animals → stunted growth, poor quality of bones
and teeth and malformation of bones
• Hypocalcaemia (low serum calcium levels in the
blood cause the nervous system to become more
excited)
• Osteoporosis (bone resorption exceeds formation)
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Occurs particularly in women. Increases in bone loss and
osteoporotic fracture with age is a consequence of calcium
deficiency
• Osteomalacia, tetany and kidney stones are other calcium
related diseases
Causes of deficiency
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Low Ca2+ intake
Vitamin D deficiency
Insufficiency or failure of parathyroid gland
Chronic kidney failure
Low blood magnesium level (in cases with
severe alcoholism)
• Diet high in phytate
Toxicology
• The UL for calcium is 2500 mg/day
• MAS (Milk alkali syndrome)
- Rare and potentially life threatening
condition in individuals consuming large
quantities of calcium and alkali
- Characterized by renal impairment,
alkalosis and hypercalcemia: cause
progressive depression of the nervous
system
Human health studies
• Resent studies showed
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Calcium may play a substantial contributing role in reducing
the incidence of obesity and prevalence of the insulin
resistance syndrome
High calcium intake is associated with a plasma lipoproteinlipid profile predictive of a lower risk of coronary heart
disease compared with a low calcium intake
Dairy product intake (with recommended calcium levels)
protect women consuming oral contraceptives from spine
and hip bone loss
Children who avoid drinking cow milk have low dietary
calcium intakes and poor bone health
Conclusion
• Calcium is essential!!!
• A important mineral for human health
• Must meet adequate daily intake in order
to maintain a healthy skeleton
• A very exciting area for research
Additional slide
• Interaction with iron
• An absorption depressing effect of calcium on iron
absorption has been clearly demonstrated in single-meal
studies and short-term diet intervention studies (Hallberg et
al. 1991)
• An addition of 150 mg of calcium to bread or a hamburger
meal reduced iron absorption by 50 %. The interaction is
suggested to take place within the mucosal cells as both
haem and nonhaem iron is affected (Hallberg et al. 1993)
• Long term calcium supplementation studies have failed to
demonstrate any negative effect on iron status (Ilich-Ernst et
al. 1998; Kalkwarf & Harrast, 1998; Minihane & FairweatherTait, 1998; Sokoll & Dawson-Hughes, 1992; Yan et al, 1996)