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Journal of Vita Columbia Volume 2 Issue 1 – Clinical Nutrition

Calcium: An Overview of Metabolism and Homeostasis

January 18th, 2022
How to cite this article:

Azer M and Azer M. Calcium: An Overview of Metabolism and Homeostasis. 2022. Journal of Vita Columbia. 2(1).

Abstract:

Calcium is a mineral found in nature but it is also very vital for processes essential for life in the human body. The human body can’t produce it so it must be ingested. The active form, free ionized calcium in the body must be kept within a strict range otherwise the body begins to enter a diseased state. Whether hypocalcaemia or hypercalcemia, the diseased state of the body presents with several vague signs and symptoms that can lead a physician on a wild goose chase if you aren’t aware of what to look for. In this essay we explore calcium and its effects on the body in normal and abnormal states.

Introduction:

The human body uses many minerals to regulate and help in its many physiological actions. Calcium is one of the most abundant minerals in the body. The word calcium is derived from the word ‘calas’ which means lime in Latin, because it was used by the ancient Romans to prepare lime (CaO) since the first century (2).

The human body contains around 1-1.3 kg of calcium, stored mainly in bones (approximately 99%) and the remaining 1% is distributed as follows: 15% bound to anions, 40% bound to albumin, 45% circulates as free ionized calcium (the active form) (6) .

Calcium is needed in many vital processes in the body; muscle contraction, nerve conduction, blood coagulation, maintenance of cell membranes and release of hormones to name a few uses (2) . A good accumulation of calcium in the bones at early stages in life is the best prevention of age-related bone loss and fractures.

It’s easy to say it is vital to essential processes in the body, and to prattle off a few titles but what exactly does calcium do? Calcium controls nerve excitability (2). The effect is mainly on the peripheral neuromuscular mechanism. It plays a role in maintenance of the integrity of the skeletal muscles (2). It is very essential for maintaining the tone and contractility of cardiac muscles (2). Calcium also takes part in the formation of certain tissue and bones (2).

Metabolism of Calcium

Despite the importance of calcium to the body, it doesn’t produce calcium. we depend on enteral absorption of calcium, around 1000 mg of calcium is ingested daily in a balanced diet. Around 400 mg of that is absorbed through the GIT and the rest is excreted with the stool.

Calcium bioavailability represents the amount of calcium that actually absorbed rather than the amount of calcium in the food (1).  To understand this better, we can use examples; as dairy foods have 30% bioavailability which means if the food label mentions that milk has 300 mg of calcium per cup, the body will absorb around 100 mg of it. On the other hand, leafy green vegetables may have less calcium content but have more bioavailability, for example bok choy has 160 mg of calcium per cup and a high bioavailability of around 50%, that means about 80 mg of calcium will reach the body. (1)

Here is a problem however, some plants have substances that bind to calcium and hence decrease calcium bioavailability such as (oxalates and phytates). Spinach has the largest amount of calcium in all vegetables (around 260 mg per cup) however it is rich in oxalates that bind with calcium making a compound that can’t be absorbed in the GIT. This results in a decrease of the bioavailability to around 5%, so out of the 260 mg of calcium, only 13 mg is absorbed.

The information is not to avoid vegetables since they are rich in many other nutrients, but to organize meals properly, especially if calcium supplements are used. i.e. don’t consume calcium binding food like spinach with calcium supplements or food rich in calcium. (1)

Other factors that affect calcium absorption include following a vegan diet, consuming a large amount of proteins or bowel and digestive diseases (inflammatory bowel disease, lactose intolerance, etc. (7)

Table 1: Recommended Daily Intake of Calcium by Age-Group (8)

Life Stage Recommended Amount
Birth to 6 months 200 mg
 Infants  7–12 months 260 mg
Children 1–3 years 700 mg
Children 4–8 years 1,000 mg
Children 9–13 years 1,300 mg
Teens 14–18 years 1,300 mg
Adults 19–50 years 1,000 mg
Adult men 51–70 years 1,000 mg
Adult women 51–70 years 1,200 mg
Adults 71 years and older 1,200 mg
Pregnant and breastfeeding teens 1,300 mg
Pregnant and breastfeeding adults 1,000 mg

Calcium Level Regulation

The average range of serum calcium is 2.2-2.6 mmol/L in adults. The normal level of ionized calcium 1.17-1.3 mmol/L. Calcium level in plasma depends directly on the balance of bone mineral deposition and resorption, intestinal absorption, and renal excretion (6) . The hormones responsible for regulating these processes include Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, and calcitonin (6).

PTH is secreted by the parathyroid glands as a response to hypocalcaemia, the gland senses the decrease in calcium serum level and secrete parathyroid hormone, the results of which are evident within minutes through:

  1. increase calcium reabsorption through the kidneys
  2. increase calcium absorption in GIT
  3. increase bone resorption
  4. stimulate activation of vitamin D to calcitriol which increases calcium absorption by the intestines. (4)

Vitamin D is produced in the skin by the help of ultraviolet rays from the sunlight. It is then activated to its major circulating form (25(OH) D) and hormonal form (1, 25(OH) 2D) in the liver and kidney, respectively. Its main role is to facilitate intestinal calcium absorption, it also plays a role in bone growth and remodeling by osteoblasts and osteoclasts. Vitamin D has other roles in the body, including reduction of inflammation as well as modulation of such processes as cell growth, neuromuscular and immune function, and glucose metabolism. (5)

Calcitonin is produced from the parafollicular cells in the thyroid gland. It decreases the serum calcium level through:

  1. increases cellular uptake
  2. increases renal excretion
  3. increases osteoblastic activity in bones to build more cells taking more calcium. (4)

In general, parathyroid hormone and vitamin D have a more active role on bone metabolism and remodeling than calcitonin.

Pharmacologic Interactions with Calcium Homeostasis:

There are also many medications affect the level of ionized calcium in blood stream:

There are drugs that increase ionized calcium levels, such as (6): 

  •       Calcium salts
  •       Hydralazine
  •       Lithium
  •       Thiazide diuretics
  •       Thyroxine

There are also drugs that decrease ionized calcium levels, such as (6): 

  •       Heparin
  •       Citrate
  •       Intravenous lipids
  •       Epinephrine
  •       Norepinephrine
  •       Isoproterenol
  •       Alcohol
  •       Ethylenediaminetetraacetic acid

Hypocalcemia:

Outside of the normal range of Calcium we are in one of 2 diseased states, either hypo- or hypercalcemia.

Calcium deficiency is usually due to an inadequate intake of it, therefore when the calcium level drops, the body borrows some from the bones, to be returned to the bones from calcium supplied through the diet (2). If there’s still an inadequate supply of calcium, there will not be enough calcium available to be returned to bones to maintain strong bones and total body health (2).

There are many situations that cause hypocalcaemia: (16)

  • Hypoparathyroidism
  • Pseudo hypoparathyroidism
  • Vitamin D deficiency
  • Renal tubular disease
  • Acute pancreatitis
  • Magnesium depletion (decreased secretion and tissue response to parathyroid hormone)
  • Hungry bone syndrome
  • Septic shock
  • Hyperphosphatemia
  • Massive blood transfusion (> 10 units)

Symptoms of Hypocalcemia

Perhaps two of the most common hypocalcaemia manifestations are perioral numbness or tingling and heart palpitations (arrhythmia). There are, however, a plethora of manifestations that are also quite non-specific but that altogether point us towards a veritable diagnosis.

Muscle Cramping, numbness and tingling in the arms and legs, hyperreflexia, dry Skin, brittle nails, coarse hair, repeated candida infections, cataract, increased PMS symptoms and joint pain are all non-specific on their own but altogether point to hypocalcaemia in the differential diagnosis (2). It is tetany (paresthesia of fingers, feet and perioral region, spasm of facial muscles, carpopedal spasm), heart palpitations (arrhythmia) and osteoporosis (i.e., bone fractures) that force us to investigate a lack of calcium in the body as the primary cause of disease.

There are also of course the famous signs to diagnose hypocalcaemia, Chvostek sign, twitching of facial muscle after tapping on facial nerve, anterior to exterior auditory meatus. Also, Trousseau sign, carpal spasm after inflating blood pressure cuff to 20mmhg above systolic for 3 minutes. (15)

Treatment of Hypocalcemia

Treatment for hypocalcaemia is relatively simple, there are many kinds of calcium supplements.

  • Calcium gluconate used to treat conditions caused by low  calcium  levels such as  osteoporosis, osteomalacia and rickets. It is also used in hypoparathyroidism. (9)
  • Calcium chloride for arrhythmia, hypermagnesemia, calcium channel blocker overdose and beta blocker overdose (10).
  • Calcium acetate to treat hyperphosphatemia in end stage renal failure (11).
  • Calcium citrate used for primary osteoporosis prevention it also protects against renal stones by oxalate chelating and prevent its absorption through the intestine (12).
  • Calcium carbonate, antacid (tums) (13)

Hypercalcemia:

When total serum calcium exceeds 10.4mg/dl ( 2.6 mmol/l ) or ionized calcium is more than 5.2 md/dl (1.3 mmol/l). (14)

Some of the more common causes of hypercalcemia are hyperparathyroidism, vitamin D toxicity, malignancy (paraneoplastic syndrome) in breast cancer, lymphoma, prostate cancer, thyroid cancer, lung cancer, myeloma, and colon cancer). Also, many other diseases can be associated with hypercalcemia such as tuberculosis, sarcoidosis, leprosy and histoplasmosis. (14)

Less commonly, diseases like milk alkali syndrome, familial hypocalciuric hypercalcemia and some conditions like immobility and severe dehydration can cause hypercalcemia. (14)

Symptoms of Hypercalcemia

What should we be on the search for in hypercalcemia? As in hypo, most of the signs and symptoms are vague and non-specific: nausea and vomiting, constipation, abdominal pain, generalized aches, polyuria, muscle weakness, depression, confusion, lethargy and coma. (14)

Hypercalcemia can also lead to kidney stones up to kidney failure. Other complications include osteoporosis, dementia and cardiac arrhythmia which can be fatal.

Treatment of Hypercalcemia

Management of hypercalcemia depends on the severity of each case and whether it’s acute or chronic. Usually it starts with IV saline and diuretics (furosemide). The next step is bisphosphonates. Also hemodialysis or surgical removal of parathyroid glands can be used for refractory cases. (14)

Conclusion:

Calcium is one of the most important minerals in the body, it is essential and vital for life. However it has to be within a specified range as too much or too little of the active form in the blood can be disastrous and possibly fatal. While most of the signs and symptoms of calcium imbalance in the body are vague there are specific warning signs to be on the lookout for as physicians and special tests to determine if calcium imbalance is the culprit.

References:

  1. Calcium – The Nutrition Source., Harvard T.H. Chan – School of Public Health., https://www.hsph.harvard.edu/nutritionsource/calcium/
  2. Piste,Pravina., Calcium and its Role in Human Body., ResearchGate.net., January 2012.,  https://www.researchgate.net/publication/274708965_Calcium_and_its_Role_in_Human_Body
  3. Watson, Stephanie., Calcium: What you should know., WebMD -Vitamins and Supplements., June 2020., https://www.webmd.com/vitamins-and-supplements/calcium
  4.  Lewis III, James L., Overview of Disorders of Calcium Concentration., Merck Manual – Professional Version., April 2020., https://www.merckmanuals.com/en-ca/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/overview-of-disorders-of-calcium-concentration
  5. Vitamin D – Health Professional Fact Sheet., National Institutes of Health- Office of Dietary Supplements., August 2021., https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
  6. Goldberg, Deborah., Calcium, Ionized., Medscape – Laboratory Medicine., Nov. 2019.,  https://emedicine.medscape.com/article/2087469-overview#a1
  7. Mayo Clinic Staff., Calcium and calcium supplements: Achieving the right balance., Healthy Lifestyle – Nutrition and Healthy Eating., November 2020., https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/calcium-supplements/art-20047097
  8. Calcium – Fact Sheet for Consumers., National Institutes of Health – Office of Dietary Supplements. March 2021., https://ods.od.nih.gov/factsheets/Calcium-Consumer/
  9. https://www.webmd.com/drugs/2/drug-8322/calcium-gluconate-oral/details
  10. Calcium Chloride (Rx) – Brand and other names., Medscape – Drug and Diseases., https://reference.medscape.com/drug/cacl-or-cacl-2-calcium-chloride-344432
  11. Calcium Acetate (Rx) – Brand and other names., Medscape – Drug and Diseases., https://reference.medscape.com/drug/eliphos-phoslo-calcium-acetate-344430
  12. Calcium Citrate (Rx) – Brand and other names., Medscape – Drug and Diseases., https://reference.medscape.com/drug/citracal-calcium-citrate-999216
  13. Calcium Carbonate (Rx) – Brand and other names., Medscape – Drug and Diseases., https://reference.medscape.com/drug/tums-calcium-carbonate-341983
  14. Lewis III, James L., Hypercalcemia. MSD Manual Professional version. April 2020., https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypercalcemia
  15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681085/
  16. https://www.healthline.com/health/calcium-deficiency-disease#causes
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