Got Calcium? Practical Clinical Pearls
By David Kiefer, MD
Do you ever find yourself halfway through a glass of milk, knowing your mother would have been proud because it is so good for your bones and teeth? This public health message continues and has expanded to include numerous at-risk groups that may need to augment their dietary calcium intake. These recommendations have spawned an explosion in the types of calcium supplements available to meet our preventive health needs, but this may be confusing for patients and practitioners alike. What, literally, is the scoop?
Physiology
Calcium, as the most abundant mineral in the human body, functions in nerve conduction, muscle contraction, hemostasis, cell membranes, and, of course, forming bones and teeth. Ninety-nine percent of the body’s calcium is stored in the skeletal system and the rest is in an exchangeable pool.1 Calcium either exists in the serum in the metabolically active ionized form or as protein-bound complexes, and serum levels are under tight control by parathyroid hormone, calcitonin, and vitamin D.1
The average calcium intake for adults in the United States is less than 800 mg of elemental calcium per day,2 well below the estimated prehistoric intake of 1,900 mg/d.1 This is despite recent surveys in the United States that report an increase in daily calcium supplement use from 6% to 11% between 1987 and 2000.3
Foods high in calcium include sardines, dairy products (especially ricotta cheese, yogurt, milk), tofu, sesame seeds, collard greens, and soybeans. (For detailed information about nutrient contents for specific foods, visit the Food and Nutrition Information Center web site at www.nal.usda.gov/fnic/.)
Absorption/Excretion
Calcium absorption is variable and depends upon a number of factors. When calcium intake is in the average range (750 mg/d), humans absorb 25-50% of what is ingested;1 the fraction of calcium absorbed increases in low-intake situations and vice versa.4 There is also a variation in absorption percentage with age: Absorption is highest (about 60%) in infants, dropping to about 25% in young adults, with small peaks in early puberty and the last two trimesters of pregnancy.4 Calcium also behaves as a "threshold" nutrient, where beyond a certain intake (e.g., 1,000 mg/d for young adult females), there is no further effect on the body’s calcium balance.5
There are many additional factors that affect the absorption of calcium (see Table 1). Absorption occurs in the duodenum and proximal jejunum, where there is a saturable and vitamin D-dependent system more important in low-intake situations, and throughout the small bowel (especially the ileum), involving a passive and non-saturable system more important when calcium intake is high.1,4 Caffeine (such as the amount in two cups of coffee per day) may decrease both calcium absorption and increase renal calcium excretion in situations when calcium intake is less than 800 mg/d.
Table 1
Factors affecting the absorption of calcium from the gastrointestinal tract22
Calcium is lost through the skin (< 20 mg/d), and in urine (40-200 mg/d) and feces (80-120 mg/d).6 Urinary excretion of calcium may increase with diets high in sodium or protein, but it remains unproven how this translates into clinically important endpoints such as bone mineral density, osteoporosis, or fractures.4,6
Basic Intake Recommendations
Recommended intakes of vitamins and minerals were published from 1941 to 1989 as Recommended Dietary Allowances (RDA), values that were meant to meet the requirements of approximately 98% of healthy individuals of a certain age and gender.7 RDA values are useful in setting goals for individuals. More recently, the Institute of Medicine expanded on RDAs by establishing Dietary Reference Intakes (DRI), four listings that include the Recommended Dietary Allowance (RDA); the Estimated Average Requirement (EAR), a value that ensures adequacy in 50% of a particular group; the Adequate Intake (AI), used if there is not sufficient evidence to set the EAR or RDA, and representing an estimate of the average intake by a certain group of healthy people; and the Tolerable Upper Intake Level (UL), the highest level below which there is no harm to the individual.4 The National Institutes of Health (NIH) also published guidelines for the optimal intake of calcium, based upon the input of experts from many medical disciplines.8
For calcium, the Adequate Intake (AI) recommendations, compared with NIH Consensus Statement recommendations, are listed in Tables 2 and 3. The UL for calcium (all individuals, including those who are pregnant or lactating) is 2,500 mg/d; there was not enough evidence to establish an UL for infants 0-12 months old.
Table 2
Recommended daily intake of elemental
calcium (mg)
for different age groups
Table 3
Recommended daily intake of elemental calcium (mg)
for special populations
Calcium Supplement Formulations
There are many different types of calcium supplements that differ in amount of elemental calcium, bioavailability, and cost. Calcium, a cation, needs to be paired with an anion carrier molecule to make a stable tablet for human consumption. There are many anions used for this purpose (i.e., carbonate, citrate, gluconate, sulfate, citrate-malate); it is the weight of the anion molecule that determines what percentage of a calcium product is the elemental calcium. For example, carbonate is relatively light, so 40% of calcium carbonate tablets are elemental calcium, compared to 24% for calcium citrate, or 9.3% for calcium gluconate.5 To avoid confusion, when reading a product label, focus on the amount (mg) of elemental calcium for a given tablet of each product.
With respect to bioavailability, adult absorption efficiencies from most supplements average 30%-32%. One calcium form, calcium citrate-malate, is used to fortify some foods such as orange juice, and has an absorption efficiency around 35%. Several clinical trials have compared the absorption of calcium carbonate and calcium citrate. One trial found no difference in absorption when 24 postmenopausal women (23 white, one African-American; average age 56 years) were randomized to take 500 mg of elemental calcium, either as carbonate or citrate, plus 200 IU of vitamin D.9 Of note, the women were also asked to avoid all dairy to keep food calcium ingestion below 400 mg; low calcium intake situations may lead to a situation of overall enhanced calcium absorption.
In a small trial of 11 people with achlorhydria, absorption from calcium citrate was significantly better than from calcium carbonate. In the comparison group of nine people with normal gastric acid, there was no difference between citrate and carbonate absorption.10 For these reasons, some sources recommend that people who have achlorhydria either use calcium citrate or take calcium carbonate supplements with a meal.4
Another randomized study compared the effects of 1,000 mg of calcium citrate vs. calcium carbonate in 40 postmenopausal women (mean age 73 years) by measuring several physiological parameters meant to indicate bone turnover.11 Calcium citrate caused a significant decrease in all four markers of bone resorption when compared to calcium carbonate; there was no difference in serum PTH levels or urinary calcium excretion.
A recent trend has been to use calcium supplements from coral calcium (which contains calcium carbonate) obtained from the reefs off Okinawa. There are concerns about the possibility of high amounts of lead and mercury in some of the coral calcium products, as well as no proof of the other health benefits often touted with this type of calcium.12 Furthermore, other sources recommend avoiding oyster shell calcium, bone meal calcium, and dolomite calcium due to concerns about lead contamination.1
Clinical Trials
Clinical research has shown a benefit with calcium supplementation in several disease states: osteoporosis and osteoporotic fractures, colorectal cancer, and breast cancer. Calcium supplementation appears to increase bone density. One meta-analysis showed that calcium was more effective than placebo in reducing rates of bone loss in postmenopausal women.13 There was also a trend toward improvement in vertebral fracture risk. One review of clinical trials found that increased intake of calcium in postmenopausal women led to a slight decrease in fracture risk: With approximately 1,000 mg of supplemental calcium per day there was a 30% reduction in fracture risk, including a 24% decrease in hip fracture risk.15 Furthermore, one placebo-controlled trial of 1,200 mg of calcium triphosphate plus 800 IU cholecalciferol in 3,270 women (mean age 84 years) demonstrated a decreased risk (odds ratio 0.70) of fracture, including hip and other non-vertebral fractures, over 36 months of follow-up.16 The effects of calcium on bone mineral density are mediated through other variables, such as body mass index (BMI), muscle strength, gender, and age.14 For example, these variables interact in such a way that the effects of dietary calcium are most pronounced in people with a low BMI.
The associations between high calcium intake and lower cancer risks are conflicting. One double-blind, randomized, controlled trial of 930 people found a slight reduction in recurrent colorectal adenomas over four years of supplementation with calcium carbonate (1,200 mg of elemental calcium daily).17 However, a review of the epidemiological evidence of association between calcium, vitamin D, and colorectal cancer failed to find anything more than a weak, non-significant inverse relationship between calcium and colorectal cancer rates.18
For breast cancer, a cohort analysis of 88,691 women in the Nurses’ Health Study found that a high intake of low-fat dairy foods was associated with a lower risk of breast cancer in premenopausal women; this same connection was not statistically significant for postmenopausal women.19 It was difficult to determine, however, if the calcium in these dairy foods was independently associated with reduced breast cancer risks. Animal studies have demonstrated that low calcium intake can lead to increases in breast cancer depending on the type of diet: In low-fat diets, increased breast cancer rates only occur when dietary calcium is very low, but in a high-fat diet, even moderately low calcium intakes (such as found in the normal Western diet) could lead to higher breast cancer rates.20
Adverse Effects
Most calcium supplements are well tolerated, and clinical trials often report side effects as being minimal.11 Calcium carbonate can cause constipation, bloating, and gas, symptoms that can be avoided by increasing fluid intake or switching to a different preparation.2 For any calcium supplement, there may be a risk to people with calcium-containing urinary stones or with absorptive hypercalciuria, though low calcium intakes may actually increase the risk for stones (via increased urinary oxalate).2 One clinical trial studied calcium citrate (400 mg twice daily) in 18 healthy, stone-free postmenopausal women, and found no increased risk of stone formation.21
The over-use of calcium carbonate antacids (greater than approximately 4 g/d in people with impaired renal function, or 20 g/d in people with normal renal function) can lead to the "milk-alkali" syndrome, or high blood calcium levels, severe renal damage, metabolic alkalosis, and ectopic calcium deposition.8
Calcium may interfere with the absorption of many compounds including iron, zinc, bisphosphonates, and tetracycline,2 as well as quinolone antibiotics,22 sotalol,23 and levothyroxine,24 either by forming complexes with the medications or by changing the acidity of the stomach (i.e., with calcium carbonate). It seems prudent to recommend that patients separate the timing of their calcium supplements and other medications. Thiazide diuretics may act to decrease the excretion of calcium.25
There is some epidemiological evidence that calcium can increase the incidence of prostate cancer. The Physicians’ Health Study (a cohort of 20,885 male U.S. physicians) demonstrated a trend toward increased prostate cancer risk with increased calcium intake as estimated from five dairy foods; the high calcium intake group (> 600 mg/d) had a 32% higher risk of prostate cancer than did the low calcium intake group (< 150 mg/d).26 This result agrees with other epidemiological studies as well as with observations that countries with higher per capita dairy consumption also seem to have higher prostate cancer rates. The mechanism of this effect seems to be that a high calcium intake suppresses the formation of 1,25 dihydroxy vitamin D3 levels, a vitamin that otherwise inhibits the proliferation of cells in the prostate.
Conclusion
Calcium is an important mineral for many physiological processes in the human body. The average intake in the United States is less than optimal, and recommendations have been made for the ideal daily intake of elemental calcium based on age, gender, and for certain medical situations. It is important to be aware of the different factors that can aid or hinder calcium absorption, as well as the form of calcium supplements. Calcium citrate is better absorbed in cases of achlorhydria, a common problem that occurs as people age. There are important connections between calcium intake and osteoporosis, fracture risk, and cancer rates, some of the specifics of which are still being elucidated.
Recommendation
The contribution of adequate calcium intake to health and the prevention of disease is important, especially for certain ages and at-risk populations. People should focus on consuming low-fat foods high in calcium, using supplements when necessary to achieve the intake of elemental calcium recommended by the NIH Consensus Panel (see Tables 2 and 3). Calcium citrate may be better absorbed and correlate with better clinical outcomes in people with achlorhydria; otherwise, cheaper supplements such as calcium carbonate may be adequate.
Dr. Kiefer recently completed a fellowship at the Program in Integrative Medicine, College of Medicine, University of Arizona, Tucson.
References
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3. Millen AE, et al. Use of vitamin, mineral, nonvitamin, and nonmineral supplements in the United States: The 1987, 1992, and 2000 National Health Interview Survey results. J Am Diet Assoc 2004;104:942-950.
4. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997.
5. Anderson JJB, Garner SC. Dietary Issues of Calcium and Phosphorus. In: Anderson JJB, Garner SC, eds. Calcium and Phosphorus in Health and Disease. Boca Raton, FL: CRC Press; 1995.
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7. National Research Council (U.S.). Subcommittee on the Tenth Edition of the RDAs. Recommended Dietary Allowances. 10th ed. Washington, DC: National Academy Press; 1989.
8. Optimal Calcium Intake. NIH Consensus Statement. 1994; 12:1-31.
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11. Kenny AM, et al. Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women. Osteoporos Int 2004; 15:290-294.
12. Blumberg S. Is coral calcium a safe and effective supplement? J Am Diet Assoc 2004;104:1335-1336.
13. Shea B, et al. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev 2004(1):CD004526.
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15. Cumming RG, Nevitt MC. Calcium for prevention of osteoporotic fractures in postmenopausal women. J Bone Miner Res 1997;12:1321-1329.
16. Chapuy MC, et al. Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 1994;308:1081-1082.
17. Baron JA, et al. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 1999;340:101-107.
18. Martinez ME, Willett WC. Calcium, vitamin D, and colorectal cancer: A review of the epidemiologic evidence. Cancer Epidemiol Biomarkers Prev 1998;7:163-168.
19. Shin MH, et al. Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst 2002; 94:1301-1311.
20. Lipkin M, Newmark HL. Vitamin D, calcium and prevention of breast cancer: A review. J Am Coll Nutr 1999;18: 392S-397S.
21. Sakhaee K, et al. Stone forming risk of calcium citrate supplementation in health postmenopausal women. J Urol 2004;172:958-961.
22. Murray JJ, Healy MD. Drug-mineral interactions: A new responsibility for the hospital dietitian. J Am Diet Assoc 1991;91:66-70, 73.
23. Kahela P, et al. Effect of food, food constituents and fluid volume on the bioavailability of sotalol. Acta Pharmacol Toxicol 1979;44:7-12.
24. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750.
25. Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-556.
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27. Boyle P, et al. The epidemiology of prostate cancer. Urol Clin North Am 2003;30:209-217.
Kiefer D. Got calcium? Practical clinical pearls. Altern Med Alert 2004;7(12):140-143.
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