Tools
Dietary Calcium and Supplementation
Indications
The Institute of Medicine of the National Academies established the recommendations for dietary calcium intake, with the most recent guidelines released in 2010. These recommendations were based on high-quality research studies and data gathered over the preceding decade. In summary, the Institute of Medicine committee reviewed current literature on health outcomes of calcium and vitamin D intake. They concluded that although these nutrients are crucial for maintaining bone health, their role in other health conditions is less definitive. This committee released dietary reference intake values, such as recommended dietary allowance (RDA) and estimated average requirement measurements, to serve as a guideline for appropriate calcium and vitamin D intake in healthy individuals across different age groups.[1]
The RDA values from the CDC factsheet are summarized below [CDC. Recommended Dietary Allowance of Calcium].
| Age | Female | Male | Pregnancy | Lactation |
| 0–6 months* | 200 mg | 200 mg | ||
| 7–12 months* | 260 mg | 260 mg | ||
| 1–3 years | 700 mg | 700 mg | ||
| 4–8 years | 1000 mg | 1000 mg | ||
| 9–13 years | 1300 mg | 1300 mg | ||
| 14–18 years | 1300 mg | 1300 mg | 1300 mg | 1300 mg |
| 19–50 years | 1000 mg | 1000 mg | 1000 mg | 1000 mg |
| 51–70 years | 1200 mg | 1000 mg | ||
| >70+ years | 1200 mg | 1200 mg |
The Food and Drug Administration (FDA) acknowledges that inadequate calcium and vitamin D intake can contribute to low peak bone mass, an identifiable risk factor for osteoporosis. The official FDA statement emphasizes that adequate calcium and vitamin D are crucial components of a healthy diet, and regular physical activity can help reduce the risk of osteoporosis later in life. However, no specific discussion is available on calcium supplementation. The FDA does provide daily values on food products to educate consumers on the calcium content within the context of a recommended diet. The most recent daily value for calcium is 1300 mg for adults and children older than 4. Sufficient calcium intake is achievable from a well-balanced diet.
Calcium supplementation is indicated when dietary calcium intake is insufficient, as determined by a patient's dietary history. Generally, obtaining calcium through a well-balanced diet is preferred to supplementation. Potential indications for calcium supplementation include osteoporosis, osteomalacia, hypocalcemic rickets, hypoparathyroidism, and hypocalcemia from chronic kidney disease. The most common indication for calcium supplementation is to prevent or slow the progression of osteoporosis. Several randomized prospective clinical trials have demonstrated that daily calcium and vitamin D supplementation improves bone density in postmenopausal women and older men.[2][3][4][5] However, different trials have yielded conflicting results regarding the impact of supplementation on reducing the risk of pathological fractures. Differences in patient populations and demographics, such as living arrangements (community versus assisted living), may account for these varying outcomes. One of the largest and most-cited trials, the Women's Health Initiative, found that calcium and vitamin D supplementation in healthy postmenopausal women led to a small but significant improvement in hip bone density. However, it did not significantly reduce the incidence of hip fractures.[6][7][8][9][10]
According to the American College of Cardiology (ACC), patients typically take calcium supplementation for bone health rather than cardiovascular health. Daily doses of 1000 to 1200 mg of calcium combined with vitamin D have shown modest benefits in reducing fractures. Exceeding the recommended amounts has not demonstrated additional benefits. Aiming to achieve the RDA of calcium through dietary sources and considering supplemental calcium only for individuals consuming less than 800 mg/d are recommended, especially for individuals who cannot increase their calcium intake from food.[11]
Mechanism of Action
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Mechanism of Action
Calcium is absorbed through 2 main mechanisms:
- A transcellular active transport process in the duodenum and jejunum
- A paracellular passive transport process along the entire small intestine
Calcium level regulation occurs through several signaling molecules, including parathyroid hormone, vitamin D, and calcitonin. Calcium is critical for many physiological functions. Calcium is a major component of the bone matrix and teeth. In addition, various calcium channels are involved in blood vessel constriction and relaxation, muscle contraction, nerve action potentials, and cardiac electrophysiology. Calcium ions are also an important component of blood clotting pathways.[12][13][14][15]
Administration
A balanced diet can provide sufficient calcium intake. A wide array of natural calcium sources exist, including dairy products, such as milk, yogurt, and cheese; vegetables, such as broccoli and kale; and foods fortified with calcium, such as fruit juices, cereals, and some grains.
Available Dosage Forms and Strengths
The 2 primary oral forms of supplemental are calcium carbonate and calcium citrate. Calcium carbonate is cheaper and more commonly used. The absorption and bioavailabilities of these 2 compounds differ significantly. Calcium carbonate depends on the stomach's acidic environment for adequate absorption and should be taken with food; calcium citrate has no such requirement.[16] Results of several studies have shown that calcium citrate has a significantly higher bioavailability compared to calcium carbonate.[17] This increased absorbability is advantageous in situations that adversely affect calcium absorption through reduced stomach acid production, such as a patient with a Roux-en-Y bypass. Notably, the absorption kinetics of orally administered calcium depends on the absolute amount of calcium. As the dose of calcium increases, the percentage absorbed decreases.[18] According to the American Association of Clinical Endocrinology (AACE), patients with achlorhydria, a history of gastric surgery, or receiving proton-pump inhibitors or H2-receptor blockers should be prescribed calcium citrate over calcium carbonate. To maximize absorption, calcium supplements should not exceed 500 mg of elemental calcium per dose, as absorption efficiency declines with higher amounts.[19] Other oral forms of calcium, although less widely used, include calcium phosphate, lactate, and gluconate.[20]
Intravenous (IV) formulations of calcium are available and are used to rapidly correct low serum calcium to prevent seizure, tetany, or cardiac arrhythmias.[21] IV calcium gluconate is commonly used to correct acute hypocalcemia (corrected calcium greater than 7 mg/dL), occasionally observed as a complication after head and neck surgery when native parathyroid glands are disturbed.[22] IV calcium gluconate is also administered to patients with prolonged QT intervals to prevent cardiac arrhythmias.[23] Dosing IV calcium requires care to prevent cardiac dysfunction and potential cardiac arrest.[24]
Adult Dosage
The RDA for calcium has been discussed in the Indications section above.
Specific Patient Populations
Renal impairment: When considering calcium supplementation, renal function is important. Studies reveal that the majority of patients with chronic kidney disease do not have symptomatic hypocalcemia, although certain medications such as bisphosphonates and denosumab may increase this risk. Patients with severe chronic kidney disease should maintain adequate serum calcium levels. In adult patients with chronic kidney disease, stages G3a to G5D, avoiding hypercalcemia is recommended. For children with chronic kidney disease stages G3a to G5D, maintaining serum calcium within the age-appropriate normal range is advised according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.[25][26][27][28]
Hepatic impairment: According to the European Association for the Study of the Liver (EASL), patients with chronic liver disease should maintain a balanced diet due to frequent malnutrition. EASL recommends calcium supplements (1000–1500 mg/d) and vitamin D supplements (400–800 IU/d or 260 mcg every 2 weeks) to preserve normal levels, especially in patients with a T-score below −1.5. However, the effectiveness in preventing bone loss remains uncertain. According to the American Association for the Study of Liver Diseases (AASLD), liver transplant recipients with osteopenia should engage in regular weight-bearing exercise and receive calcium and vitamin D supplements.[29][30]
Breastfeeding considerations: Women younger than 19 should consume 1300 mg of calcium daily during pregnancy and lactation. For women older than 19, the RDA of 1000 mg of calcium aligns with the general population's RDA.[31]
Pregnancy considerations: The American College of Obstetricians and Gynecologists (ACOG) notes that calcium may reduce the severity of preeclampsia with low calcium intake. However, this benefit does not apply to populations in the United States with adequate calcium intake per the RDA.[32]
Postmenopausal patients: ACOG guidelines for preventing osteoporosis in postmenopausal women recommend counseling patients on the importance of calcium and vitamin D for bone health. A total of 1200 mg of calcium per day (including supplements) is suggested.[33]
Pediatric patients: According to the 2013 guidelines of the American Academy of Pediatrics (AAP), preterm infants weighing less than 1800 to 2000 g should be given diets high in minerals to prevent rickets. The diets should include specialized formulas for preterm infants or fortifying human milk.[34]
Older patients: The American Geriatrics Society (AGS) strongly recommends that clinicians advise adults aged 65 and older to take daily vitamin D 1000 IU and calcium supplements to lower the risk of fractures and falls.[35]
Adverse Effects
Excessive intake of calcium can result in adverse effects. The Institute of Medicine of the National Academies has stated that a daily calcium intake of 2000 mg or more increases the risk of adverse effects.[18] The adverse effects of calcium supplements are mainly gastrointestinal, including constipation, dyspepsia, nausea, and vomiting. The risk and severity of these adverse effects are improved by taking calcium supplements with food. Another adverse effect is an increased risk of nephrolithiasis. Notably, high dietary calcium intake has not correlated with an increased incidence of kidney stones. However, oral calcium supplements have been shown to increase this risk. The cause of this paradoxical effect is still a topic of debate.
Another interesting point regarding high calcium consumption is its role in regulating energy metabolism; high-calcium diets mitigate adipocyte lipid accumulation and weight gain during periods of overconsumption of an energy-dense diet, increasing lipolysis and preserving thermogenesis during caloric restriction, accelerating weight loss. Intracellular Ca2+ plays a vital role in regulating triglyceride storage and adipocyte lipid metabolism; increased intracellular Ca2+ stimulates lipogenic gene expression, lipogenesis, suppression of lipolysis, and increased adiposity. These findings support clinical and epidemiological data demonstrating a reduction in the odds of obesity that correlates with increased dietary calcium intake. Notably, dairy sources of calcium demonstrate an increased anti-obesity effect compared to supplemental calcium sources in the studies examining this phenomenon. However, excessive calcium consumption can lead to the gastrointestinal effects described earlier.
Although controversial, another potential adverse event of excessive calcium intake is the worsening of underlying cardiovascular disease. Two separate meta-analyses demonstrated a potential marginal increased risk of myocardial infarction in patients receiving calcium supplementation versus controls. However, other studies and meta-analyses have shown no association between calcium supplementation and the risk of myocardial infarction. The National Osteoporosis Foundation has stated that substantial evidence supports that taking the recommended amount of calcium supplements poses no risk to the heart.
According to the CDC, hypercalcemia (serum levels >10.5 mg/dL [2.63 mmol/L]) and hypercalciuria (>250 mg/d in women, >275 mg/d in men) are rare in healthy individuals, typically associated with conditions such as cancer and hyperparathyroidism. Symptoms may include muscle weakness, renal insufficiency, constipation, nausea, fatigue, and an increased risk of cardiovascular mortality. High calcium intake may also elevate risks of cardiovascular disease and prostate cancer, although findings across studies are inconsistent.[36]
Drug-Drug Interactions
- Due to chelation, blood levels of dolutegravir are reduced with calcium supplements. The doses should be separated by at least 2 hours before or 6 hours after calcium intake.
- Calcium carbonate supplements can interfere with the absorption of levothyroxine. Patients are advised to take these medications at least 4 hours apart.
- Long-term use of lithium may lead to hypercalcemia, and combining the medication with calcium supplements could increase the risk.
- Quinolone antibiotics, such as ciprofloxacin and moxifloxacin, have reduced absorption when taken simultaneously with calcium supplements. To prevent interactions, these antibiotics are recommended 2 hours before or after calcium supplements.
Contraindications
Although no absolute contraindications are stated for calcium supplementation, some conditions should be considered. These conditions include patients with renal impairment or chronic kidney disease and a history of calcium-containing kidney stones. The literature regarding the risks and benefits of calcium supplementation in patients with chronic kidney disease is not robust, and further research is necessary to optimize calcium supplementation in this sub-population. Studies indicate that patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 may be at an increased risk of certain adverse effects of calcium supplementation. Calcium supplementation of over 2000 mg daily can suppress parathyroid secretion in patients with advanced chronic kidney disease. Other studies have raised the concern that patients taking calcium and phosphorus binders with severe chronic kidney disease may have an increased risk of vascular calcification and atherosclerosis. Avoiding excessive calcium intake in patients with moderate-to-severe chronic kidney disease and monitoring these levels is important.[37]
Patients with a known risk or history of calcium-containing nephrolithiasis should avoid excessive calcium intake in supplements. Notably, the risk of calcium-containing stones increases with oral calcium supplementation but is reducible with dietary calcium. The mechanism of these paradoxical effects is debated. The effects are related to the dietary sources of calcium, which can contain oxalate, bind to calcium, and limit overall absorption. In addition, a major clinical trial (Women's Health Initiative) found that postmenopausal women who received calcium and vitamin D supplements had an increased incidence of kidney stones relative to a placebo group.[38][39][40][41][42]
Monitoring
The established upper limit of calcium intake is 2500 mg for adults aged 19 to 50 and 2000 mg for adults aged 51 and older. A recent study summarizing trends in calcium intake based on the National Health and Nutrition Examination Survey found that mean supplemental calcium intake reached a maximum from 2007 to 2008 and subsequently decreased. In 2013 and 2014, it was estimated that 0.4% of the population had exceeded the tolerable upper intake level (UL) for daily calcium intake. Supplemental calcium intake was higher among women, non-Hispanic whites, and adults older than 60.[18][43]
Generally, calcium is not subject to routine monitoring in otherwise healthy patients. On a related note, the United States Preventative Service Task Force (USPSTF) states that current evidence, such as grade I, regarding the advantages and disadvantages of vitamin D screening in asymptomatic adults is insufficient. However, calcium levels are regularly monitored in patients with several other conditions, including renal insufficiency; chronic kidney disease; recurrent nephrolithiasis; hyperparathyroidism; hypoparathyroidism; gastrointestinal disorders, such as celiac disease; and vitamin D deficiency. The dietary and supplemental calcium intake is adjusted based on frequent patient monitoring. Calcium correction for hypoalbuminemia should be taken into consideration.
Corrected calcium (mg/dL) = reported total calcium (mg/dL) + 0.8 (4.0 – serum albumin (g/dL)). Studies have shown that patients with cardiac arrest and either low or high albumin-corrected calcium levels (<8.86 or >10.32) have increased all-cause mortality risks, underscoring the importance of albumin-corrected calcium monitoring in clinical management.[44] According to the AACE, patients diagnosed with osteoporosis or at risk of bone loss should undergo 24-hour urine calcium collection. This test helps evaluate calcium sufficiency and screens for conditions such as hypercalciuria or malabsorption.[19]
Toxicity
According to the CDC, hypercalcemia (serum levels >10.5 mg/dL [2.63 mmol/L]) and hypercalciuria (>250 mg/d in women, >275 mg/d in men) are rare in healthy individuals, typically associated with conditions such as cancer and hyperparathyroidism. Symptoms may include muscle weakness, renal insufficiency, constipation, nausea, fatigue, and an increased risk of cardiovascular mortality. High calcium intake may also elevate the risk of cardiovascular disease and prostate cancer, although findings across studies are inconsistent.
Signs and Symptoms of Overdose
Hypercalcaemia may present with polyuria, anorexia, nausea, constipation, mood disturbances, cognitive dysfunction, coma, shortened QT interval, dysrhythmias, nephrolithiasis, pancreatitis, peptic ulceration, hypertension, cardiomyopathy, muscle weakness, and band keratopathy.
Management of Overdose
There is no specific antidote or treatment available for excessive supplemental calcium intake. Initial management involves rehydration with IV 0.9% saline at 4 to 6 L/d, with careful monitoring for fluid overload in patients with renal impairment or of older age. Loop diuretics should be used cautiously and only if fluid overload is evident, as they are ineffective for lowering serum calcium levels. Dialysis may be considered for severe renal failure. Further treatment options include IV bisphosphonates, such as zoledronic acid, pamidronate, and ibandronic acid, administered cautiously with dose adjustments in renal impairment. Glucocorticoids, such as prednisolone, inhibit 1,25-dihydroxyvitamin D production, particularly effective in lymphoma or granulomatous diseases. If initial therapies are ineffective, calcimimetics, denosumab, or calcitonin are recommended under specialist supervision. Parathyroidectomy may be considered for acute severe hypercalcemia due to primary hyperparathyroidism resistant to other treatments.[45]
According to the Endocrine Society guidelines for hypercalcemia of malignancy, treatment options vary based on specific conditions. Treatment includes IV bisphosphonate or denosumab as primary management options. For severe hypercalcemia of malignancy (Ca2+ >14 mg/dL), calcitonin may be added initially. Denosumab is preferred in refractory or recurrent cases. For tumors with high calcitriol levels, IV bisphosphonate or denosumab is recommended. Treatment options for hypercalcemia from parathyroid carcinoma include calcimimetic, IV bisphosphonate, or denosumab.[46]
Enhancing Healthcare Team Outcomes
Ensuring that individual patients and the larger population understand bone health and the benefits of proper calcium intake and nutrition requires interprofessional collaboration. At the clinical level, clinicians must collaborate to accurately identify patients with varying risks of poor bone health and to focus on high-risk patients. Clinicians must also collaborate to ensure that healthy and young patients receive education on the importance of adequate calcium intake and long-term health benefits. Interprofessional collaboration also allows clinicians to educate one another, ensuring adherence to the best evidence-based practice guidelines.
A recent randomized prospective trial assessed the efficacy of an interprofessional educational intervention to improve the management of osteoporosis.[47] Specifically, several long-term care homes participated in 3 educational meetings over 1 year, emphasizing quality improvement, expert opinions, and clinician audit and feedback. A control group of facilities that received no such intervention served as a comparison. This trial demonstrated a significant increase in the prescription of vitamin D and calcium in the intervention group versus the control group. A recent cohort study assessed the efficacy of a drug use evaluation program in improving the management of osteoporosis.[48] Pharmacists led the program and were involved in group education conferences, prescriber feedback, and patient education. The program yielded a statistically significant increase in vitamin D and calcium supplementation in patients when supplementation was indicated. Similar studies demonstrate the importance of continuing education and interprofessional teamwork to ensure patients receive appropriate bone health care and nutrition.
At the public health level, interprofessional collaboration is essential for promoting population health and nutrition. A prime example is the continuing effort to fortify various fruit juices and grains with calcium and vitamin D, targeting young patients who have not reached peak bone mass. Today, various national organizations collaborate across professions to advance bone health and nutrition at the population level, including the National Osteoporosis Foundation, the National Academy of Sciences, and the National Bone Health Alliance. The interprofessional team comprises clinicians, pharmacists, nursing staff, and dieticians. These professionals should share their expertise among team members, monitor patient compliance, answer questions, and work collaboratively to guide patient outcomes. An interprofessional team approach and communication among clinicians, pharmacists, and nurses are crucial for decreasing potential adverse effects and improving patient outcomes associated with dietary or supplemental calcium.[49][50]
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