Continuing Education Activity

Adequate calcium intake, from either direct food sources or calcium supplements, is essential for nutrition in patients of all ages. This article will summarize dietary sources of calcium, the current recommendations for calcium intake, the different types of calcium supplementation, the preventative measures and health benefits of calcium, and the potential risks of excessive calcium intake. Additionally, this article will highlight the role of interprofessional team members in ensuring that patients receive appropriate dietary calcium for growth, nutrition, and disease prevention.

Objectives:

• Describe the current recommendations regarding healthy calcium intake based on the indications for and the different formulations of calcium supplementation.
• Outline the critical steps involved in calcium absorption, metabolism, and regulation, and summarize the main physiologic functions dependent upon ionized calcium.
• Review any potential adverse events associated with excessive calcium intake, including special considerations regarding calcium intake in specific high-risk populations like those with chronic kidney disease.
• Summarize interprofessional team strategies for improving care coordination and communication regarding adequate calcium supplementation to improve bone health and nutrition in both general and high-risk populations.

Indications

The recommendations for dietary calcium intake are established by the Institute of Medicine of the National Academies. They released the most current recommendations in 2010 and based on high-quality research studies and information from the decade prior.[1] In summary, the Institute of Medicine committee reviewed current literature pertaining to health outcomes of calcium and vitamin D intake. The determination was that these nutrients most certainly play an essential role in bone health, but not necessarily in other health conditions. This committee released dietary reference intake (DRI) values, such as recommended dietary allowance (RDA) and estimated average requirement (EAR) measurements to serve as a guideline for appropriate calcium and vitamin D intake in healthy patients of different age groups.[1] The recommended daily allowance (RDA) values are summarized below.

• 1 to 3 years old: 700 mg/daily
• 4 to 8 years old: 1,000 mg/daily
• 9 to 13 years old: 1,300 mg/daily
• 14 to 18 years old: 1,300 mg/daily
• 19 to 30 years old: 1,000 mg/daily
• 31 to 50 years old: 1,000 mg/daily
• 51 to 70-year-old males: 1,000 mg/daily
• 51 to 70-year-old females: 1,200 mg/daily
• Over 70 years old: 1200 mg/daily
• 14 to 18 years old females (pregnant/lactating): 1,300 mg/daily
• 19 to 50 years old females (pregnant/lactating): 1,000 mg/daily

The FDA acknowledges that an inadequate intake of calcium and/or vitamin D can contribute to low peak bone mass, which is an identifiable risk factor of osteoporosis. The official FDA statement is that "adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life." However, there is no specific discussion regarding calcium supplementation. The FDA does provide daily values (DV) 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 1,300 mg for adults and children older than four years of age. Sufficient calcium intake is achievable from a well-balanced diet, but many patients do not eat a well-balanced diet.

Calcium supplementation is indicated when dietary calcium intake may be insufficient; the clinician can determine this by a patient's dietary history.  In general, obtaining calcium through a well-balanced diet is preferred to supplementation with other products. Other potential indications for calcium supplementation include osteoporosis, osteomalacia, hypocalcemic rickets, hypoparathyroidism, and hypocalcemia from chronic kidney disease (CKD).

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 whether or not calcium and vitamin D supplementation decrease the risk of pathologic fractures.[6][7][8][9] The suggestion is that differences in patient populations and demographics, specifically in living arrangements (community versus assisted-living), may have led to conflicting results. One of the largest and most-cited trials, the Women's Health Initiative), determined that calcium and vitamin D supplementation in healthy postmenopausal women led to a small but significant improvement in hip bone density but no significant decrease in hip fracture.[10] 

It is important to consider a patient's renal function when considering calcium supplementation. Studies reveal that the majority of patients with CKD will not have symptomatic hypocalcemia, although certain medications like bisphosphonates and denosumab may increase this risk.[11][12][13] In patients with severe CKD, care should be given to ensure adequate serum calcium levels are maintained.

Mechanism of Action

Calcium gets absorbed through two main mechanisms:

1. A transcellular active transport process in the duodenum and jejunum[14]
2. A paracellular passive transport process along the entire small intestine[15]

Calcium level regulation occurs via several signaling molecules, including parathyroid hormone (PTH), vitamin D, and calcitonin. Calcium is critical for many physiologic functions. Calcium is a major component of the bone matrix and teeth. Additionally, 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. 

Administration

Sufficient calcium intake is achievable from a well-balanced diet. A wide array of natural calcium sources exist, including dairy products (e.g., milk, yogurt, cheese), vegetables (e.g., broccoli, kale), and foods fortified with calcium (e.g., fruit juices, cereals, and some grains). 

The two primary oral forms of supplemental are calcium carbonate and calcium citrate.[16] Calcium carbonate is cheaper and more commonly used. The absorption and bioavailabilities of these two compounds differ significantly. Calcium carbonate is dependent on the acidic environment of the stomach for adequate absorption and should be taken with food; however, calcium citrate has no such requirement.[17] Studies have shown that calcium citrate has a significantly higher bioavailability than calcium carbonate.[18] This increased absorbability can be an advantage in situations that adversely affect calcium absorption through reduced stomach acid production, such as a patient with a Roux-en-Y bypass, as one example. Of note, the absorption kinetics of orally administered calcium depends upon the absolute amount of calcium taken. As the dose of calcium increases, the percentage absorbed decreases.[19] Other oral forms of calcium, although less widely used, include calcium phosphate, calcium lactate, and calcium gluconate.[16]

Intravenous formulations of calcium exist and are used to rapidly correct low serum calcium as a means to prevent seizure, tetany, or cardiac arrhythmias.[20] IV calcium gluconate is used to correct acute hypocalcemia (corrected calcium greater than 7 mg/dL), occasionally seen as a complication after head and neck surgery when native parathyroid glands are disturbed.[21] IV calcium gluconate is also given to patients with prolonged QT intervals to prevent cardiac arrhythmias.[22] Dosing IV calcium requires care to prevent cardiac dysfunction and potential cardiac arrest.[23] 

Adverse Effects

Excessive intake of calcium can result in harmful side effects. The Institute of Medicine of the National Academies has stated that calcium intake of 2000 milligrams or more daily increases the risk of harm and adverse events.[19] The most common side effects of calcium supplements include gastrointestinal effects (e.g., constipation, dyspepsia, nausea, vomiting). The risk and severity of these side effects are improvable by taking calcium supplements with food. Another adverse event is an increased risk of nephrolithiasis in individual patients. Of note, 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 pivotal role in the regulation of 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; this situation can accelerate weight loss. Intracellular Ca2+ plays a vital role in the regulation of triglyceride storage and adipocyte lipid metabolism; increased intracellular Ca2+ results in the stimulation of lipogenic gene expression, lipogenesis, suppression of lipolysis, and increased lipid filling and adiposity. These findings have received support from clinical and epidemiological data demonstrating a reduction in the odds of obesity that correlates with increased dietary calcium intake. Of note, dairy sources of calcium demonstrate an increased anti-obesity effect than supplemental calcium sources in the studies that have examined this phenomenon.[24] However, excessively high calcium consumption can lead to the gastrointestinal effects described in the previous paragraph.

Another potential adverse event of excessive calcium intake, although controversial, 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 yielded results that showed no association between calcium supplementation and risk of myocardial infarction. Currently, the National Osteoporosis Foundation has stated that "substantial evidence supports that taking the recommended amount of calcium supplements poses no risk to the heart." 

Contraindications

Although there are no absolute contraindications to calcium supplementation, some conditions should merit special consideration regarding calcium supplementation. These conditions include patients with renal impairment or chronic kidney disease (CKD) and history of calcium-containing kidney stones.

The literature regarding the risks and benefits of calcium supplementation in patients with CKD is not robust, and more research is necessary to optimize calcium supplementation in this sub-population. Studies have shown that patients with an eGFR less than 30 mL/minute/1.73m^2 may be at an increased risk of certain side effects of calcium supplementation. Firstly, research has shown that calcium supplementation between over 2000 mg per day can suppress PTH secretion in patients with advanced CKD.[25] Other studies have raised the concern that patients taking calcium and/or phosphorus binders with severe CKD may have an increased risk of vascular calcification and atherosclerosis.[26][27] Therefore, it is prudent to avoid excessive calcium intake in patients with moderate to severe CKD and regularly monitor these levels. 

In patients with a known risk or history of calcium-containing nephrolithiasis should avoid excessive calcium intake in the form of supplements. Of note, the risk of calcium-containing stones increases with oral calcium supplementation but is reducible with dietary calcium.[28][29] The mechanism of these paradoxical effects is still debated but may be related to the fact that dietary sources of calcium can contain oxalate, which binds to calcium and limits overall absorption. Additionally, a major clinical trial (Women's Health Initiative) determined that postmenopausal women who received calcium and vitamin D supplements had an increased incidence of kidney stones relative to a placebo group.[30]

Monitoring

The established upper limit of calcium intake is 2500 mg for adults aged 19 to 50 years and 2000 mg for adults aged 51 years and older.[19] A recent study summarizing trends in calcium intake based on the National Health and Nutrition Examination Survey determined that mean supplemental calcium intake reached a maximum in 2007 through 2008 and subsequently decreased.[31] In 2013 and 2014, estimates were that 0.4% of the population had taken daily calcium at an amount higher than the tolerable upper intake level (UL). Supplemental calcium intake was greater among women, non-Hispanic whites, and adults older than 60 years of age.[31] 

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 is insufficient (e.g., grade I) regarding the advantages and disadvantages of vitamin D screening in asymptomatic adults. However, calcium levels are regularly monitored in patients with several other conditions, such as renal insufficiency, chronic kidney disease, recurrent nephrolithiasis, hyperparathyroidism, hypoparathyroidism, certain gastrointestinal disorders (e.g., celiac disease), and vitamin D deficiency, among others. The dietary and supplemental calcium intake is adjusted accordingly based on regular monitoring for these patients. 

Toxicity

There is no specific antidote or treatment for excessive intake of supplemental calcium. 

Enhancing Healthcare Team Outcomes

Ensuring that individual patients and the entire population understand bone health and the benefits of proper calcium intake and nutrition requires interprofessional collaboration. At the clinical level, providers must collaborate to accurately identify patients with varying risks of poor bone health and emphasize high-risk patients. Clinicians must also collaborate to ensure healthy and young patients receive education on the importance and long-term health benefits of adequate calcium intake. Interprofessional collaboration also allows clinicians and other providers to educate one another, ensuring adherence to the best evidence-based practice guidelines.

A recent randomized prospective trial (level I evidence) assessed the efficacy of an interprofessional educational intervention to improve osteoporosis management.[32] Specifically, several long-term care homes participated in three educational meetings over one year, emphasizing quality improvement, expert opinions, and provider 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 proper prescribing of vitamin D and calcium in the intervention group versus the control group. A recent cohort study (level III evidence) assessed the efficacy of a drug use evaluation (DUE) program in improving the management of osteoporosis.[33] Pharmacists led the program and involved group education conferences, prescriber feedback, and patient education. The program yielded a statistically significant increase in vitamin D and/or calcium supplementation in patients for which supplementation was indicated. Studies like these demonstrate the importance of continuing education and interprofessional teamwork to ensure that patients receive appropriate bone health care and nutrition. 

At the public health level, interprofessional collaboration is essential for promoting population health and nutrition. One such example is the continuing effort to fortify various fruit juices and grains with calcium and vitamin D, thereby targeting young patients who have not reached peak bone mass.[34][35] Today, several national groups work interprofessionally to promote bone health and nutrition at the population, National Osteoporosis Foundation, National Academy of Sciences, and the National Bone Health Alliance, to name a few. Examples of providers who will make up the interprofessional team include clinicians (diagnosing), pharmacists (verifying dosing and drug/supplementation regimens), nursing staff (counseling and verifying compliance, coordinating care between disciplines), dieticians, and nutritionists (helping the patient make proper dietary and nutrition choices). These disciplines need to share their expertise among team members and with the patient, monitor patient compliance, answer patient questions, and work collaboratively to guide patient outcomes to an optimal result regarding dietary calcium and bone health without causing potential adverse effects. [Level 5]