By Susan Skanderup Jensen

Calcium facts

• 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 bodyA passive role: - 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 - 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

• 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:- Body need- Vitamin D- Protein- Lactose- Acid medium• Absorption decreased by:- Vitamin D deficiency- Calcium-phosphorus imbalance- Oxalic acid- Phosphorous- Dietary fiber- Excessive fat- High alkalinity- Also stresses and lack of exercise

• Excretion increased by:- Low parathyroid hormone (PTH)- High extracellular fluid volume- High blood pressure- Low plasma phosphate- Metabolic alkalosis• Excretion decreased by:- 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 (calcium-binding 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)- 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)- 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)

- 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)

RegulationActivation 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

• Compensatory responses to decreased plasma ionized calcium concentration mediated by PTH & vitamin D

• PTH regulates through 3 main effects:- 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 -  1,300 

Pregnancy  19 years and older -  1,000 

Breastfeeding  18 years and younger -  1,300 

Breastfeeding  19 years and older -  1,000

Calcium sources

• Rich calcium sources (600-961mg/100g)- Cheese

- Wheat-soy flour

- Blackstrap molasses

• Good sources (122-354mg/100g) - 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- 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)- 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

• 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- 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 lipoprotein-lipid 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 & Fairweather-Tait, 1998; Sokoll & Dawson-Hughes, 1992; Yan et al, 1996)