Calcium

Calcium is a mineral that constitutes a significant portion of bone tissue and is essential for the structural integrity of bones and teeth. It also serves as a signaling molecule in various cellular processes, including muscle contraction, nerve transmission, and hormone secretion.

Within the body, calcium plays a pivotal role in muscle contraction, including the heartbeat, nerve impulse transmission, blood clotting, and cell signaling. Additionally, it contributes to bone health by providing structural support and strength, regulating bone turnover, and maintaining bone density throughout life.

Calcium is abundant in various dietary sources, including dairy products such as milk, cheese, and yogurt, as well as leafy green vegetables like kale and broccoli, fortified foods such as orange juice and cereals, and certain fish with edible bones like sardines and salmon.

This article will provide an overview of the functions of calcium, recommended intake and indications for supplementation, appropriate testing options, and natural ways to optimize calcium levels.  

Definition and Function of Calcium

Definition of Calcium: What is Calcium?  [2., 11.]

Calcium is a mineral vital for bone formation and metabolism.  It is primarily stored as calcium hydroxyapatite in bones and teeth, contributing to their strength. 

Beyond skeletal support, calcium plays pivotal roles in muscle function, nerve transmission, hormonal secretion, and intracellular signaling throughout the body. 

Regulated by the parathyroid hormone (PTH)–vitamin D system, calcium metabolism involves complex feedback loops to maintain tightly regulated serum calcium levels. Absorption occurs via active transport and passive diffusion in the intestines, regulated by calcitriol and the vitamin D receptor. 

Urinary and fecal excretion balance calcium levels, with nearly 98 percent of filtered calcium reabsorbed by the kidneys. However, factors such as aging, hormonal fluctuations, and dietary intake influence calcium absorption and excretion, impacting overall calcium balance and homeostasis.

Calcium has intracellular and intercellular functions, with serum calcium existing in protein-bound, chelated, and free forms. Free calcium, constituting 51% of serum calcium, is vital for physiological processes. 

Hormonal regulation via parathyroid hormone (PTH) and calcitonin maintains calcium homeostasis by influencing calcium transport in various organs. 

Intracellularly, ionized calcium is crucial for muscle contraction, including skeletal, smooth, and cardiac muscle function, facilitated by intricate mechanisms involving sarcoplasmic reticulum release and calcium channel activation. 

Additionally, ionized calcium serves microbiological roles and modulates enzyme activity and cellular responses to hormones.

Calcium Balance: What is Calcium Balance?  [2.]

Calcium balance is determined by the difference between total intake and urinary/endogenous fecal excretion, reflecting calcium retention or loss.

Positive balance indicates calcium accretion, neutral balance suggests bone maintenance, and negative balance signifies bone loss.

Balance studies assess calcium intake and output, typically through urine and fecal analysis, but they have limitations in precision and are generally cross-sectional.

A positive calcium balance is crucial during growth stages, while later in life, menopause and aging lead to a net loss of calcium due to increased bone resorption.

Calcium Across the Human Lifespan  [2.]

Throughout the lifespan, calcium plays critical roles in various stages of development and health maintenance. 

In infancy, calcium is essential for bone growth and development, with breast milk and formula serving as primary sources. 

Childhood and adolescence are marked by rapid bone accretion, especially during puberty, necessitating increased calcium intake for optimal skeletal health. Young adulthood sees consolidation of bone mass, with peak bone mass achieved in early adulthood. 

In older adults bone loss becomes a concern, particularly in postmenopausal women due to estrogen decline. During pregnancy, maternal calcium intake is crucial for fetal skeletal development, while lactation requires calcium mobilization from maternal stores to support breast milk production. 

Despite physiological adaptations, adequate calcium intake remains vital for maintaining bone health across all life stages.

Functions of Calcium: What Does Calcium Do in the Body?  [2., 11.]

Calcium serves many diverse roles in the human body that are essential for overall health and wellness.

Calcium is an Integral Component of Skeleton:

• Critical for tissue rigidity, strength, and elasticity.
• Provides mineral homeostasis and serves as a reservoir.
• Marrow cavity serves as a site for hematopoietic cells and immune system.

Calcium Functions as an Intracellular Messenger:

• Calcium is essential for mediating vascular contraction, muscle function, nerve transmission, and hormonal secretion.

Calcium Promotes Bone Formation and Remodeling:

• Bone is composed of calcium hydroxyapatite and organic matrix, so calcium is an essential component of strong bones.
• It is part of the organic matrix crucial for structure and function.
• Bones development occurs through intramembranous or endochondral bone formation.
• Mineralization is facilitated by a complex process involving calcium and phosphate.

Physiological Importance of Calcium in Skeletal Homeostasis:

• Calcium is a vital part of skeletal remodeling through bone resorption and formation.
• Role of physical activity in skeletal health.

Adequate Calcium is Essential in Pregnancy and Lactation:

• The creation of a new human skeleton requires calcium, as does the production of breast milk.  

Additional functions of calcium continue to be elucidated.  For example, altered calcium signaling has been implicated in attention-deficit hyperactivity disorder (ADHD), with preclinical studies showing impaired intracellular calcium handling in ADHD models like the spontaneously hypertensive rat (SHR) and G-protein subunit Gβ5 knockout mice. 

Recent research suggests that GNB5 may enhance store-operated calcium entry (SOCE) through its interaction with the ER calcium sensor STIM1, highlighting a potential role in regulating calcium homeostasis in ADHD. Further studies are needed to elucidate the precise mechanisms involved.   [4.] 

Dietary Sources of Calcium  [6.]

Calcium is available in the diet in foods and supplements.  Additionally, some foods are fortified with additional calcium.

Plant-based sources of calcium:

• Tofu, firm, made with calcium sulfate, ½ cup - 253 mg
• Soymilk, calcium fortified, 1 cup - 299 mg
• Spinach, boiled, drained, ½ cup - 123 mg
• Kale, fresh, cooked, 1 cup - 94 mg
• Chia seeds, 1 tablespoon - 76 mg
• Chinese cabbage (bok choi), raw, shredded, 1 cup - 74 mg
• Turnip greens, fresh, boiled, ½ cup - 99 mg
• Beans, pinto, canned, drained, ½ cup - 54 mg
• Tortilla, corn, one, 6” diameter - 46 mg
• Kale, raw, chopped, 1 cup - 24 mg
• Broccoli, raw, ½ cup - 21 mg

Animal-based sources of calcium:

• Yogurt, plain, low fat, 8 ounces - 415 mg
• Orange juice, calcium fortified, 1 cup - 349 mg
• Mozzarella, part skim, 1.5 ounces - 333 mg
• Sardines, canned in oil, with bones, 3 ounces - 325 mg
• Milk, nonfat, 1 cup - 299 mg
• Milk, whole (3.25% milk fat), 1 cup - 276 mg
• Salmon, pink, canned, solids with bones, 3 ounces - 181 mg
• Cottage cheese, 1% milk fat, 1 cup - 138 mg
• Frozen yogurt, vanilla, soft serve, ½ cup - 103 mg
• Sour cream, reduced fat, 2 tablespoons - 31 mg
• Apple, golden delicious, with skin, 1 medium - 10 mg

Recommended Intake And Supplementation

RDA of Calcium: How Much Calcium Should I Get?

The RDA of calcium changes throughout the human lifespan.  

Children and adolescents should get between 1000-1300 mg of calcium a day.  Adult men and women are recommended to get 1000 mg of calcium a day, although that recommendation rises to 1200 mg of calcium daily for postmenopausal women, and men and women over 70 years.  

The recommendation for calcium intake in pregnancy and lactation is 1000 mg a day.  

Indications for Supplementation: Should I Take a Calcium Supplement?

This is an important conversation to have with a licensed health professional who can order testing including serum calcium levels and a bone density assessment.  With that information, a personalized plan including supplementation and appropriate followup can be determined.  

General indications for calcium supplementation may include the following causes of hypocalcemia, or low calcium levels:  [1.]

PTH Deficiency:

• Postsurgical hypoparathyroidism, especially after thyroidectomy or parathyroidectomy.
• Autoimmune hypoparathyroidism, including autoimmune polyglandular syndrome type I (APECED).
• Abnormal parathyroid gland development, associated with genetic disorders like DiGeorge syndrome.
• Parathyroid gland destruction due to infiltrative diseases, chemotherapy, or radiation therapy.

High PTH Levels:

• Secondary hyperparathyroidism due to vitamin D deficiency, chronic kidney disease, or pseudohypoparathyroidism.

Other Causes:

• Osteoporosis or low bone density
• Osteopenia
• Hypocalcemia (low blood calcium levels)
• Pregnancy and lactation (to support fetal and infant skeletal development)
• Postmenopausal women at risk of bone loss
• Individuals with malabsorption disorders (e.g., celiac disease, Crohn's disease)
• Pseudohypocalcemia, often seen in low albumin states.
• Acidosis/alkalosis, affecting serum calcium levels.
• Acute pancreatitis, leading to calcium precipitation.
• Severe sepsis/critical illness/trauma, causing impaired calcium regulation.
• Hypomagnesemia/hypermagnesemia, affecting PTH secretion and sensitivity.
• Acute hyperphosphatemia, resulting in calcium phosphate deposition.
• Drugs such as bisphosphonates, denosumab, cinacalcet, cisplatin, and foscarnet.
• Osteoblastic metastasis, causing increased calcium uptake into bones.

What Type of Calcium Supplement Should I Take?

Different forms of calcium are available, and may provide additional benefits above the benefits of calcium.

Calcium carbonate: the most common form, it is cost-effective and contains the highest amount of elemental calcium, often taken with meals due to requiring stomach acid for absorption.

Calcium citrate: well-absorbed regardless of stomach acid levels, suitable for individuals with low stomach acid or on acid-reducing medications, can be taken without food.

Calcium gluconate: contains a lower percentage of elemental calcium, often used intravenously in emergency situations or for rapid correction of calcium levels.

Calcium malate: a less common form of calcium supplement that combines calcium with malic acid, believed to enhance absorption due to the presence of malic acid, which may improve gastrointestinal tolerance and absorption.

Calcium lactate: easily absorbed form of calcium, can be taken with or without food, less commonly used compared to carbonate and citrate.

Calcium phosphate: less commonly used as a supplement due to lower elemental calcium content, may be found in combination with other minerals like magnesium.

Lab Testing Options for Calcium Levels

Testing Information and Sample Type

Calcium testing is a fundamental component of the comprehensive metabolic panel, a routine blood test used to assess overall health and organ function. The procedure involves obtaining a blood sample typically via venipuncture from a vein in the arm. 

Some specialized lab companies offer calcium testing as part of a comprehensive vitamin and mineral assessment panel.

Urine calcium testing may also be done, which is often either ordered as a 24 hour urine collection test or as a spot or random urine assessment.  

Preparation for Lab Test

Prior to the test, it is advisable for individuals to fast for at least 8 hours to ensure accurate results, as eating can affect calcium levels in the blood. Additionally, certain medications such as diuretics or calcium supplements may interfere with the test and should be temporarily discontinued before the blood draw. 

Urine tests require a urine collection.  

Interpreting Test Results

Reference Range for Calcium

While it is recommended to consult with the ordering lab company, typical reference ranges for calcium include:  [7.]

‍< 10 days: 7.6-10.4 mg/dL; 1.9-2.6 mmol/L

Umbilical: 9-11.5 mg/dL; 2.25-2.88 mmol/L

10 days-2 years: 9-10.6 mg/dL; 2.3-2.65 mmol/L

Child: 8.8-10.8 mg/dL; 2.2-2.7 mmol/L

Adult: 9-10.5 mg/dL; 2.25-2.62 mmol/L (Values tend to be reduced in elderly persons.)

Possible critical values for total calcium are < 6 mg/dL or >13 mg/dL.

Clinical Significance of High Calcium Levels  [8.]

Hypercalcemia is characterized by elevated levels of calcium in the blood.  It primarily stems from excess parathyroid hormone (PTH), with causes including adenoma/hyperplasia of the gland, familial hypocalciuric hypercalcemia, and certain endocrine neoplasia syndromes. 

Additionally, malignancies such as renal carcinomas, leukemias, and lymphomas can elevate calcium levels via PTH-related peptides, while hypervitaminosis D, endocrine disorders like thyrotoxicosis, and miscellaneous factors such as renal failure or thiazide diuretic use also contribute. 

Other rare causes encompass genetic syndromes like Williams and Murk Jansen syndromes, hypervitaminosis A, and conditions like milk-alkali syndrome or subcutaneous fat necrosis. 

Hypercalcemia's prevalence in the general population ranges from 1% to 2%, primarily attributed to primary hyperparathyroidism and malignancy-related cases, with the latter representing 90% of hypercalcemia cases overall. 

The regulation of calcium levels involves various factors including PTH, calcitonin, and vitamin D actions, with primary hyperparathyroidism resulting from adenoma or diffuse hyperplasia of the parathyroid gland. 

Conversely, familial hypocalciuric hypercalcemia arises from an inactivating mutation in the calcium-sensing receptor gene, while ectopic vitamin D production from granulomatous lesions can also contribute to hypercalcemia.

Clinical Significance of Low Calcium Levels  [1.]

In contrast to hypercalcemia, hypocalcemia can be caused by PTH deficiency, although other causes are important to consider.

PTH Deficiency:

• Postsurgical loss: Most common after thyroidectomy, parathyroidectomy, or radical neck surgery.
• Autoimmune causes: Leading cause is autoimmune hyperparathyroidism.
• Abnormal parathyroid gland development: Linked with genetic disorders like DiGeorge syndrome.
• Parathyroid gland destruction: Occurs due to infiltrative diseases, chemotherapy, or radiation.

High PTH Levels:

• High PTH may be caused by absolute or relative vitamin D deficiency, which causes a decrease in calcium levels in serum, and a compensatory rise in PTH.
• Chronic kidney disease (CKD): in CKD, vitamin D production and phosphate excretion is decreased.  This causes a compensatory rise in PTH, although increased serum calcium is not seen.  
• Pseudohypoparathyroidism (PHP): a genetic disorder causing resistance to the effects of PTH, which drives further PTH production.  

Other Causes:

• Pseudohypocalcemia.
• Acidosis/alkalosis.
• Acute pancreatitis.
• Severe sepsis/critical illness/trauma.
• Hypomagnesemia/hypermagnesemia.
• Acute hyperphosphatemia.
• Drug-induced hypocalcemia: Bisphosphonates, denosumab, cinacalcet, cisplatin, foscarnet.
• Massive blood transfusion.
• Pregnancy.
• Osteoblastic metastasis.

Natural Ways to Optimize Calcium Levels

Enjoy Dietary Calcium Sources:

• Increase intake of calcium-rich foods such as dairy products (milk, yogurt, cheese), leafy green vegetables (kale, spinach, collard greens), tofu, almonds, and sardines.
• Consume calcium-fortified foods and beverages like fortified orange juice or cereals.
• Incorporate foods rich in vitamin D which aids in calcium absorption, such as fatty fish (salmon, mackerel), egg yolks, and fortified foods like milk or cereal.  [3.] 

Prioritize Healthy Lifestyle Habits:

• Ensure regular weight-bearing exercise, such as walking, jogging, or resistance training, which helps maintain bone density and strength.  [10.]
• Get adequate sunlight exposure to promote natural vitamin D synthesis in the skin.  [3.] 
• Avoid excessive alcohol consumption and smoking, which can impair bone health and calcium absorption.  [9.]
• Maintain a healthy body weight, as being underweight or overweight can negatively impact bone health.  [5.]

Order Testing for Calcium Levels 

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