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Calcium

It is  involved in skeletal mineralization, contraction of muscles, the transmission of nerve impulse, blood clotting,  U.S. led contraction, and secretion of hormones.

 

Calcium is mostly present in the extracellular fluid. 

Approximately 50% of total calcium is ionized and biologically active.

The remainder is bound to albumin and immunoglobulins in a pH dependent manner or complexed with ions.

Diet is the predominant source of calcium. 

Typical Western diet has 200-400 mg of calcium per day.

Average adult has 1 kg of calcium of which 99% is in the form of hydroxyapatite in the skeleton and 1% in soft tissues and extracellular spaces.

Necessary for neuromuscular function, blood coagulation, and intracellular signaling.

Normal circulating levels 9-10 mg/dL [2.25-2.5 mmol/L].

About 50-60% of calcium is bound to plasma albumin.

Approximately half of serum calcium is present as free ions, and approximately 10 percent is complexed with phosphate, carbonate, and oxalate.

Each 0.1 g/dL decrease in serum albumin level is associated with a 0.8 mg/dL [0.2 mmol/L] drop in serum calcium concentration.

Absorption of calcium in the intestine is primarily under the control of the hormonally active form of vitamin D, which is 1,25-dihydroxy vitamin D3. 

 

Intestinal calcium absorption decreases with age.

In communities with calcium-rich water supply have a lower incidence of cardiovascular events.

There is an upper trend in cardiovascular event rates including myocardial infarction and sudden death in postmenopausal women who receive calcium supplementation, resulting in higher blood calcium levels.

Under the regulation of parathyroid hormone, 1, 25-dihydroxy vitamin D, and ionized calcium, as well as their respective receptors.

Parathyroid hormone also regulates calcium secretion in the distal tubule of kidneys.

Parathyroid hormone and vitamin D regulate skeletal mobilization, kidney excretion, and intestinal absorption of calcium to achieve calcium homeostasis.

 

Around 250 mmol of calcium ions are filtered into the glomerular filtrate per day: Most of this (245 mmol/d) is reabsorbed from the tubular fluid.

 

About 5 mmol/d are excreted in the urine. 

 

This reabsorption of calcium ions occurs throughout the tubule.

 

Most, 60-70% of calcium ions are reabsorbed in the proximal tubule.

 

Circulating parathyroid hormone influences the reabsorption only that occurs in the distal tubules and the renal collecting ducts.

 

More importantly is PTH’s effect on the kidney is its inhibition of the reabsorption of phosphate from the tubular fluid, resulting in a decrease in the plasma phosphate concentration. 

 

Phosphate ions form water-insoluble salts with calcium. 

A decrease in the phosphate concentration of the blood plasma increases the amount of calcium that is ionized.

 

Calcitonin acts on bone cells to increase the calcium levels in the blood.

Both high and low serum calcium levels are associated with increased mortality.

Inadequate intake depletes or limits bone mass which is the body’s calcium reserve causing or aggravating osteoporosis.

Unabsorbed gut calcium averages 90% of intake complexes and neutralizes potential harmful byproducts of digestion such as free fatty acids, bile acids and oxalic acid.

Most individuals need 1,000 mg of calcium daily, but men over the age of 65 years and postmenopausal women need 1,500 mg, that is equal to 5 eight oz glasses of milk or five cups of yogurt each day.

Supplementation with lower daily dose of vitamin D (400 IU of vitamin D3 orvles) and calcium 1000 mg calcium carbonate do not preven fractures in postmenopausal women (USPSTF).

Studies using supplements including both calcium and vitamin D reveal no benefit in reducing the number of non-vertebral fractures, and the risk of hip fracture was greater among persons who received calcium supplements than among those who received placebo in a meta-analysis of 6740 patients.

In the above study i in 273 women who take such doses will develop kidney stones by 7 years.

Excessive ingestion of calcium linked to kidney stones, hypercalcemia, hypercalcinuria, vascular and soft tissue calcifications, unfavorable interactions with zinc, iron, cardiovascular disease and constipation.

Dietary sources of calcium include milk and yogurt, but also include green leafy veggies like collard greens, legumes like black-eyed peas, tofu, almonds, and orange juice.

Extracellular calcium homeostasis is tightly controlled and is dependent on the balance between dietary intake, intestinal absorption, renal excretion, and bone remodeling.

Calcium ions are one of the most ubiquitous signal transduction molecules in almost all cells.

Calcium ions are important in regulating cardiac physiology and electrophysiology.

There are 10000 fold calcium ion gradient across the sarcolemma of the cardiomyocyte.

There is an intracellular calcium concentration of approximately 100 nmols and an extracellular calcium concentration of approximately 2 millimoles in a cardiomyocyte.

Low serum calcium levels are associated with an increased risk of sudden cardiac death in the community and in patients on dialysis.

Intracellular calcium concentrations are regulated in cardiomyocytes, and are the key determinants in cardiac excitation – contraction coupling.

Calcium is in essential cation for myocardial action potential and excitation – contraction coupling of cardiac muscle.

The inability to maintain a low intracellular calcium is associated with cardiac pathology and is known to cause arrhythmias, and mediates sudden cardiac death.

Intracellular calcium overload is associated with acute myocardial ischemia, cardiomyopathies, congestive heart failure, digitalis toxicity, catecholaminergic polymorphic ventricular tachycardias, and ischemia/reperfusion.

Hypocalcemia and hypercalcemia represent conditions of disordered calcium homeostasis and are associated with cardiovascular abnormalities.

Hypercalcemia is associated with hypertension, with left ventricular hypertrophy, vascular calcifications, shortened QT interval and arrhythmias.

Hypocalcemia is associated with heart failure, prolonged QT intervals and life-threatening cardiac arrhythmias.

More than 50% of US women middle-aged or older take calcium supplements.

The use of calcium supplements is associated with increased risk of cardiovascular disease (Boland MJ at al).

In a longitudinal prospective cohort study of 61,433 women followed for up to 19 years assessing women’s diet and supplement use found that women who consume more than 1400 mg of calcium daily had a higher rate of death from all causes compared to women who consume between 600-1000mg daily(Michaelson K et al).

In the above study women who consumed more than 1400 mg calcium daily had an increased risk of death from cardiovascular disease and ischemic heart disease, but not stroke.

The above study found that women who had high dietary calcium O’Grady 1400 mg today and who also took calcium supplements had further increasing cardiovascular risks.

In a prospective study of 388,229 men and women aged 50-71 years from the National Institutes of Health-AARP Diet and Help Study found that high intake of supplemental calcium was associated with excess risk of cardiovascular deaths in men but not in women.

The US Preventative Services Task Force recommends against using supplements of vitamin D and calcium to prevent fractures: in the review of six randomized trials there was no evidence of benefit from taking 400 international units of vitamin d3 and 1000 mg of calcium daily, but one in every 273 women who took supplements for at least seven years developed kidney stones.

In the US the recommended daily allowance for calcium is 1000 mg per day for children 4-8 years of age.

Among girls in the early stages of puberty, Calcium balance is positive with an intake of less than 400 mg per day, and among children 4-8 years of age, calcium intake is uncorrelated with bone mineral density.

In a study of nearly 10,000 men and women calcium intake was unrelated to bone mineral density at the hip (Bischoff-Ferrari HA).

Supplementation of calcium supplementation in children show a small or no increase in bone mineral density, and increases in the number do not persist after discontinuation, providing no evidence of high calcium and intake is needed.

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