Tuesday 4 October 2011

Calcium metabolism

Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcemia or hypocalcemia, both of which can have important consequences for health.

Calcium pool and distribution in the body

Wikipedia. Calcium is the most abundant mineral in the human body. The average adult body contains in total approximately 1 kg, 99% in the skeleton in the form of calcium phosphate salts. The extracellular fluid (ECF) contains approximately 22.5 mmol, of which about 9 mmol is in the serum. Approximately 500 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours.

Medpedia. Calcium, the most abundant mineral in the human body, has several important functions. More than 99% of total body calcium is stored in the bones and teeth where it functions to support their structure. The remaining 1% is found throughout the body in blood, muscle, and the fluid between cells. Calcium is needed for muscle contraction, blood vessel contraction and expansion, the secretion of hormones and enzymes, and sending messages through the nervous system. A constant level of calcium is maintained in body fluid and tissues so that these vital body processes function efficiently.
Bone undergoes continuous remodeling, with constant resorption (breakdown of bone) and deposition of calcium into newly deposited bone (bone formation). The balance between bone resorption and deposition changes as people age. During childhood there is a higher amount of bone formation and less breakdown. In early and middle adulthood, these processes are relatively equal. In aging adults, particularly among postmenopausal women, bone breakdown exceeds its formation, resulting in bone loss, which increases the risk for osteoporosis (a disorder characterized by porous, weak bones).

Calcium absorption

Medpedia. Calcium is a naturally occurring mineral that is needed by the body to build and maintain strong bones and teeth, enable muscle contraction, facilitate chemical reactions in cells, regulate blood vessel size, and send messages through the nervous system. A constant level of calcium is maintained in body fluid and tissues so that these vital body processes function efficiently.
Because calcium is not made in the body, it must be absorbed from a person's dietary intake. Calcium is shed from the body in skin, nails, hair, sweat, urine, and feces. When a person does not get enough calcium through their diet, the body must break down bone to obtain the mineral.
Throughout life, bones go through a process known as remodeling, in which small amounts of old bone are removed and new bone is formed in its place. Generally, after age 35, more bone is lost than gained. Bone loss accelerates after menopause. Calcium from food or supplements is absorbed in the intestines. Vitamin D is necessary for this absorption. Some substances interfere with calcium absorption.

Calcium absorption refers to the amount of calcium that is absorbed from the digestive tract into the body's circulation. Calcium absorption can be affected by the calcium status of the body, vitamin D status, age, pregnancy and plant substances in the diet. The amount of calcium consumed at one time such as in a meal can also affect absorption. For example, the efficiency of calcium absorption decreases as the amount of calcium consumed at a meal increases.

Factors affecting calcium absorption

Age

Net calcium absorption can be as high as 60% in infants and young children, when the body needs calcium to build strong bones. Absorption slowly decreases to 15-20% in adulthood and even more as one ages. Because calcium absorption declines with age, recommendations for dietary intake of calcium are higher for adults ages 51 and over.

Vitamin D

Vitamin D is vital for efficient calcium absorption. Without sufficient vitamin D, the small intestine absorbs ~15% of dietary calcium, while with sufficient vitamin, the small intestine absorbs ~30% of dietary calcium. Calcium absorption during growth, lactation, and pregnancy can increase to 80% of dietary calcium. Vitamin D is a fat-soluble vitamin that is obtained either from food or it can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation. When exposure to UVB radiation is insufficient for the synthesis of adequate amounts of vitamin D in the skin, adequate intake of vitamin D from the diet is essential for health. The Office of Dietary Supplement's vitamin D fact sheet provides more information.

Pregnancy

Current calcium recommendations for nonpregnant women are also sufficient for pregnant women because intestinal calcium absorption increases during pregnancy. For this reason, the calcium recommendations established for pregnant women are not different than the recommendations for women who are not pregnant.

Foods

Phytic acid and oxalic acid, which are found naturally in some plants, and thus foods, may bind to calcium and prevent it from being absorbed optimally. These substances affect the absorption of calcium from the plant itself, not the calcium found in other calcium-containing foods eaten at the same time. Examples of foods high in oxalic acid are spinach, collard greens, sweet potatoes, rhubarb, and beans. Foods high in phytic acid include whole grain bread, beans, seeds, nuts, grains, and soy isolates. Although soybeans are high in phytic acid, the calcium present in soybeans is still partially absorbed. Fiber, particularly from wheat bran, could also prevent calcium absorption because of its content of phytate. However, the effect of fiber on calcium absorption is more of a concern for individuals with low calcium intakes. The average American tends to consume much less fiber per day than the level that would be needed to affect calcium absorption.

Wikipedia. About 25 mmol of calcium enters the body in a normal diet. Of this, about 40% (10 mmol) is absorbed in small intestine, and 5 mmol leaves the body in feces, netting 5 mmol of calcium a day. Calcium is absorbed across the intestinal brush border membrane, passing through ion channels such as TRPV6. Calbindin is a vitamin D-dependent calcium-binding protein inside intestinal epithelial cells which functions together with TRPV6 and calcium pumps (PMCA1) in the basal membrane to actively transport calcium into the body. The active transport occurs primarily in the duodenum when calcium intake is low, and passive paracellular diffusion occurs in the ileum and jejunum, independent of Vitamin D, when calcium intake is high.

Calcium excretion

Wikipedia. The kidney excretes 250 mmol a day in pro-urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d. In addition to this, the kidney processes Vitamin D into calcitriol, the active form that is most effective in assisting intestinal absorption. Both processes are stimulated by parathyroid hormone. 

This refers to the amount of calcium eliminated from the body in urine, feces and sweat. Calcium excretion can be affected by many factors including dietary sodium, protein, caffeine and potassium.

Factors affecting calcium excretion

Sodium and protein

Typically, dietary sodium and protein increase calcium excretion as the amount of their intake is increased. However, if a high protein, high sodium food also contains calcium, this may help counteract the loss of calcium.

Potassium

Increasing dietary potassium intake (such as from 7-8 servings of fruits and vegetables per day) in the presence of a high sodium diet (>5100 mg/day, which is more than twice the Tolerable Upper Intake Level of 2300 mg for sodium per day) may help decrease calcium excretion particularly in postmenopausal women.

Caffeine

Caffeine has a small effect on calcium absorption. It can temporarily increase calcium excretion and may modestly decrease calcium absorption, an effect easily offset by increasing calcium consumption in the diet. One cup of regular brewed coffee causes a loss of only 2-3 mg of calcium easily offset by adding a tablespoon of milk. Moderate caffeine consumption (1 cup of coffee or 2 cups of tea per day) in young women who have adequate calcium intakes has little to no negative effects on their bones.

Other factors

  • Phosphorus: The effect of dietary phosphorus on calcium is minimal. Some researchers speculate that the detrimental effects of consuming foods high in phosphate such as carbonated soft drinks is due to the replacement of milk with soda rather than the phosphate level itself.
  • Alcohol: Alcohol can affect calcium status by reducing the intestinal absorption of calcium. It can also inhibit enzymes in the liver that help convert vitamin D to its active form which in turn reduces calcium absorption. However, the amount of alcohol required to affect calcium absorption is unknown. Evidence is currently conflicting whether moderate alcohol consumption is helpful or harmful to bone.
In summary, a variety of factors that may cause a decrease in calcium absorption and/or increase in calcium excretion may negatively affect bone health.

Normal calcium levels in blood/serum

Total calcium comprises protein-bound calcium and free calcium ions in blood plasma (measured as serum calcium). Free calcium ions mean (refer to) ionized calcium which are not bound to plasma proteins.

The serum level of calcium is closely regulated with a normal total calcium of 2.2-2.6 mmol/L (9-10.5 mg/dL) and a normal ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL).

The amount of total calcium varies with the level of serum albumin, a protein to which calcium is bound.

The biologic effect of calcium is determined by the amount of ionized calcium, rather than the total calcium.

Ionized calcium does not vary with the albumin level, and therefore it is useful to measure the ionized calcium level when the serum albumin is not within normal ranges, or when a calcium disorder is suspected despite a normal total calcium level.

Corrected calcium level

Serum is preferred for blood biochemistry determinations. These blood analytes are determined using serum: serum total calcium, serum albumin.  

Corrected calcium is determined using a formula. Calcium exists in 2 states in the body - bound to protein (mostly albumin) and free ionized calcium. Total calcium is the sum of protein-bound calcium plus free ionized calcium.


(i) Determination of calcium when albumin level is abnormal

One can derive a corrected calcium level when the albumin level is abnormal. This is to make up for the change in total calcium due to the change in albumin-bound calcium, and gives an estimate of what the calcium level would be if the albumin were within normal ranges.
Corrected calcium (mg/dL) = measured total calcium (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level in g/dL.
In other words, each 1 g/dL decrease of albumin will decrease 0.8 mg/dL in measured serum calcium and thus 0.8 must be added to the measured Calcium to get a corrected Calcium value.
Or: Corrected calcium (mmol/L) = measured total calcium (mmol/L) + 0.02 (40 - serum albumin [g/L]), where 40 represents the average albumin level in g/L
In other words, each 1 g/L decrease of albumin, will decrease 0.02 mmol/L in measured serum calcium and thus 0.02 must be added to the measured value to take this into account and get a corrected calcium.

(ii) Determination of calcium when albumin level is low

When there is hypoalbuminemia (a lower than normal albumin), the corrected calcium level is higher than the total calcium. 

The role of bone

Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Calcium release from bone is regulated by parathyroid hormone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin.

Low calcium intake may also be a risk factor in the development of osteoporosis. In one meta-analysis, the authors found that fifty out of the fifty-two studies that they reviewed showed that calcium intake promoted better bone balance. With a better bone balance, the risk of osteoporosis is lowered.


Sources:
Calcium metabolism in Wikipedia
Calcium in Medpedia

0 comments: