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April 3, 1996, Vol 275, No. 13 >
ARTICLE | April 3, 1996

Effects of Dietary Calcium Supplementation on Blood Pressure: Title and subTitle BreakA Meta-analysis of Randomized Controlled Trials FREE

Heiner C. Bucher, MD; Richard J. Cook, PhD; Gordon H. Guyatt, MD, MSc; Jefferey D. Lang, MD, FRCPC; Deborah J. Cook, MD, FRCPC; Rose Hatala, MD, FRCPC; Dereck L. Hunt, MD
[+] Author Affiliations

Reprints: Gordon H. Guyatt, MD, MSc, Department of Clinical Epidemiology and Biostatistics, Room 2C10, McMaster University Medical Center, 1200 Main St W, Hamilton, Ontario, Canada L8N 3Z5.


JAMA. 1996;275(13):1016-1022. doi:10.1001/jama.1996.03530370054031
Text Size: A A A
Published online
Article
References

Objective.  —To review the effect of supplemental calcium on blood pressure.

Data Source.  —We searched MEDLINE and EMBASE for 1966 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials.

Study Selection.  —We included any study in which investigators randomized people to calcium supplementation or placebo and measured blood pressure for at least 2 weeks. Fifty-six articles met the inclusion criteria, and 33 were eligible for analysis, involving a total of 2412 patients.

Data Extraction.  —Two pairs of independent reviewers abstracted data and assessed validity according to six quality criteria.

Data Synthesis.  —We calculated the differences in blood pressure change between the calcium supplementation group and the control group and pooled the estimates, with each trial weighted with the inverse of the variance using a random-effects model. Predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodological quality of the studies. The pooled analysis showed a reduction in systolic blood pressure of -1.27 mm Hg (95% confidence interval [CI], -2.25 to -0.29 mm Hg; P=.01) and in diastolic blood pressure of -0.24 mm Hg (95% CI, -0.92 to 0.44 mm Hg; P=.49). None of the possible mediators of blood pressure reduction explained differences in treatment effects.

Conclusions.  —Calcium supplementation may lead to a small reduction in systolic but not diastolic blood pressure. The results do not exclude a larger, important effect of calcium on blood pressure in subpopulations. In particular, further studies should address the hypothesis that inadequate calcium intake is associated with increased blood pressure that can be corrected with calcium supplementation.(JAMA. 1996;275:1016-1022)

REFERENCES

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2 +
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3 +
Resnick LM.  Calcium and hypertension: the emerging connection. Ann Intern Med . 1985;;103:944-946.
4 +
Cappuccio FP, Elliott P, Allender PS, Pryer J, Follman DA, Cutler JA.  The epidemiological association between dietary calcium intake and blood pressure: a meta-analysis of published data. Am J Epidemiol . 1995;;142:935-945.
5 +
Dumas P, Tremblay J, Hamet P.  Stress modulation by electrolytes in salt-sensitive spontaneously hypertensive rats. Am J Med Sci . 1995;;307( (suppl 1) ):S130-S137.
6 +
National High Blood Pressure Education Program Working Group.  National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch Intern Med . 1993;; 153:186-208.
7 +
NIH Consensus Development Panel on Optimal Calcium Intake.  Optimal calcium intake. JAMA . 1994;; 272:1942-1948.
8 +
Cutler JA, Brittain E.  Calcium and blood pressure: an epidemiologic perspective. Am J Hypertens . 1990;;3( (suppl) ):137S-146S.
9 +
Cappuccio FP, Siani A, Strazzullo P.  Oral calcium supplementation and blood pressure: an overview of randomized controlled trials. J Hypertens . 1989;;7: 941-946.
10 +
Hamet P. The Evaluation of the Scientific Evidence for a Relationship Between Calcium and Hypertension . Rosemont, Ill: United Dairy Industry Association; 1993;:A1-A58.
11 +
Bucher HC, Guyatt GH, Cook RJ, et al.  Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials. JAMA . In press.
12 +
Dickersin K, Scherer R, Lefebvre C.  Identification of relevent studies for systematic reviews. BMJ . 1994;;309:1286-1291.
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Dickersin K.  The existence of publication bias and risk factors for its occurrence. JAMA . 1990;;263: 1385-1389.
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Oxman AD, Guyatt GH.  Validation of an index of the quality of review articles. J Clin Epidemiol . 1991;; 44:1271-1278.
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Chalmers TC, Smith HJ, Blackburn B, et al.  A method for assessing the quality of a randomized control trial. Control Clin Trials . 1981;;2:31-49.
17 +
Schulz KF, Chalmers I, Hayes RJ, Altman G.  Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;;273: 408-412.
18 +
Fleiss JL.  The statistical basis of meta-analysis. Stat Methods Med Res . 1993;;2:121-145.
19 +
Kynast-Gales SA, Massey LK.  Effects of dietary calcium from dairy products on ambulatory blood pressure in hypertensive men. J Am Diet Assoc . 1992;;92:1497-1501.
20 +
Vinson JA, Mazur T, Bose P.  Comparison of different forms of calcium on blood pressure of normotensive young males. Nutr Rep Int . 1987;;36:497-505.
21 +
Morris CD, Karanja N, McCarron DA.  Dietary versus supplemental calcium to reduce blood pressure. Clin Res . 1988;;36:A139. Abstract.
22 +
Nowson C, Morgan T.  Effect of calcium carbonate on blood pressure. J Hypertens . 1986;;4( (suppl 6) ): S673-S675.
23 +
Galloe AM, Graudal N, Moller J, Bro H, Jorgensen M, Christensen HR.  Effect of oral calcium supplementation on blood pressure in patients with previously untreated hypertension: a randomised, double-blind, placebo-controlled, crossover study. J Hum Hypertens . 1993;;7:43-45.
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Tanji JL, Lewey, Wong GY, Treguboff C, Ward JA, Amsterdam EA.  Dietary calcium supplementation as a treatment for mild hypertension. J Am Board Fam Pract . 1991;;4:145-150.
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Margetts BM, Beilin LJ, Vandongen R, Armstrong BK.  Vegetarian diet in mild hypertension: a randomised controlled trial. BMJ . 1986;;293:1468-1471.
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Siani A, Strazzullo P, Guglielmi S, et al.  Controlled trial of low calcium versus high calcium intake in mild hypertension. J Hypertens . 1988;;6:253-256.
27 +
Meese RB, Gonzales DG, Casparian JM, Ram CV, Pak CM, Kaplan NM.  The inconsistent effects of calcium supplements upon blood pressure in primary hypertension. Am J Med Sci . 1987;;294:219-224.
28 +
Cappuccio FP, Markandu ND, Singer DR, Smith SJ, Shore AC, MacGregor GA.  Does oral calcium supplementation lower high blood pressure? a double blind study. J Hypertens . 1987;;5:67-71.
29 +
Grobbee DE, Hofman A.  Effect of calcium supplementation on diastolic blood pressure in young people with mild hypertension. Lancet . 1986;;2:703-707.
30 +
Strazzullo P, Siani A, Gugliemi S, et al.  Controlled trial of long-term oral calcium supplementation in essential hypertension. Hypertension . 1986;; 8:1084-1088.
31 +
McCarron DA, Morris CD.  Blood pressure response to oral calcium in persons with mild to moderate hypertension: a randomized, double-blind, placebo-controlled, crossover trial. Ann Intern Med . 1985;; 103:825-831.
32 +
Pan WH, Wang CY, Li LA, Kao LS, Yeh SH.  No significant effect of calcium and vitamin D supplementation on blood pressure and calcium metabolism in elderly Chinese. Chin J Physiol . 1993;;36:85-94.
33 +
Lyle RM.  Does baseline serum total calcium level influence the blood pressure response to calcium supplementation? a double-blind study. Neth J Med . 1992;;41:48-55.
34 +
Van Beresteijn EC, van Schaik M, Schaafsma G.  Milk: does it affect blood pressure? a controlled intervention study. J Intern Med . 1990;;228:477-482.
35 +
Thomsen K, Nilas L, Christiansen C.  Dietary calcium intake and blood pressure in normotensive subjects. Acta Med Scand . 1987;;222:51-56.
36 +
Lyle RM, Melby CL, Hyner GC, Edmondson JW, Miller JZ, Weinberger MH.  Blood pressure and metabolic effects of calcium supplementation in normotensive white and black men. JAMA . 1987;;257: 1772-1776.
37 +
Johnson NE, Smith EL, Freudenheim JL.  Effects on blood pressure of calcium supplementation of women. Am J Clin Nutr . 1985;;42:12-17.
38 +
Weinberger MH, Wagner UL, Fineberg NS.  The blood pressure effects of calcium supplementation in humans of known sodium responsiveness. Am J Hypertens . 1993;;6:799-805.
39 +
Jespersen B, Brock A, Pedersen EB.  Lack of effect of calcium carbonate supplementation on 24 h blood pressure, angiotensin II reactivity and PTH (1-84) in essential hypertension. J Hum Hypertens . 1993;;7:103-104.
40 +
Singh RB, Rastogi SS, Singh NK, Ghosh S, Gupta S, Niaz MA.  Can guava fruit intake decrease blood pressure and blood lipids? J Hum Hypertens . 1993;; 7:33-38.
41 +
Cutler JA, Whelton PK, Appel L, et al.  The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, phase I. JAMA . 1992;;267:1213-1220.
42 +
Bierenbaum ML, Wolf E, Bisgeier G, Maginnis WP.  Dietary calcium: a method of lowering blood pressure. Am J Hypertens . 1988;;1( (suppl) ):149S-152S.
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Sunderrajan S, Bauer JH.  Oral calcium supplementation does not alter blood pressure or vascular response in normotensive men. Circulation . 1984;;70 ( (suppl 2) ):II-130. Abstract 519.
44 +
Zoccali C, Mallamaci F, Delfino D, et al.  Does calcium have a dual effect on arterial pressure? response to 1,25 dihydroxy vitamin D3 and calcium supplements in essential hypertension. J Hypertens . 1987;;5( (suppl 5) ):S267-S269.
45 +
Siani A, Strazzullo P, Guglielmi S, Mancini M.  Clinical studies of the effects of different oral calcium intakes in essential hypertension. J Hypertens . 1987;; 5( (suppl 5) ):S311-S313.
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Orwoll ES, Oviatt S.  Relationship of mineral metabolism and long-term calcium and cholecalciferol supplementation to blood pressure in normotensive men. Am J Clin Nutr . 1990;;52:717-721.
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Rouse IL, Beilin LJ, Mahoney DP, et al.  Nutrient intake, blood pressure, serum and urinary prostaglandins and serum thromboxane B2 in a controlled trial with a lacto-ovo-vegetarian diet. J Hypertens . 1986;;4:241-250.
48 +
Resnick LM, DiFabio B, Marion R, James GD, Laragh JH.  Dietary calcium modifies the pressor effects of dietary salt intake in essential hypertension. J Hypertens . 1986;;4( (suppl 6) ):S679-S681.
49 +
van Beresteyn E, Schaafsma G, de Waard H.  Oral calcium and blood pressure: a controlled intervention trial. Am J Clin Nutr . 1986;;44:883-888.
50 +
Zoccali C, Mallamaci F, Delfino D, et al.  Double-blind randomized, crossover trial of calcium supplementation in essential hypertension. J Hypertens . 1988;;6:451-455.
51 +
Zhou C, Fan S, Zhou L, Ni Y, Huang T, Shi Y.  Clinical observation of treatment of hypertension with calcium. Am J Hypertens . 1994;;7:363-367.
52 +
Hakala P, Karvetti RL.  Weight reduction on lactovegetarian and mixed diets: changes in weight, nutrient intake, skinfold thicknesses and blood pressure. Eur J Clin Nutr . 1989;;43:421-430.
53 +
Takagi Y, Fukase M, Takata S, Fujimi T, Fujita T.  Calcium treatment of essential hypertension in elderly patients evaluated by 24 H monitoring. Am J Hypertens . 1991;;4:836-839.
54 +
Lind L, Wengle B, Wide L, Sorensen OH, Ljunghall S.  Hypertension in primary hyperparathyroidism: reduction of blood pressure by long-term treatment with vitamin D (alphacalcidol): a double-blind, placebo-controlled study. Am J Hypertens . 1988;;1: 397-402.
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Figures

Tables

Interactive Graphics

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
 The Working Group on Hypertension in the Elderly. Statement on hypertension in the elderly. JAMA . 1986;;256:70-74.
2 +
McCarron DA, Morris CD.  The calcium deficiency hypothesis of hypertension. Ann Intern Med . 1987;;107:919-922.
3 +
Resnick LM.  Calcium and hypertension: the emerging connection. Ann Intern Med . 1985;;103:944-946.
4 +
Cappuccio FP, Elliott P, Allender PS, Pryer J, Follman DA, Cutler JA.  The epidemiological association between dietary calcium intake and blood pressure: a meta-analysis of published data. Am J Epidemiol . 1995;;142:935-945.
5 +
Dumas P, Tremblay J, Hamet P.  Stress modulation by electrolytes in salt-sensitive spontaneously hypertensive rats. Am J Med Sci . 1995;;307( (suppl 1) ):S130-S137.
6 +
National High Blood Pressure Education Program Working Group.  National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch Intern Med . 1993;; 153:186-208.
7 +
NIH Consensus Development Panel on Optimal Calcium Intake.  Optimal calcium intake. JAMA . 1994;; 272:1942-1948.
8 +
Cutler JA, Brittain E.  Calcium and blood pressure: an epidemiologic perspective. Am J Hypertens . 1990;;3( (suppl) ):137S-146S.
9 +
Cappuccio FP, Siani A, Strazzullo P.  Oral calcium supplementation and blood pressure: an overview of randomized controlled trials. J Hypertens . 1989;;7: 941-946.
10 +
Hamet P. The Evaluation of the Scientific Evidence for a Relationship Between Calcium and Hypertension . Rosemont, Ill: United Dairy Industry Association; 1993;:A1-A58.
11 +
Bucher HC, Guyatt GH, Cook RJ, et al.  Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials. JAMA . In press.
12 +
Dickersin K, Scherer R, Lefebvre C.  Identification of relevent studies for systematic reviews. BMJ . 1994;;309:1286-1291.
13 +
Dickersin K.  The existence of publication bias and risk factors for its occurrence. JAMA . 1990;;263: 1385-1389.
14 +
Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical Epidemiology: A Basic Science for Clinical Medicine . 2nd ed. Boston, Mass: Little Brown & Co Inc; 1991;.
15 +
Oxman AD, Guyatt GH.  Validation of an index of the quality of review articles. J Clin Epidemiol . 1991;; 44:1271-1278.
16 +
Chalmers TC, Smith HJ, Blackburn B, et al.  A method for assessing the quality of a randomized control trial. Control Clin Trials . 1981;;2:31-49.
17 +
Schulz KF, Chalmers I, Hayes RJ, Altman G.  Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;;273: 408-412.
18 +
Fleiss JL.  The statistical basis of meta-analysis. Stat Methods Med Res . 1993;;2:121-145.
19 +
Kynast-Gales SA, Massey LK.  Effects of dietary calcium from dairy products on ambulatory blood pressure in hypertensive men. J Am Diet Assoc . 1992;;92:1497-1501.
20 +
Vinson JA, Mazur T, Bose P.  Comparison of different forms of calcium on blood pressure of normotensive young males. Nutr Rep Int . 1987;;36:497-505.
21 +
Morris CD, Karanja N, McCarron DA.  Dietary versus supplemental calcium to reduce blood pressure. Clin Res . 1988;;36:A139. Abstract.
22 +
Nowson C, Morgan T.  Effect of calcium carbonate on blood pressure. J Hypertens . 1986;;4( (suppl 6) ): S673-S675.
23 +
Galloe AM, Graudal N, Moller J, Bro H, Jorgensen M, Christensen HR.  Effect of oral calcium supplementation on blood pressure in patients with previously untreated hypertension: a randomised, double-blind, placebo-controlled, crossover study. J Hum Hypertens . 1993;;7:43-45.
24 +
Tanji JL, Lewey, Wong GY, Treguboff C, Ward JA, Amsterdam EA.  Dietary calcium supplementation as a treatment for mild hypertension. J Am Board Fam Pract . 1991;;4:145-150.
25 +
Margetts BM, Beilin LJ, Vandongen R, Armstrong BK.  Vegetarian diet in mild hypertension: a randomised controlled trial. BMJ . 1986;;293:1468-1471.
26 +
Siani A, Strazzullo P, Guglielmi S, et al.  Controlled trial of low calcium versus high calcium intake in mild hypertension. J Hypertens . 1988;;6:253-256.
27 +
Meese RB, Gonzales DG, Casparian JM, Ram CV, Pak CM, Kaplan NM.  The inconsistent effects of calcium supplements upon blood pressure in primary hypertension. Am J Med Sci . 1987;;294:219-224.
28 +
Cappuccio FP, Markandu ND, Singer DR, Smith SJ, Shore AC, MacGregor GA.  Does oral calcium supplementation lower high blood pressure? a double blind study. J Hypertens . 1987;;5:67-71.
29 +
Grobbee DE, Hofman A.  Effect of calcium supplementation on diastolic blood pressure in young people with mild hypertension. Lancet . 1986;;2:703-707.
30 +
Strazzullo P, Siani A, Gugliemi S, et al.  Controlled trial of long-term oral calcium supplementation in essential hypertension. Hypertension . 1986;; 8:1084-1088.
31 +
McCarron DA, Morris CD.  Blood pressure response to oral calcium in persons with mild to moderate hypertension: a randomized, double-blind, placebo-controlled, crossover trial. Ann Intern Med . 1985;; 103:825-831.
32 +
Pan WH, Wang CY, Li LA, Kao LS, Yeh SH.  No significant effect of calcium and vitamin D supplementation on blood pressure and calcium metabolism in elderly Chinese. Chin J Physiol . 1993;;36:85-94.
33 +
Lyle RM.  Does baseline serum total calcium level influence the blood pressure response to calcium supplementation? a double-blind study. Neth J Med . 1992;;41:48-55.
34 +
Van Beresteijn EC, van Schaik M, Schaafsma G.  Milk: does it affect blood pressure? a controlled intervention study. J Intern Med . 1990;;228:477-482.
35 +
Thomsen K, Nilas L, Christiansen C.  Dietary calcium intake and blood pressure in normotensive subjects. Acta Med Scand . 1987;;222:51-56.
36 +
Lyle RM, Melby CL, Hyner GC, Edmondson JW, Miller JZ, Weinberger MH.  Blood pressure and metabolic effects of calcium supplementation in normotensive white and black men. JAMA . 1987;;257: 1772-1776.
37 +
Johnson NE, Smith EL, Freudenheim JL.  Effects on blood pressure of calcium supplementation of women. Am J Clin Nutr . 1985;;42:12-17.
38 +
Weinberger MH, Wagner UL, Fineberg NS.  The blood pressure effects of calcium supplementation in humans of known sodium responsiveness. Am J Hypertens . 1993;;6:799-805.
39 +
Jespersen B, Brock A, Pedersen EB.  Lack of effect of calcium carbonate supplementation on 24 h blood pressure, angiotensin II reactivity and PTH (1-84) in essential hypertension. J Hum Hypertens . 1993;;7:103-104.
40 +
Singh RB, Rastogi SS, Singh NK, Ghosh S, Gupta S, Niaz MA.  Can guava fruit intake decrease blood pressure and blood lipids? J Hum Hypertens . 1993;; 7:33-38.
41 +
Cutler JA, Whelton PK, Appel L, et al.  The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, phase I. JAMA . 1992;;267:1213-1220.
42 +
Bierenbaum ML, Wolf E, Bisgeier G, Maginnis WP.  Dietary calcium: a method of lowering blood pressure. Am J Hypertens . 1988;;1( (suppl) ):149S-152S.
43 +
Sunderrajan S, Bauer JH.  Oral calcium supplementation does not alter blood pressure or vascular response in normotensive men. Circulation . 1984;;70 ( (suppl 2) ):II-130. Abstract 519.
44 +
Zoccali C, Mallamaci F, Delfino D, et al.  Does calcium have a dual effect on arterial pressure? response to 1,25 dihydroxy vitamin D3 and calcium supplements in essential hypertension. J Hypertens . 1987;;5( (suppl 5) ):S267-S269.
45 +
Siani A, Strazzullo P, Guglielmi S, Mancini M.  Clinical studies of the effects of different oral calcium intakes in essential hypertension. J Hypertens . 1987;; 5( (suppl 5) ):S311-S313.
46 +
Orwoll ES, Oviatt S.  Relationship of mineral metabolism and long-term calcium and cholecalciferol supplementation to blood pressure in normotensive men. Am J Clin Nutr . 1990;;52:717-721.
47 +
Rouse IL, Beilin LJ, Mahoney DP, et al.  Nutrient intake, blood pressure, serum and urinary prostaglandins and serum thromboxane B2 in a controlled trial with a lacto-ovo-vegetarian diet. J Hypertens . 1986;;4:241-250.
48 +
Resnick LM, DiFabio B, Marion R, James GD, Laragh JH.  Dietary calcium modifies the pressor effects of dietary salt intake in essential hypertension. J Hypertens . 1986;;4( (suppl 6) ):S679-S681.
49 +
van Beresteyn E, Schaafsma G, de Waard H.  Oral calcium and blood pressure: a controlled intervention trial. Am J Clin Nutr . 1986;;44:883-888.
50 +
Zoccali C, Mallamaci F, Delfino D, et al.  Double-blind randomized, crossover trial of calcium supplementation in essential hypertension. J Hypertens . 1988;;6:451-455.
51 +
Zhou C, Fan S, Zhou L, Ni Y, Huang T, Shi Y.  Clinical observation of treatment of hypertension with calcium. Am J Hypertens . 1994;;7:363-367.
52 +
Hakala P, Karvetti RL.  Weight reduction on lactovegetarian and mixed diets: changes in weight, nutrient intake, skinfold thicknesses and blood pressure. Eur J Clin Nutr . 1989;;43:421-430.
53 +
Takagi Y, Fukase M, Takata S, Fujimi T, Fujita T.  Calcium treatment of essential hypertension in elderly patients evaluated by 24 H monitoring. Am J Hypertens . 1991;;4:836-839.
54 +
Lind L, Wengle B, Wide L, Sorensen OH, Ljunghall S.  Hypertension in primary hyperparathyroidism: reduction of blood pressure by long-term treatment with vitamin D (alphacalcidol): a double-blind, placebo-controlled study. Am J Hypertens . 1988;;1: 397-402.
55 +
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To understand the clinical management of acute heart failure syndromes.
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