Vitamin Expert

Calcium Facts

Calcium has vital functions within cells in all living creatures, predominantly as a second messenger transmitting signals between the plasma membrane and the intracellular machinery. Extracellular calcium is also an essential cofactor in clotting factors and adhesion molecules and is essential for the proper formation of bone. There is recent evidence that calcium has direct effects through a membrane-spanning calcium receptor that is coupled to intracellular signalling. This receptor has been found in the parathyroid gland, the kidney, and the brain, among other tissues (1-3)

More than 99% of the calcium in the human body is in the bones and teeth. In bone, calcium provides the structural strength that allows the bone to support the body’s weight and anchor the muscles. Bone calcium also serves as a reservoir that can be tapped to maintain extracellular calcium concentration regardless of intake. Calcium differs from most other nutrients in that the body contains a substantial store, far in excess of short-term needs, but at the same time that store serves a critical structural role. Thus the effects of calcium deficiency may escape notice for a considerable time, until they manifest as skeletal weakness or fractures.

Calcium homeostasis is maintained in part by complex hormonal systems that serve to keep the extracellular fluid calcium concentration within fairly narrow ranges by regulating the absorption, excretion, and redistribution of calcium and other minerals by the body.

When extracellular fluid ionized calcium concentration drops sufficiently below the regulated set point, hyperexcitation of cells occurs, with extreme hyperexcitation resulting in tetany and possibly death. When extracellular fluid ionized calcium concentration rises, cell firing is reduced, especially in muscle and nerve tissue. This can lead to reduced intestinal motility (constipation), lethargy, and mental confusion. Calcium balance (intake minus the sum of all losses) generally is positive during growth, is essentially zero in the mature adult, and then becomes negative with advancing age. Negative calcium balance can arise from low intake, poor absorption, high obligatory losses, or any combination of these factors and will inevitably lead to bone loss if not corrected. There are many factors that increase the susceptibility of the older adult to negative calcium balance: Both intake and absorption decline, excretion increases, and bone resorption becomes greater than bone formation. The body’s ability to adapt to different calcium intakes through the calciotropic hormone systems decreases with age until it is essentially non-existent at an age of about 80 years.

There are two mechanisms of calcium absorption from the intestinal tract: (1) a paracellular, unregulated, non-saturable mechanism that predominates at high calcium intakes and (2) a transcellular, saturable, active-transport mechanism that predominates at low calcium intakes. The paracellular mechanism results in a low proportion of dietary calcium absorption, although at high intakes the absolute amount of absorbed calcium may be large. With the transcellular mechanism the total amount of calcium that can be absorbed is limited. The active calcium transport system is vitamin D dependent and involves synthesis of a calcium-binding protein.

With strenuous athletic exertion accompanied by high sweat loss, and dermal calcium losses can be significantly higher; measurable bone loss can occur across a competitive playing season (4). Urinary loss of calcium is regulated through the actions of the calciotropic hormones parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, and calcitonin, but it also depends on protein and sodium intake.

Sources of calcium

Several chemicals in foods have been found to affect the absorption of calcium. For example, phytates and oxalates form highly stable and largely indigestible complexes with calcium that greatly reduce calcium’s bioavailability (5,6). The fractional absorption of calcium from high-phytate soybean products is significantly less than that from low-phytate soybean products. Spinach contains high concentrations of calcium, but because spinach also contains high concentrations of oxalates that calcium is largely unavailable. Kale, in contrast, has high calcium and low oxalate concentrations, making the leafy green vegetable a good source of dietary calcium. Still, it takes 4 to 5 half-cup servings of kale or broccoli to equal the calcium content of a single 8-ounce glass of milk. High sodium intake increases urinary calcium excretion in adults and in elderly men and women. Urinary sodium excretion is an important determinant of urinary calcium excretion in children and adolescents.

Protein is necessary for bone and muscle health. Increased protein in the diet also increases the absorption of calcium from the gut (7); however, it also increases the obligatory calcium loss. A doubling of protein intake with all other nutrients remaining constant results in an increase in urinary calcium loss of about 50%. Part of the increase in calcium loss is due to an increased glomerular filtration rate, but high protein intake also reduces reabsorption of calcium. These changes are thought to be due to the increased acid load from a high-protein diet. The addition of fruits and vegetables to the diet can ameliorate this loss by buffering the acid load from protein.

A dietary calcium/phosphorus intake ratio >1 is associated with higher bone mass in young women (8); however, some have suggested that the form of phosphate in the diet is more important than the quantity, with acidic phosphate leading to increased urinary calcium loss analogous to the loss associated with protein intake.

Calcium is also a threshold nutrient; that is, below the threshold level, an increase in dietary calcium intake results in an improved response. Above the threshold intake, however, there is little or no further improvement. This fact complicates the interpretation of many studies of the effects of calcium intake on health, because populations in which the calcium intakes straddle the threshold will exhibit a heterogeneous dose-response curve. Finally, health problems related to chronic under nutrition of calcium are in the main slowly developing and multifactorial conditions that are difficult to pin down to any single cause.

Calcium in health and disease


Bone is continually being remodeled, with osteoclasts resorbing bone and osteoblasts replacing the absorbed bone. In general, these two processes are in equilibrium. Bone remodeling serves to repair microdamage and to allow bone to respond and adapt to mechanical stress. Older bone becomes more brittle and thus more susceptible to fracture. Bone re-modelling also aids in maintaining extracellular fluid calcium homeostasis.

At any given time some fraction of the bone surface contains resorption cavities. This “missing bone,” from which calcium has been released into the extracellular fluid, is termed the re-modelling space. (9) If the bone re-modelling rate increases, the re-modelling space increases and total bone mineral content decreases. If the bone re-modelling rate decreases, the opposite happens. This is reversible bone mineral loss or gain.

In the mature adult, bone formation often does not replace 100% of the resorbed bone. This imbalance between resorption and formation is dependent on age, hormones, and calcium intake. For example, the number of osteoblasts decreases with age, whereas low oestrogen level and low dietary calcium intake both increase osteoclast formation. Low oestrogen concentration also increases the depth of the resorption cavity, which can lead to perforation and disconnection of trabeculae. This latter type of bone loss is irreversible and has serious negative consequences for bone strength.


Osteoporosis is characterized by bone fragility such that fractures can occur under conditions of minimal trauma, including the normal stresses of living. Osteoporosis is generally a disease of older adults because the cumulative effects of slow bone mineral loss take time to deplete the skeleton. The morbidity and mortality associated with osteoporosis are related to fractures. The increased incidence of fractures in the elderly population arises from a number of different factors, but skeletal fragility is certainly important. Bone strength can be negatively affected by reduced bone mass, poor bone architecture (eg, reduced trabecular connectivity), and accumulating fatigue damage (10). All are multifactorial conditions; however, low calcium intake can be a key element. Bone mineral content can be affected by exercise; however, physical activity appears to increase bone mass only at calcium intakes >1000 mg/d, providing further evidence of calcium’s threshold nature (11).

Bone mass in old age is determined by peak bone mass and the subsequent rate of bone loss. Osteoporosis is increasingly being viewed as a paediatric disease with geriatric consequences. This view stems from the facts that 90% of bone mass is attained before age 20 years and that bone mass generally peaks before the age of 30 years (12). Deposition of calcium into bone in women decreases markedly after menarche (13) Dietary calcium intake, especially early in life, is positively associated with bone mass (14,15). Maximizing the likelihood of individuals’ attaining their genetically determined peak bone masses is an important step in reducing the incidence of osteoporosis.  Bone loss is normally minimal until the age of 40 years, after which it gradually increases with age. Bone loss in older adults is associated with low calcium intake, vitamin D insufficiency, and low androgen status. In women there is a dramatic increase in bone loss during the five years immediately after menopause.  More than five years after menopause (or after cessation of hormone replacement therapy), the rate of bone loss decreases; at this time calcium supplementation has been shown to be effective at reducing bone loss (16), especially in conjunction with vitamin D supplementation (17,18).  Combination therapies that include calcium, vitamin D, and, for women, hormone replacement therapy are the most efficacious at reducing or even reversing bone loss in older adults (19).


The term human foetus contains approximately 30 g calcium, all of which must come from maternal sources and most of which is transported during the last trimester. Calcium metabolism during pregnancy differs from that of the non-pregnant state in important ways. During pregnancy, intestinal absorption of calcium is markedly increased, probably in response to a significant increase in circulating levels of 1,25-dihydroxyvitamin D, some of which is placental in origin (20). Urinary excretion of calcium is increased, reflecting the increased absorption and also the increased renal plasma flow related to the expanded plasma volume during pregnancy. Serum calcitonin level is elevated, which may serve to protect the maternal skeleton from excessive resorption of calcium.   The increased absorption of dietary calcium would appear sufficient to provide the necessary calcium for the foetus in vitamin D–sufficient women.

Calcium, lactation, and bone

Lactating women secrete approximately 210 mg/d calcium in breast milk.78 Breast milk contains sufficient minerals to support bone growth in term infants but may not provide adequate vitamin D, especially if mothers are not receiving adequate sun exposure or dietary vitamin D. Intestinal calcium absorption during lactation decreases from the elevated level during pregnancy and is essentially the same as in the non-reproductive state (21,22).

Unlike postmenopausal bone loss, the loss of bone caused by lactation is transient. After weaning, the intestinal calcium absorption increases, urinary calcium excretion remains low, and the rate of bone re-modelling decreases. There is evidence that these changes are linked to the resumption of menses (23). The loss of bone mineral has largely been reversed by one year post-partum, even if a second pregnancy occurs during that period.


Epidemiologic evidence implicates low calcium intake in the increased incidence of both hypertension and pre-eclampsia. An inverse relationship between dietary calcium intake and blood pressure status has been found in many studies (24). Hypertension is often associated with hypercalciuria. The calciotropic hormones may also play a role. For example, seasonal changes in blood pressure correlate with seasonal changes in vitamin D status.  Low serum calcium concentration has been suggested to increase intracellular calcium concentration in vascular smooth muscle cells, which in turn increases vascular resistance (25).

Recent evidence suggests that diets high in low-fat dairy products, fruits, and vegetables and thus moderate to high in calcium content are efficacious in reducing blood pressure and preventing hypertension. Calcium supplementation decreased diastolic blood pressure in African American adolescents. The effect was greater among those subjects with lower habitual calcium intakes. If dietary calcium intake does reduce blood pressure, this might have additional beneficial effects on offspring because maternal blood pressure and low calcium intake are risk factors for hypertension in children.

Until recently, the only empiric evidence that low calcium intake was associated with a greater risk of pre-eclampsia came from epidemiologic studies and small trials with insufficient discriminatory power. A meta-analysis of those trials concluded that calcium supplementation did have a beneficial effect (26). However, the results of the Calcium for Pre-eclampsia Prevention trial dispute that conclusion (27). That study found no significant effect of calcium supplementation on pregnancy-related hypertension, pre-eclampsia, or other pregnancy-related outcomes, although the incidences of hypertension and pre-eclampsia were numerically lower in the calcium-supplemented group.

However, the Calcium for Preeclampsia Prevention population was healthier than the general US population and also had higher calcium intakes. Many of the women in the Calcium for Pre-eclampsia Prevention study had habitual calcium intakes above the threshold intake for maximal calcium balance.


Women who exhibit common symptoms of pre-menstrual syndrome have lower serum concentrations of ionized calcium and 25-hydroxyvitamin D and higher concentrations of intact PTH than do symptom-free women (28). Calcium supplementation has been shown to reduce the symptoms of pre-menstrual syndrome (29,30). Women with pre-menstrual syndrome also have lower bone mass. Thus pre-menstrual syndrome could serve as an indicator of subclinical vitamin D deficiency, low calcium intake, and a higher risk for low bone mass and eventual osteoporosis. An increase in calcium intake among women with pre-menstrual syndrome might have significant health benefits beyond the simple reduction of pre-menstrual syndrome symptoms.

  1. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters al. Nature 1993;366: 575-80.
  2. Riccardi D, Park J, Lee WS, Gamba G, et al. Proc Natl Acad Sci U S A 1995;92:131-5.
  3. Rogers KV, Dunn CK, Hebert SC, Brown EM.  Brain Res 1997;744:47-56.
  4. Klesges RC, Ward KD, Shelton ML, Applegate WB, et al.  JAMA 1996;276:226-30.
  5. Heaney RP, Weaver CM, Recker RR.  Am J Clin Nutr 1988;47:707-9.
  6. Heaney RP, Weaver CM, Fitzsimmons ML.  Am J Clin Nutr 1991;53:741-4
  7. Kerstetter JE, O’Brien KO, Insogna KL. Am J Clin Nutr 1998;68:859-65
  8. Teegarden D, Lyle RM, McCabe GP, et al. Am J Clin Nutr 1998;68:749-54.
  9. Heaney RP.  J Bone Miner Res 1994;9:1515-23.
  10. Heaney RP.  Annu Rev Nutr 1993;13:287-316.
  11. Specker B.  J Bone Miner Res 1996;11:1539-44.
  12. Recker RR, Davies KM, et al. JAMA 1992;268: 2403-8.
  13. Abrams SA, O’Brien KO, Stuff JE. J Clin Endocrinol Metab 1996;81:2017-20.
  14. Nieves JW, Golden AL, Siris E, Kelsey JL, Lindsay R. Am J Epidemiol 1995;141:342-51.
  15. Holbrook TL, Barret-Conner E, Wingard DL.  Lancet 1988;2:1046-9.
  16. Dawson-Hughes B.  Am J Clin Nutr 1991;54 Suppl 1:274S-80S.
  17. Chapuy MC, Arlot ME,  et al. N Engl J Med 1992;327:1637-42.
  18. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. N Engl J Med 1997;337:670-6.
  19. Nieves JW, Komar L, Cosman F, Lindsay R.  Am J Clin Nutr 1998;67:18-24.
  20. Kovacs CS, Kronenberg HM. Endocr Rev 1998;18:832-72.
  21. Cross NA, Hillman LS, Allen SH, Krause GF.  J Bone Miner Res 1995;10:1312-20.
  22. Ritchie LD, Fung EB, Halloran BP, et al. Am J Clin Nutr 1998;67:693-701.
  23. Kalkwarf HJ, Specker BL, Bianchi DC, Ranz J, Ho M. N Engl J Med 1997;337:523-8.
  24. Morris CD, Reusser ME. Semin Nephrol 1995;15:490-5.
  25. Repke JT, Robinson JN. Int J Gynaecol Obstet 1998;62:1-9.
  26. Bucher HC, Guyatt GH, et al.  JAMA 1996;275:1113-7.
  27. Levine RJ, Hauth JC, Curet LB, et al. N Engl J Med 1997;337:69-76.
  28. Penland JG, Johnson PE. Am J Obstet Gynecol 1993;168:1417-23.
  29. Thys-Jacobs S, Alvir J.  J Clin Endocrinol Metab 1995;80:2227-32.
  30. Lee SJ, Kanis JA.  Bone 1994;24:127-34.