Calcium

Clinical Studies
References


Calcium is essential for healthy bones, the CNS (central nervous system), muscle and cardiac function. Its deficiency is associated with cramps, headaches, fractures, tooth decay, hypertension and palpitations. Calcium citrate replaces the calcium that is lost by chelating substances.

Calcium may also be beneficial in osteoporosis, premenstrual syndrome, menstrual cramps, high blood pressure, high cholesterol, high triglycerides, depression, migraine headaches and the prevention of colorectal cancer and multiple sclerosis.

back to top

Published Clinical Studies cltop
Calcium

Interaction of dietary calcium and protein in bone health in humans.1a

Dawson-Hughes B.

 

Calcium and Bone Metabolism Laboratory at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. bees.dawson-hughes@tufts.edu

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.

Publication Types:

  • Review
  • Review, Tutorial

PMID: 12612168 [PubMed - indexed for MEDLINE]

back

Effect of calcium supplementation on blood pressure in children.2

Gillman MW, Hood MY, Moore LL, Nguyen US, Singer MR, Andon MB.

 

Evans Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Massachusetts, USA.

OBJECTIVE: To evaluate the effect of calcium supplementation on blood pressure in children. DESIGN: Randomized, double-masked, placebo-controlled trial. SETTING AND PARTICIPANTS: One hundred one fifth-grade students in one inner-city school. INTERVENTION: Each child consumed 480 ml of juice beverages, containing either no calcium or 600 mg calcium (as calcium citrate malate) daily for 12 weeks. MEASUREMENTS: At baseline we obtained nutrient data from three sets of 2-day food records on each subject. We measured blood pressure four times on each of three weekly sittings at baseline and at follow-up. Using multiple linear regression analysis, we compared mean blood pressure change in the intervention group with that in the placebo group. RESULTS: There were 50 girls and 51 boys; 61 subjects were black. At baseline, mean age was 11.0 years, systolic and diastolic blood pressures were 101.7 and 57.7 mm Hg, daily total energy intake was 1966 kcal, and calcium intake was 827 mg. With control for age, height, hours of television watched, and baseline blood pressure, systolic blood pressure increased 1.0 mm Hg in the intervention group and 2.8 mm Hg in the placebo group (effect estimate = -1.8 mm Hg; 95% confidence interval -4.0, 0.3). In black subjects the intervention effect estimate was -2.0 mm Hg (95% confidence interval -4.4, 0.4). From lowest to highest quartile of baseline calcium intake (per 1000 kcal), the intervention effect estimates were -3.5, -2.8, -1.3, and 0.0 mm Hg (p for trend = 0.009). There was little effect on diastolic blood pressure. CONCLUSION: These data suggest a blood pressure-lowering effect of calcium supplementation in children, especially in subjects with low baseline calcium intake.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial

PMID: 7636641 [PubMed - indexed for MEDLINE]

back

 3
The effect of calcium supplementation and Tanner stage on bone density, content and area in teenage women.

Lloyd T, Martel JK, Rollings N, Andon MB, Kulin H, Demers LM, Eggli DF, Kieselhorst K, Chinchilli VM.

 

Department of Obstetrics and Gynecology, College of Medicine, Pennsylvania State University, Hershey 17033, USA.

One hundred and twelve Caucasian girls, 11.9 +/- 0.5 years of age at entry, were randomized into a 24-month, double-masked, placebo-controlled trial to determine the effect of calcium supplementation on bone mineral content, bone area and bone density. Supplementation was 500 mg calcium as calcium citrate malate (CCM) per day. Controls received placebo pills, and compliance of both groups averaged 72%. Bone mineral content, bone mineral area and bone mineral density of the lumbar spine and total body were measured by dual energy X-ray absorptiometry (DXA). Calcium intake from dietary sources averaged 983 mg/day for the entire study group. The supplemented group received, on average, an additional 360 mg calcium/day from CCM. At baseline and after 24 months, the two groups did not differ with respect to anthropometric measurements, urinary reproductive hormone levels or any measurement of pubertal progression. The supplemented group had greater increases of total body bone measures: content 39.9% versus 35.7% (p = 0.01), area 24.2% versus 22.5% (p = 0.15) and density 12.2% versus 10.1% (p = 0.005). Region-of-interest analyses showed that the supplemented group had greater gains compared with the control group for bone mineral density, content and area. In particular, in the lumbar spine and pelvis, the gains made by the supplemented group were 12%-24% greater than the increases made by the control group. Bone acquisition rates in the two study groups were further compared by subdividing the groups into those with below- or above-median values for Tanner score and dietary calcium intake. In subjects with below-median Tanner scores, bone acquisition was not affected by calcium supplementation or dietary calcium level. However, the calcium supplemented subjects with above-median Tanner had higher bone acquisition rates than the placebo group with above-median Tanner scores. Relative to the placebo group, the supplemented group had increased yearly gains of bone content, area and density which represented about 1.5% of adult female values. Such increases, if held to adult skeletal maturity, could provide protection against future risk of osteoporotic fractures.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial

PMID: 8883115 [PubMed - indexed for MEDLINE]

back

 4
Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women.

Riggs BL, O'Fallon WM, Muhs J, O'Connor MK, Kumar R, Melton LJ 3rd.

 

Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

We report a 4-year randomized, double-blind, placebo-controlled clinical trial in 236 normal postmenopausal women (mean age +/- SE, 66.3+/-0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% (p < 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% (p = 0.003) at year 1 and 1.3% (p = 0.015) at year 4; and for total body bone mineral, 0.4% (p = 0.002) at year 1 and 0.9% (p = 0.017) at year 4. Similar differences at year 4 were: -18.9% (p = 0.002) for parathyroid hormone (PTH), -11.9% (p = 0.026) for serum osteocalcin, and -32.2% (p = 0.003) for urine free pyridinoline. We conclude that long-term administration of calcium supplements to elderly women partially reverses age-related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial

PMID: 9495509 [PubMed - indexed for MEDLINE]

back

Calcium as a treatment of osteoporosis.5

Blanch J, Pros A.

 

IMAS Rheumatology Service, University Hospitals del Mar and L'Esperanca, Barcelona, Spain.

The role of calcium in bone metabolism, optimal calcium intake, the use of calcium as monotherapy for osteoporosis or in combination with other drugs and the differences between various calcium salts are reviewed. Calcium is an essential element in bone mineralization and formation. There are sufficient data supporting the use of calcium in the prevention and treatment of osteoporosis and calcium in combination with vitamin D is widely used in the prevention and treatment of osteoporosis mainly in elderly patients, although its indication in postmenopausal osteoporosis is not yet clear. Numerous calcium preparations are available on the market and differ only in regard to their bioavailability. However, this difference has very little clinical significance except in patients with achlorhydria or elderly persons with low gastric secretion, in which cases pidolate and calcium citrate can be used since they are more efficiently absorbed. (c) 1999 Prous Science. All rights reserved.

PMID: 12973426 [PubMed]

back

 6
The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study.

Ruml LA, Sakhaee K, Peterson R, Adams-Huet B, Pak CY.

 

University of Texas Southwestern Medical School, Center for Mineral Metabolism and Clinical Research, Dallas, TX 75235-8891, USA.

This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial

PMID: 11329114 [PubMed - indexed for MEDLINE]

back to top

Referencesre

  1. Purwar M, Kulkarni H, Motghare V, Dhole S. Calcium supplementation and prevention of pregnancy induced hypertension. J Obstet Gynaecol Res 1996;22(5):425-30.
  2. Yamamoto ME, Applegate WB. Klag MJ, et al. Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from phase I of the trials of hypertension prevention (TOHP). Trials of Hypertension Prev (TOHP) Collab Res Group. Ann Epidemiol 1995;5(2):96-107.
  3. Petersen LJ, Rudnicki M, Hojsted J. Long-term oral calcium supplementation reduces diastolic blood pressure in end stage renal disease. A randomized, double-blind, placebo-controlled study. Int J Artif Organs 1994;17(1):37-40.
  4. Weinberger MH, Wagner UL, Fineberg NS. The blood pressure effects of calcium supplementation in humans of known sodium responsiveness. Am J Hypertens 1993;6(9):799-805.
  5. Storm D, Eslin R, Porter ES, et al. Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 1998;83(11):3817-25.
  6. Baeksgaard L, Andersen KP, Hyldstrup L. Calcium and vitamin D supplementation increases spinal BMD in healthy, postmenopausal women. Osteoporos Int 1998;8(3):255-60.
  7. Dawson-Hughes B, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337(10):670-6.
  8. Whelton PK, Kumanyika SK, Cook NR, et al. Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the trials of hypertension prevention (TOHP). Trials of Hypertension Prev (TOHP) Collab Res Group. Am J Clin Nutr 1997;65(2 Suppl):652S-60S.
  9. Kung AWC, Pun KK. Bone mineral density in premenopausal women receiving long-term physiological doses of levothyroxine. JAMA 1991;265:2688-91.
  10. Riggs BL, et al. Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 1998;13(2):168-74.
  11. Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. N Engl J Med 1997;337(2):69-76.
  12. Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prev Study Group. N Engl J Med 1999;340(2):101-7.
  13. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.
  14. Huggins C. Calcium-rich food at each meal ensures intake. New York, NY: Reuters Health, 1999. www.reutershealth.com/eline/open/1999100109.html (Accessed 4 October 1999).
  15. Young DS. Effects of Drugs on Clinical Laboratory Tests 4th ed. Washington: AACC Press, 1995.
  16. Schneider DL, Barrett-Connor EL, Morton DJ. Thyroid hormone use and bone mineral density in elderly men. Arch Intern Med 1995;155:2005-7.
  17. McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  18. Micromedex Healthcare Series. Englewood, CO: MICROMEDEX Inc.
  19. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  20. Franklyn AJ, Bettenridge J, Daykin J, et al. Long-term thyroxine treatment and bone mineral density. Lancet 1992;340:9-13.