Search databaseBooksAll DatabasesAssemblyBiocollectionsBioProjectBioSampleBioSystemsBooksClinVarConserved DomainsdbGaPdbVarGeneGenomeGEO DataSetsGEO ProfilesGTRHomoloGeneIdentical Protein Web CatalogNucleotideOMIMPMCPopSetProteinProtein ClustersProtein Family ModelsPubChem BioAssayPubChem CompoundPubChem SubstancePubMedSNPSRAStructureTaxonomyToolKitToolKitAllToolKitBookgh Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

You are watching: Hypocalcemia could be caused by the ______

Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.


Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors.


Calcium as a nutrient is most commonly associated with the formation and metabolism of bone. Over 99 percent of total body calcium is found as calcium hydroxyapatite (Ca1062) in bones and teeth, where it provides hard tissue with its strength. Calcium in the circulatory system, extracellular fluid, muscle, and other tissues is critical for mediating vascular contraction and vasodilatation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion. Bone tissue serves as a reservoir for and source of calcium for these critical metabolic needs through the process of bone remodeling.

Calcium metabolism is regulated in large part by the parathyroid hormone (PTH)–vitamin D endocrine system, which is characterized by a series of homeostatic feedback loops. The rapid release of mineral from the bone is essential to maintain adequate levels of ionized calcium in serum. During vitamin D deficiency states, bone metabolism is significantly affected as a result of reduced active calcium absorption. This leads to increased PTH secretion as the calcium sensing receptor in the parathyroid gland senses changes in circulating ionic calcium. Increased PTH levels induce enzyme activity (1α-hydroxylase) in the kidney, which converts vitamin D to its active hormonal form, calcitriol. In turn, calcitriol stimulates enhanced calcium absorption from the gut. Not surprisingly, the interplay between the dynamics of calcium and vitamin D often complicates the interpretation of data relative to calcium requirements, deficiency states, and excess intake.


Ingested calcium comes from food sources and dietary supplements. In this report dietary calcium refers to both food sources and supplements combined (although some researchers reserve the term dietary calcium to mean only food sources) and is most often referred to as total calcium intake for clarity. With more than one-half of the U.S. population (Bailey et al., 2010)—and between 24 and 60 percent of Canadians (2004 Canadian Community Health Survey, personal communication, D. Brulé, Health Canada, April 29, 2010)—reporting use of dietary supplements of some type, dietary supplements must be taken into account when considering the sources of calcium in the diet and, in turn, estimating total calcium intake. Current estimates from 2003 to 2006 indicate that the median total intake of calcium from all sources for persons > 1 year of age ranges from 918 to 1,296 mg/day, depending upon life stage (Bailey et al., 2010). Only small amounts of calcium are contributed by water, depending upon geographic location. Chapter 7 of this report contains an assessment of quantitative calcium intake in the U.S. and Canadian populations.


Calcium is classically associated with dairy products; milk, yogurt, and cheese are rich sources of calcium, providing the major share of calcium from foods in the general diet in the United States and Canada. In the United States, an estimated 72 percent of calcium comes from milk, cheese and yogurt and from foods to which dairy products have been added (e.g., pizza, lasagna, dairy desserts). The remaining calcium comes from vegetables (7 percent); grains (5 percent); legumes (4 percent); fruit (3 percent); meat, poultry, and fish (3 percent); eggs (2 percent); and miscellaneous foods (3 percent).1 Similar data from Canada are not currently available.

Fortification with calcium for a number of foods that do not naturally contribute calcium—such as orange juice, other beverages, and ready-to-eat cereals—is becoming commonplace in the United States (Calvo et al., 2004; Rafferty et al., 2007; Poliquin et al., 2009). These practices challenge the ability of national food composition databases, such as those maintained by U.S. Department of Agriculture (USDA), to keep abreast of these newer products and may result in some underestimation of actual calcium intake from food sources. However, for those persons who choose such foods, total calcium intake is increased.

Dietary Supplements

Among the U.S. population, about 43 percent of all persons—but almost 70 percent of older women—reported calcium intake from supplements, based on a national survey conducted between 2003 and 2006 (Bailey et al., 2010). When calcium from supplement use is taken into account based on these survey data, the average intake increases by about 7 percent for males and 14 percent for females. However, this is not a meaningful snapshot of the effect of supplement use, because non-users of supplements are averaged with users, meaning that the effect is much more skewed than can be reflected by a mean estimate. Similar data are not available for Canada, but the frequency of use data show that 48 to 82 percent of Canadians reported taking a calcium supplement within the previous 30 days (2004 Canadian Community Health Survey, personal communication, D. Brulé, Health Canada, April 29, 2010).

The most common forms of supplemental calcium are calcium carbonate and calcium citrate.2 The bioavailability of the calcium in these forms is discussed below in the section titled “Other Factors Related to Calcium Nutriture.” Generally fewer tablets of calcium carbonate are required to achieve given dose of elemental calcium because calcium carbonate generally provides 40 percent elemental calcium, compared with 21 percent for calcium citrate. Thus, costs tend to be lower with calcium carbonate (Heaney et al., 2001; Keller et al., 2002) than with calcium citrate, and compliance may be higher among patients who do not want to take (or have difficulty swallowing) multiple pills. Chewable calcium carbonate supplements are also available. However, compared with calcium citrate, calcium carbonate is more often associated with gastrointestinal side effects, including constipation, flatulence, and bloating (Straub, 2007). Calcium citrate is less dependent than calcium carbonate on stomach acid for absorption (Hunt and Johnson, 1983; Recker, 1985; Straub, 2007) and thus can be taken without food. It is useful for individuals with achlorhydria, inflammatory bowel disease, or absorption disorders or who are taking histamine-2 receptor blockers or proton pump inhibitors; for residents of long-term care facilities where calcium supplements are not given with meals; and for others whose schedules preclude taking supplements with food (Bo-Linn et al., 1984; Carr and Shangraw, 1987; Straub, 2007). Calcium can compete or interfere with the absorption of iron, zinc, and magnesium. For this reason, persons with known deficiencies of these other minerals who require calcium supplementation usually take calcium supplements between meals (Straub, 2007).


Calcium is absorbed by active transport (transcellularly) and by passive diffusion (paracellularly) across the intestinal mucosa. Active transport of calcium is dependent on the action of calcitriol and the intestinal vitamin D receptor (VDR). This transcellular mechanism is activated by calcitriol and accounts for most of the absorption of calcium at low and moderate intake levels. Transcellular transport occurs primarily in the duodenum where the VDR is expressed in the highest concentration, and is dependent on up-regulation of the responsive genes including the calcium transport protein called transient receptor potential cation channel, vanilloid family member 6 or TRPV6 (Li et al., 1993; Xue and Fleet, 2009). These features—up-regulation of VDR and TRPV6—are most obvious during states in which a high efficiency of calcium absorption is required.

Passive diffusion or paracellular uptake involves the movement of calcium between mucosal cells and is dependent on luminal:serosal electrochemical gradients. Passive diffusion occurs more readily during higher calcium intakes (i.e., when luminal concentrations are high) and can occur throughout the length of the intestine (Ireland and Fordtran, 1973). However, the permeability of each intestinal segment determines passive diffusion rates. The highest diffusion of calcium occurs in the duodenum, jejunum, and ileum (Weaver and Heaney, 2006b).

From a recent series of controlled metabolic studies undertaken by the USDA, mean calcium absorption (also referred to as “fractional calcium absorption,” which is the percentage of a given dose of calcium that is absorbed) in men and non-pregnant women—across a wide age range— has been demonstrated to be approximately 25 percent of calcium intake (Hunt and Johnson, 2007). Mean urinary loss averages 22 percent and fecal loss 75 percent of total calcium intake, with minor losses from sweat, skin, hair, etc. In general, mean calcium absorption and calcium intake are directly related (Heaney et al., 1975; Gallagher et al., 1980; Hunt and Johnson, 2007). However, fractional calcium absorption varies inversely with calcium intake when the intake is very low (Malm, 1958; Spencer et al., 1969; Ireland and Fordtran, 1973). For example, when calcium intake was lowered from 2,000 to 300 mg, healthy women increased their fractional whole body retention of ingested calcium, an index of calcium absorption, from 27 percent to about 37 percent (Dawson-Hughes et al., 1993). This type of adaptation occurs within 1 to 2 weeks and is accompanied by a decline in serum calcium concentration and a rise in serum PTH and calcitriol concentrations (see section below titled “Homeostatic Regulation of Calcium”). The fraction of calcium absorbed rises adaptively as intake is lowered. However, this rise is not sufficient to offset the loss in absorbed calcium that occurs as a result of the lower intake of calcium—however modest that decrease may be—and thus net calcium absorption is reduced.

Fractional calcium absorption varies during critical periods of life. In infancy, it is high at approximately 60 percent, although the range is large (Fomon and Nelson, 1993; Abrams et al., 1997). Calcium absorption in newborns is largely passive and facilitated by the lactose content of breast milk (Kocian et al., 1973; Kobayashi et al., 1975). As the neonate ages, passive absorption declines and calcitriol-stimulated active intestinal calcium absorption becomes more important (Ghishan et al., 1980; Halloran and DeLuca, 1980; Ghishan et al., 1984).

A recent preliminary report on breast-fed infants in the first 2 months of life (Hicks et al., 2010) reported calcium absorption of approximately 33.7 ± 2.0 mg/100 kcal. In an earlier study using stable isotopes (Abrams et al., 1997), calcium absorption was measured in 14 breast milk–fed infants who were 5 through 7 months of age at the time of the study. Mean absorption was 61 ± 23 percent of intake when approximately 80 percent of the calcium intake was from human milk (IOM, 1997). There was no significant relationship between calcium intake from solid foods and the fractional calcium absorption from human milk. This finding suggests that calcium from solid foods does not negatively affect the bioavailability of calcium from human milk (IOM, 1997). Using measured urinary calcium and estimates of endogenous excretion, net retention of calcium was calculated to be 68 ± 38 mg/day for those infants. Abrams (2010) concluded that in infancy, based on calcium intakes that vary from as low as 200 mg/day in exclusively breast-fed infants in the early months of life to 900 mg/day in older formula-fed infants receiving some solids, calcium absorption depends primarily on the level of intake. The author reported that the absorption fraction can range from somewhat above 60 percent with lower intakes to about 30 percent with higher intakes. As the infant transitions into childhood, fractional calcium absorption declines, only to rise again in early puberty, a time when modeling of the skeleton is maximal. Abrams and Stuff (1994) found fractional absorption in white girls with a mean calcium intake of about 931 mg/day to average 28 percent before puberty, 34 percent during early puberty (the age of the growth spurt), and 25 percent 2 years after early puberty. Fractional absorption remains about 25 percent in young adults. In 155 healthy men and women between 20 and 75 years of age, mean calcium absorption was 24.9 ± 12.4 percent of total intake (Hunt and Johnson, 2007). During pregnancy, calcium absorption doubles (Kovacs and Kronenberg, 1997; Kovacs, 2001). Metabolic status also influences calcium absorption such that severe obesity is associated with higher calcium absorption and dieting reduces the fractional calcium absorption by 5 percent (Cifuentes et al., 2002; Riedt et al., 2006).

See more: Margarita Alvarez Project Runway, Margarita Alvarez (@Margaritaalvarezofficial)

With aging and after menopause, fractional calcium absorption has been reported to decline on average by 0.21 percent per year after 40 years of age (Heaney et al., 1989). Nordin et al. (2004) and Aloia et al. (2010) also reported decreased absorption with age. There are early reports of an inverse correlation between age and calcium absorption in women (Avioli et al., 1965), and several studies have indicated that despite an increase in circulating levels of calcitriol in older women, which would be anticipated to increase calcium uptake, fractional calcium absorption was unaffected (Bullamore et al., 1970; Alevizaki et al., 1973; Gallagher et al., 1979; Tsai et al., 1984; Eastell et al., 1991; Ebeling et al., 1992). Thus, although calcium absorption (active calcium transport) has been reported to decrease with age, it is challenging to take this factor into consideration given that calcium intake must be very high to have a significant effect on calcium uptake via the passive absorption.