Abstract
Introduction:
Cardiovascular disease is the major cause of mortality in developed countries and has an increasing trend in developing countries. There are some evidences that calcium supplementation may decrease blood pressure and consequently cardiovascular disease, but they are not conclusive and there is no agreement in this respect. The aim of the present study was to assess the effect of supplementary calcium on systolic and diastolic blood pressure in healthy adult women aged 18–30 years.
Materials and Methods:
Seventy-five normotensive volunteers were randomly divided into two groups, the treatment group received 1000 mg/day calcium (four doses of 625 mg calcium carbonate) for 1 month and the control group received placebo (dextrose). Systolic and diastolic blood pressure was determined before and after intervention in supine position after 10 min of rest.
Results:
The mean daily calcium intake from food was 773.9 mg in treatment and 721 mg in control group (no significant difference) but in both the groups dietary calcium intake was less than the recommended dietary allowance: After calcium supplementation, the mean change of systolic blood pressure was not significant in the two groups, but diastolic blood pressure reduced in treatment group and increased in control group (−4.9 vs 2.6 mmHg) (P < 0.05).
Conclusions:
These results suggest that, calcium supplementation does not have any effect on systolic blood pressure of our volunteers but can decrease diastolic blood pressure significantly and therefore it seems that calcium supplementation may be useful for people with increased diastolic blood pressure, especially for those who receive less calcium than recommended dietary allowance.
Keywords: Blood pressure, calcium, Tehran, women
INTRODUCTION
Cardiovascular diseases are the major causes of morbidity and mortality in the world. Undesirable change in blood pressure is also a powerful risk factor for cardiovascular diseases in developed and developing countries such as Iran.[1] The prevalence of hypertension in Iranian adults is more than 20% and it is the main cause of cardiovascular accidents in Iran.[2] It seems that Iranian women are more vulnerable than men.[3] In the past decades there has been a specific attention to dietary habits and hypertension, in this respect many epidemiological studies and clinical trials have been shown the beneficial effects of calcium intake on blood pressure,[4,5,6] but they are not conclusive and there is no agreement in this respect. Wang reported a higher level of blood pressure among women consuming low dietary calcium (<558 mg/day) compared with women with high calcium intake (1,679 mg/day).[7]
However, there are also a lot of findings that indicate no correlation between calcium intake and blood pressure,[8,9,10,11,12,13,14,15,16] even some meta-analyses data indicate about adverse effects,[17,18] on the other hand there are some evidences from observational studies that calcium intake in pregnant women may reduce their offspring blood pressure in future.[19,20] However, later studies did not confirm them.[21] In Iran also some studies have evaluated the effect of calcium on systolic and diastolic blood pressure but the results were not identical.[22,23,24] Insufficient calcium may destabilize cell membranes and consequently more calcium enters in cytosol of muscle cells of arteries and increase contractibility of them which results in hypertension.[25] The effect of calcium on blood pressure is more obvious on population whose calcium intake is low, but in dosages more than 1000 mg per day there was no correlation.[26]
Recent studies showed that calcium sensing receptors affect blood pressure and PTh secretion.[27,28,29] There are evidences that insufficient calcium intake will also increase 1,25(OH)2 D3 and consequently more calcium will enter the smooth muscle cells resulting in increment of blood pressure.[30]
In salt-sensitive people (blood pressure increases with increment of salt intake), there is a close relationship between calcium and sodium excretion and any increase in sodium intake will increase renal calcium excretion, which results in calcium deficiency and subsequently increment in calcitrophic hormones, which ultimately will increase blood pressure. Increasing dietary calcium will attenuate these effects.[31,32,33]
The aim of present study was to assess the effect of supplementary calcium on blood pressure in young healthy adult women.
MATERIALS AND METHODS
Participants
This double-blinded placebo-controlled clinical trial was carried out in normotensive females of Shahid Beheshti University of Medical Sciences in Tehran, Iran. We chose women because they are more vulnerable to hypertension than men,[3] and also were more cooperative, we also chose normotensives because hypertensive individuals were consuming drugs and ethical committee did not allow us to work with them.
The inclusion criteria were body mass index (BMI) <27, age 18–30 years, no known disease, and normal blood pressure. The exclusion criteria were irregular consumption of supplements, no desire for continuation in the project. Participants were not undergoing dietary changes in the last 3 months. Sample size for this study was calculated based on suggested formula for clinical trials:
According to this equation, we reached the sample size of 24 participants for the whole intervention. Because there are high dropouts in clinical trials, we recruited 75 women in this study.
Ethical considerations
The study was approved by Ethical Committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran. All volunteers attended an explanation class and were briefed about the projects and all of them signed the written consent.
Eligible cases were randomly divided into two groups (treatment and control), treatment group received four capsules of supplementary calcium daily, each capsule contained 625 mg calcium carbonate, which is equal to 250 mg of calcium element, placebo group received 1000 mg dextrose capsules instead of calcium carbonate. We advised the volunteers to consume capsules with meals (breakfast, lunch, dinner, and before bed).
We got them capsules weekly and asked them about any inconvenience, any doubt about consumption of capsules made the volunteer to be withdrawn, in this respect more than 15 cases withdrew.
The duration of project was 30 days. Dietary calcium intake was calculated from three days dietary recalls (two working and one off days), dietary recalls was done prior, during, and after intervention. The food analyzing software (N4) of Shahid Beheshti University in Iran was employed for analyzing dietary ingredients. Systolic and diastolic blood pressure was determined before and after intervention in supine position after 10 min of rest.
Statistical methods
Data analysis was performed using SPSS version 18 software (SPSS Inc, Chicago, IL, USA). All subjects who completed the project successfully were included in the final analysis. A paired t-test was used to examine the differences of variables in each group at the beginning and end of the study. Results are described as mean ± standard deviation (mean ± SD). P < 0.05 were considered statistically significant. Dietary records were assessed using nutritionist IV software.
RESULTS
Fifty-three volunteers completed the project successfully; 27 in treatment and 26 in control group. The basal characteristic of participants was as shown in Table 1. There were no significant differences between them with respect to hypertension and other confounding variables such as physical activity, age, weight, and BMI (body mass ndex).
Table 1.
We compared the mean of blood pressure before and after intervention in each group. The results are shown in Tables 2 and 3. No difference was seen.
Table 2.
Table 3.
For more precision, we compared the mean changes in blood pressure in two groups after intervention, now the diastolic blood pressure change in intervention group was different than control group [Table 4].
Table 4.
DISCUSSION
The present double-blinded placebo-controlled clinical trial was carried out in women aged 18–30 years. This study was conducted to investigate the effect of supplementary calcium on blood pressure. The results of the present study indicated that. However our volunteers were educated and they were aware about nutritional needs, but their dietary calcium intake was less than their needs in both the groups [recommended dietary allowance (RDA) for calcium in this age group is equal to 1000 mg calcium per day]. It means that calcium deficiency is a problem in our country. The report of Iran Ministry of Health and Medical Education also confirm our results about calcium deficiency.[34]
In respect to other variables such as BMI, weight, and height our participants were in normal situations.
We add 1000 mg supplementary calcium to normal diet and expected to reduce blood pressure in treatment group, but only diastolic blood pressure was reduced significantly, therefore our results suggest that, calcium supplementation does not have any significant effect on systolic blood pressure of our volunteers but can decrease diastolic blood pressure significantly and therefore it seems that calcium supplementation may be useful for people with increased diastolic pressure, especially those who receive less calcium than the RDA.
Our results [Table 4] showed a mild but nonsignificant reduction in systolic blood pressure in both the groups. This may be attributable to confounding factors. But it was not important in practice.
Ackley and colleagues[35] reported an inverse correlation between calcium intake from dairy products and blood pressure; however, this is partially in accordance to our results, but we should remember that dairy products also contain other bioactive nutrients that may affect blood pressure.
Salem and colleagues[23] reported beneficial effect of supplementary calcium on diastolic and systolic blood pressure. Their results were very similar to ours, but the studied population was different and they studied pregnant women, whereas we investigated normal nonpregnant women.
Park and colleagues[36] also reported an inverse relationship between calcium intake and blood pressure; in their study both systolic and diastolic blood pressure was negatively related to calcium intake. Their population was similar to ours, but the results were not completely similar to our results.
In a recent study in Tehran (Iran), Shidfar et al.[22] reported that supplementary calcium reduced systolic blood pressure but no effect on diastolic blood pressure. Although the amount and form of supplement in this study was very similar to our projects, there was a difference with regard to gender and BMI was completely different, therefore it is not surprising that two studies did not have identical results.
Khatake et al.,[37] has assessed the relationship between serum calcium level, bone mineral density, and blood pressure in postmenopausal women. They did not find any relationship between serum calcium and blood pressure levels. This finding was not similar to ours, but it is not so unexpected because serum calcium level is not an indicative of calcium intake.
CONCLUSIONS
Results of this project showed that calcium intake of almost all of our volunteers was less than the RDA. Although our results showed that calcium supplementation does not have any effect on systolic blood pressure but can decrease diastolic blood pressure significantly and therefore it seems that calcium supplementation may be useful for people with increased diastolic blood pressure, especially those who received less calcium than the RDA. We suggest more studies to be done before using calcium supplements as a treatment for hypertension.
Strengths of the study
This study was done in a population who were calcium deficient, and therefore the effect of calcium supplement should be shown more prominently. Another strength of this study was its double blind nature and homogenicity of intervention and control groups.
Limitations of the study
This study has also some limitations. The study was done on female gender, and a small sample size was recruited. Another limitation was the self-reporting of dietary recalls and no biochemical marker was used. Because of financial limitations and compliance the duration of study was limited to 30 days.
ACKNOWLEDGMENT
The author is grateful to all the participants in the study.
Footnotes
Source of Support: Isfahan University of Medical Sciences
Conflict of Interest: None declared
REFERENCES
- 1.Azizi F, Ghanbarian A, Majidi M, Rahmani M. Distribution of blood pressure and prevalence of hypertension in Tehran adult population: Tehran lipid and glucose study, 1999-2000. J Hum Hypertens. 2002;16:305–12. doi: 10.1038/sj.jhh.1001399. [DOI] [PubMed] [Google Scholar]
- 2.Sarrafzadegan N, Talaei M, Sadeghi M, Kelishadi R, Oveisgharan S, Mohammadifard N, et al. The Isfahan cohort study: Rationale, methods and main findings. J Hum Hypertens. 2011;25:545–53. doi: 10.1038/jhh.2010.99. [DOI] [PubMed] [Google Scholar]
- 3.Malekzadeh MM, Etemadi A, Kamangar F, Khademi H, Golozar A, Islami F, et al. Prevalence, awareness and risk factors of hypertension in a large cohort of Iranian adult population. J Hypertens. 2013;31:1364–71. doi: 10.1097/HJH.0b013e3283613053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Umesawa M, Iso H, Ishihara J, Saito I, Kokubo Y, Inoue M, et al. Dietary calcium intake and risks of stroke, its subtypes and coronary heart disease in Japanese: The JPHC Study Cohort I. Stroke. 2008;39:2449–56. doi: 10.1161/STROKEAHA.107.512236. [DOI] [PubMed] [Google Scholar]
- 5.Iso H, Stampfer MJ, Manson JE, Rexrode K, Hennekens CH, Colditz JA, et al. Prospective study of calcium, potassium and magnesium intake and risk of stroke in women. Stroke. 1999;30:1772–9. doi: 10.1161/01.str.30.9.1772. [DOI] [PubMed] [Google Scholar]
- 6.Abbott RD, Curb JD, Rodriguez BL, Sharp DS, Burchfiel CM, Yano K. Effect of dietary calcium and milk consumption on risk of thromboembolic stroke in older middle-aged men. The Honolulu Heart Program. Stroke. 1996;27:813–8. doi: 10.1161/01.str.27.5.813. [DOI] [PubMed] [Google Scholar]
- 7.Wang L, Manson JE, Buring JE, Lee IM, Sesso HD. Dietary intake of dairy products, calcium, and vitamin D and the risk of hypertension in middle-aged and older women. Hypertension. 2008;5:1073–9. doi: 10.1161/HYPERTENSIONAHA.107.107821. [DOI] [PubMed] [Google Scholar]
- 8.Khatake PD, Jadhav SS, Afroz S. Relation between Serum Calcium Level, Bone mineral density and blood pressure in postmenopausal women. Int J Recent Trends Sci Tech. 2013;7:86–8. [Google Scholar]
- 9.Al-Delaimy WK, Rimm E, Willett WC, Stampfer MJ, Hu FB. A prospective study of calcium intake from diet and supplements and risk of ischemic heart disease among men. Am J Clin Nutr. 2003;77:814–8. doi: 10.1093/ajcn/77.4.814. [DOI] [PubMed] [Google Scholar]
- 10.Marniemi J, Alanen E, Impivaara O, Seppänen R, Hakala P, Rajala T, et al. Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutr Metab Cardiovasc Dis. 2005;15:188–97. doi: 10.1016/j.numecd.2005.01.001. [DOI] [PubMed] [Google Scholar]
- 11.Ascherio A, Rimm EB, Hernan MA, Giovannucci EL, Kawachi I, Stampfer MJ, et al. Intake of potassium, magnesium, calcium and fiber and risk of stroke among US men. Circulation. 1998;98:1198–204. doi: 10.1161/01.cir.98.12.1198. [DOI] [PubMed] [Google Scholar]
- 12.Larsson SC, Virtanen MJ, Mars M, Männistö S, Pietinen P, Albanes D, et al. Magnesium, calcium, potassium and sodium intakes and risk of stroke in male smokers. Arch Intern Med. 2008;168:459–65. doi: 10.1001/archinte.168.5.459. [DOI] [PubMed] [Google Scholar]
- 13.Umesawa M, Iso H, Date C, Yamamoto A, Toyoshima H, Watanabe Y, et al. Dietary intake of calcium in relation to mortality from cardiovascular disease: The JACC Study. Stroke. 2006;37:20–6. doi: 10.1161/01.STR.0000195155.21143.38. [DOI] [PubMed] [Google Scholar]
- 14.Ross RK, Yuan JM, Henderson BE, Park J, Gao YT, Yu MC. Prospective evaluation of dietary and other predictors of fatal stroke in Shanghai, China. Circulation. 1997;96:50–5. doi: 10.1161/01.cir.96.1.50. [DOI] [PubMed] [Google Scholar]
- 15.Van der Vijver LP, van der Waal MA, Weterings KG, Dekker JM, Schouten EG, Kok FJ. Calcium intake and 28-year cardiovascular and coronary heart disease mortality in Dutch civil servants. Int J Epidemiol. 1992;21:36–9. doi: 10.1093/ije/21.1.36. [DOI] [PubMed] [Google Scholar]
- 16.Larsson SC, Virtamo J, Wolk A. Potassium, calcium and magnesium intakes and risk of stroke in women. Am J Epidemiol. 2011;174:35–43. doi: 10.1093/aje/kwr051. [DOI] [PubMed] [Google Scholar]
- 17.Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: A reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011;94:1144–9. doi: 10.3945/ajcn.111.015032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: Meta-analysis. BMJ. 2010;341:c3691. doi: 10.1136/bmj.c3691. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.McGarvey ST, Zinner SH, Willett WC, Rosner B. Maternal prenatal dietary potassium, calcium, magnesium, and infant blood pressure. Hypertension. 1991;17:218–24. doi: 10.1161/01.hyp.17.2.218. [DOI] [PubMed] [Google Scholar]
- 20.Gillman MW, Rifas-Shiman SL, Kleinman KP, Rich-Edwards JW, Lipshultz SE. Maternal calcium intake and offspring blood pressure. Circulation. 2004;110:1990–5. doi: 10.1161/01.CIR.0000143199.93495.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Hawkesworth S, Sawo Y, Fulford AJ, Goldberg GR, Jarjou LM, Prentice A, et al. Effect of maternal calcium supplementation on offspring blood pressure in 5- to 10-y-old rural Gambian children. Am J Clin Nutr. 2010;92:741–7. doi: 10.3945/ajcn.2010.29475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Shidfar F, Moghayedi M, Reza S, Kerman J, Hosseini S, Shidfar S. Effects of a calcium supplement on serum lipoproteins, polipoprotein B, and blood pressure in overweight men. Int J Endocrinol Metab. 2010;8:194–200. [Google Scholar]
- 23.Salem Z, Omidvar N, Mahmudi M, Ovladi B. The effects of supplementary calcium on blood pressure of pregnant women. Journal of Shahid Beheshti University of Medical Sciences Research. 2000;24:95–103. [Google Scholar]
- 24.Ostadrahimi AR, Mahboob S, Afiatmilani SH. Relationship between blood pressure and daily sodium, potassium, calcium intake and BMI. J Qazvin Univ Med Sci. 2003;26:36–40. [Google Scholar]
- 25.Houston MC, Harper KJ. Potassium, Magnesium, and Calcium: Their Role in Both the Cause and Treatment of Hypertension. J Clin Hypertens. 2008;10(Suppl 2):3–11. doi: 10.1111/j.1751-7176.2008.08575.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et al. A clinical trial of the effects of dietary patterns on blood pressure. Research Group. N Engl J Med. 2004;336:1117–24. doi: 10.1056/NEJM199704173361601. [DOI] [PubMed] [Google Scholar]
- 27.Jorde R, Sundsfjord J, Haug E, Bonaa KH. Relation between low calcium intake, parathyroid hormone, and blood pressure. Hypertension. 2000;35:1154–9. doi: 10.1161/01.hyp.35.5.1154. [DOI] [PubMed] [Google Scholar]
- 28.Smajilovic S, Tfelt-Hansen J. Novel role of the calcium-sensing receptor in blood pressure modulation. Hypertension. 2008;52:994–1000. doi: 10.1161/HYPERTENSIONAHA.108.117689. [DOI] [PubMed] [Google Scholar]
- 29.Tfelt-Hansen J, Brown EM. The calcium-sensing receptor in normal physiology and pathophysiology: A review. Crit Rev Clin Lab Sci. 2005;42:35–70. doi: 10.1080/10408360590886606. [DOI] [PubMed] [Google Scholar]
- 30.Resnick L. The cellular ionic basis of hypertension and allied clinical conditions. Progr Cardiovasc Dis. 2005;42:1–22. doi: 10.1016/s0033-0620(99)70006-x. [DOI] [PubMed] [Google Scholar]
- 31.Yoon JS, Lee MJ. Calcium Status and Bone Mineral Density by the Level of Sodium Intake in Young Women. Korean J Community Nutr. 2013;18:125–33. [Google Scholar]
- 32.Zemel MB, Gualdoni SM, Sowers JR. Reductions in total and extracellular water associated with calcium-induced natriuresis and the antihypertensive effect of calcium in blacks. Am J Hypertens. 1988;1:70–2. doi: 10.1093/ajh/1.1.70. [DOI] [PubMed] [Google Scholar]
- 33.Zemel MB, Kraniak J, Standley PR, Sowers JR. Erythrocyte cation metabolism in salt-sensitive blacks as affected by dietary sodium and calcium. Am J Hypertens. 1988;1:386–92. doi: 10.1093/ajh/1.4.386. [DOI] [PubMed] [Google Scholar]
- 34.Sheikholeslam R. 1st ed. Iran: Ministry of Health and medical education; 2007. Micronutrients and methods to prevent their deficiencies based on based on food supplementation. [Google Scholar]
- 35.Ackley S, Connor EB, Suarez L. Dairy products, calcium, and blood pressure. Am J Clin Nutr. 1983;38:457–61. doi: 10.1093/ajcn/38.3.457. [DOI] [PubMed] [Google Scholar]
- 36.Park J, Lee GS, Kim J. Relationship between dietary sodium, potassium, and calcium, anthropometric indexes, and blood pressure in young and middle aged Korean adults. Nutr Res Pract. 2010;4:155–62. doi: 10.4162/nrp.2010.4.2.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Khatake PD, Jadhav SS, Afroz S. Relation between Serum Calcium Level, Bone Mineral Density and Blood Pressure in Postmenopausal Women. Int J Recent Trends Sci Tech. 2013;7:86–8. [Google Scholar]