Calcium

1. Calcium By Susan Skanderup Jensen

2. 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

3. 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

4. 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)

5. 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

6. 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

7. 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

8. Calcium functions Plays important regulatory roles in the body A 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

9. 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

10. 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

11. 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 Absorption and excretion factors

12. Metabolism • Factors involved in calcium metabolism

13. 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

14. 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)

15. 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

16. 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

17. Adequate daily intake (AI)

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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)