Calcium
Calcium is the most abundant mineral in the human body, essential for numerous physiological processes. It is a critical component of the skeleton, providing structural integrity to bones and teeth. Beyond its structural role, calcium ions ($text{Ca}^{2+}$) in the circulatory system and tissues are fundamental for blood vessel contraction and dilation, muscle function, nerve transmission, blood clotting, and hormonal secretion [1].
As a dietary supplement, calcium is commonly available in two primary forms: Calcium Carbonate ($text{CaCO}_3$) and Calcium Citrate ($text{Ca}_3(text{C}_6text{H}_5text{O}_7)_2$).
Chemical/Botanical Basics
- Calcium Carbonate is a compound found naturally in rocks, shells, and pearls. It is the most common and least expensive form of calcium supplement. It contains the highest percentage of elemental calcium (approximately 40%) by weight [1, 2]. Due to its reliance on stomach acid for dissolution and absorption, it must be taken with food for optimal absorption [2].
- Calcium Citrate is the calcium salt of citric acid. It contains less elemental calcium (approximately 21%) by weight than the carbonate form [1]. However, it is more soluble and does not require stomach acid for absorption, meaning it can be taken on an empty stomach and is often recommended for individuals with low stomach acid (e.g., older adults or those taking acid-blocking medications) [2, 3].
Mechanism of Action (MoA)
The primary mechanism of action for supplemental calcium is to increase the total body pool of calcium, ensuring adequate levels for all metabolic functions and supporting bone mineralization.
- Absorption: Calcium is absorbed in the small intestine via two main processes:
- Active transport: Saturable, vitamin D-dependent transport that is most efficient at lower calcium intakes.
- Passive diffusion: Non-saturable, paracellular transport that accounts for a larger proportion of absorption at higher intakes [1].
- Homeostasis: The body maintains tight control over serum calcium levels through a complex interplay of parathyroid hormone (PTH), vitamin D (calcitriol), and calcitonin. When dietary intake is insufficient, PTH is released, which stimulates the release of calcium from bone (resorption) to maintain the necessary blood concentration [1].
- Structural Role: The absorbed calcium is incorporated into the bone matrix as calcium hydroxyapatite, a crystal lattice structure, which provides strength and rigidity to the skeleton [1].
2. Chemical Composition/Key Bioactive Roles
The key bioactive role of the supplements is the delivery of elemental calcium ($text{Ca}^{2+}$) for absorption. The difference in the chemical composition of the two forms dictates their bioavailability and usage profile.
| Compound | Chemical Formula | Elemental Calcium (%) | Bioavailability/Usage |
|---|---|---|---|
| Calcium Carbonate | $text{CaCO}_3$ | $approx 40%$ | Requires stomach acid for absorption; best taken with food. |
| Calcium Citrate | $text{Ca}_3(text{C}_6text{H}_5text{O}_7)_2$ | $approx 21%$ | Acid-independent absorption; can be taken on an empty stomach. |
| Elemental Calcium | $text{Ca}^{2+}$ | $100%$ | Essential mineral for bone health, muscle contraction, and nerve function. |
3. Health Benefits
Adequate calcium intake is crucial for preventing deficiency and supporting several health outcomes, with the most robust evidence relating to bone health.
Bone Health and Osteoporosis Prevention
Calcium, often in combination with Vitamin D, is a cornerstone for the prevention and management of osteoporosis and bone fractures.
- Bone Mineral Density (BMD): Numerous studies show that calcium supplementation, particularly in individuals with low dietary intake, helps to slow the rate of bone loss and maintain BMD, especially in the hip and spine [1, 4]. A meta-analysis of randomized controlled trials found that calcium supplementation reduced the rate of bone loss, particularly in the first two years of treatment [5].
- Fracture Risk: While the evidence is mixed, a large body of research suggests that combined calcium and vitamin D supplementation significantly reduces the risk of fractures, particularly in older adults and institutionalized individuals [1, 5]. For example, a study in postmenopausal women with low calcium intake found that supplementation reduced the risk of non-vertebral fractures [6].
Blood Pressure Regulation
Some evidence suggests that calcium intake may play a role in blood pressure regulation, particularly in individuals with low baseline intake.
- Hypertension: A high-quality meta-analysis of randomized controlled trials (RCTs) indicated that calcium supplementation modestly reduced both systolic and diastolic blood pressure in normotensive and hypertensive individuals [1]. The effect is more pronounced in younger people and those with lower baseline calcium intake [1].
Colon Cancer Prevention
Observational and interventional studies have explored a link between calcium intake and a reduced risk of colorectal adenomas (polyps) and cancer.
- Adenoma Recurrence: A large RCT demonstrated that calcium supplementation (1,200 mg/day) significantly reduced the risk of recurrent colorectal adenomas over a 3- to 5-year period [7]. The mechanism is thought to involve calcium binding to bile acids and fatty acids in the gut, reducing their proliferative effects on the colon lining [1].
4. Dosage and Usage
Recommended Intakes (Elemental Calcium)
The Recommended Dietary Allowances (RDAs) for calcium, expressed as elemental calcium, vary by age and sex [1]:
| Age Group | RDA (mg/day) |
|---|---|
| Children (4–8 years) | 1,000 mg |
| Adolescents (9–18 years) | 1,300 mg |
| Adults (19–50 years) | 1,000 mg |
| Adult Males (51–70 years) | 1,000 mg |
| Adult Females (51–70 years) | 1,200 mg |
| Adults (>70 years) | 1,200 mg |
| Pregnant/Lactating | 1,000–1,300 mg |
Supplement Usage
- Calcium Carbonate: Should be taken with food to ensure adequate stomach acid for dissolution and absorption.
- Calcium Citrate: Can be taken with or without food.
- Dosing: To maximize absorption, total daily supplemental calcium should be divided and taken in doses of 500 mg elemental calcium or less at a time [1].
Food Sources (Elemental Calcium)
Dairy products are the most concentrated food sources of calcium.
| Food Source | Serving Size | Elemental Calcium (mg) |
|---|---|---|
| Plain Yogurt (low-fat) | 8 oz | 415 |
| Milk (non-fat) | 8 oz | 300 |
| Cheddar Cheese | 1.5 oz | 307 |
| Fortified Orange Juice | 8 oz | 349 |
| Canned Sardines (with bones) | 3 oz | 325 |
| Kale (cooked) | 1 cup | 94 |
5. Safety and Precautions
The Tolerable Upper Intake Level (UL) for calcium for adults (19–50 years) is 2,500 mg/day and for adults over 51 years is 2,000 mg/day [1]. Intake above the UL, primarily from supplements, can lead to adverse effects.
Side Effects
- Gastrointestinal Distress: The most common side effects are mild, including constipation, gas, and bloating, particularly with Calcium Carbonate [1].
- Kidney Stones: High calcium intake, especially from supplements, is associated with an increased risk of kidney stones in susceptible individuals [1].
Contraindications and Drug Interactions
- Hypercalcemia: Individuals with conditions that cause high calcium levels (e.g., hyperparathyroidism, sarcoidosis) should avoid calcium supplements.
- Drug Interactions: Calcium can interfere with the absorption of several medications. Supplements should be taken at least 2 hours before or 4–6 hours after the following:
- Antibiotics: Quinolones (e.g., ciprofloxacin) and tetracyclines (e.g., doxycycline) [1].
- Thyroid Hormone: Levothyroxine [1].
- Bisphosphonates: Used for osteoporosis (e.g., alendronate) [1].
- Proton Pump Inhibitors (PPIs) and $text{H}_2$ Blockers: These acid-reducing medications decrease stomach acid, which can impair the absorption of Calcium Carbonate but not Calcium Citrate [2].
Serious Safety Warnings
- Cardiovascular Risk: Some large observational studies have suggested a potential link between high-dose calcium supplementation (without co-administered vitamin D) and an increased risk of cardiovascular events, such as myocardial infarction [8]. However, other large-scale RCTs have not confirmed this risk, and the evidence remains conflicting [1]. It is generally recommended to obtain calcium primarily through diet and to use supplements only to bridge a documented gap.
- Milk-Alkali Syndrome: Excessive intake of calcium (often from supplements) combined with absorbable alkali (e.g., antacids) can lead to this serious condition, characterized by hypercalcemia, metabolic alkalosis, and renal failure [1].
6. References
[1] National Institutes of Health, Office of Dietary Supplements. Calcium: Health Professional Fact Sheet. Available at: https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/[2] GoodRx. Calcium Citrate vs. Calcium Carbonate: Which Supplement Is Best? Available at: https://www.goodrx.com/calcium-carbonate/calcium-carbonate-vs-calcium-citrate[3] Sakhaee, K., et al. (1999). A comparison of calcium citrate with calcium carbonate in the absorption of calcium in postmenopausal women. The American Journal of Therapeutics, 6(3), 169-174. Available at: https://pubmed.ncbi.nlm.nih.gov/11329115/[4] Tang, B. M. P., et al. (2007). Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. The Lancet, 370(9588), 657-666. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61342-7/fulltext[5] Weaver, C. M., et al. (2016). Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporosis International, 27(1), 367-376. Available at: https://link.springer.com/article/10.1007/s00198-015-3386-w[6] Reid, I. R., et al. (2015). Calcium supplementation and risk of fracture in women and men: a meta-analysis of randomised controlled trials. The Lancet, 385(9976), 1517-1526. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62234-5/fulltext[7] Baron, J. A., et al. (1999). Calcium supplements for the prevention of colorectal adenomas. New England Journal of Medicine, 340(2), 101-107. Available at: https://www.nejm.org/doi/full/10.1056/NEJM199901143400202[8] Bolland, M. J., et al. (2011). Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ, 342, d2040. Available at: https://www.bmj.com/content/342/bmj.d2040Category: Mineral
