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Calcium intake: covariates and confounders
One common nutrient postulated to be protective against osteoporosis, hypertension, and colon cancer is dietary calcium. We report here nutrient patterns by calcium intake in older adult residents of a geographically defined community in Southern California. The analysis included all 426 men and 531 women aged 50-79 y with complete 24-h diet data. Nutrient-density-adjusted calcium intake was divided into tertiles: low intake (less than 284 mg/1000 kcal), mid intake (284-440 mg/1000 kcal), and high intake (greater than 440 mg/1000 kcal). The distribution of the reported 24-h nutrient density of protein, fat, fiber, caffeine, trace minerals, vitamin D, and vitamin C was examined in relation to the calcium-intake tertiles. In both men and women, the adjusted intakes of protein, saturated fatty acids, vitamin D, magnesium, and phosphorus were significantly higher in the high-calcium-intake group than in the low- and mid-calcium-intake groups. In both men and women, alcohol intake was significantly lower in the high-calcium-intake group. Studies postulating a protective role for calcium will need to consider the multicolinearity in the Western diet.
Am-J-Clin-Nutr. 1991 Mar; 53(3): 741-4
Relationship between vitamin and calcium supplement use and colon cancer
The relationship between vitamin supplement use and colon cancer was assessed in a population-based case-control study among men and women aged 30-62 years. Cases were 251 men and 193 women diagnosed with colon cancer in 1985-1989 in three counties in the Seattle metropolitan area who were identified from the Surveillance, Epidemiology, and End Results cancer registry. Controls were 233 men and 194 women identified by random digit dialing. Supplement use was assessed by questions on frequency, duration, and dose per day (for individual supplements) or type (for multivitamins) during the 10-year period ending 2 years before diagnosis. All results were adjusted for age and sex and were not confounded by other measured behaviors. The average daily intake of supplemental vitamins A, C, E, folic acid, calcium, and multivitamins during the reference period were each associated with reduced risk of colon cancer (all P for trend < 0.03). The strongest associations were for use of vitamin E (odds ratio, 0.43; 95% confidence interval, 0.26-0.71 for > or = 200 IU/day versus none) and multivitamins (odds ratio, 0.49; 95% confidence interval, 0.35-0.69 for daily use versus no use; both P for trend < 0.001). These two associations were also significant using a stricter test of trend limited to supplement users, which reduces the effect of colinearity among these exposures. Because almost all vitamin D supplementation comes from multivitamin pills, the association of vitamin D use with colon cancer could not be distinguished from that of multivitamin use. Clinical trials or cohort studies with long-term assessment would be needed before public health recommendations could be made about supplement use.
White-E; Shannon-JS; Patterson-RE
Cancer-Epidemiol-Biomarkers-Prev. 1997 Oct; 6(10): 769-74
Pharmacologic prevention of colonic neoplasms. Effects of calcium, vitamins, omega fatty acids, and nonsteroidal anti-inflammatory drugs
Dietary supplements of calcium, vitamins A, C, and E, carotenoids, and omega-3 fatty acids can reduce the yield of experimental cancers in animals and reverse the pattern of abnormal epithelial proliferation in animals and humans. Epidemiological studies indicate that diets containing high amounts of these agents convey a protective effect against the development of colon cancer. Moreover, regular aspirin use in humans appears to reduce the risk of colon cancer and sulindac causes regression of polyps in patients with familial polyposis. These agents are promising for the prevention of human colorectal cancer, but their efficacy has not yet been shown in prospective, controlled trials. Thus, although it is tempting to speculate that in the future we may treat our patients who have a predisposition to colon polyps and cancer, or even healthy people at average risk, with such ordinary supplements as calcium, vitamins, fish oil, or aspirin, such advice at this time is premature.
Dig-Dis. 1996 Mar-Apr; 14(2): 119-28
Calcium supplementation modifies the relative amounts of bile acids in bile and affects key aspects of human colon physiology
Use of calcium supplements has increased dramatically in recent years yet little is known about the effect of calcium supplementation on colon physiology. We supplemented 22 individuals with a history of resected adenocarcinoma of the colon, but currently free of cancer, with 2000 or 3000 mg calcium for 16 wk. The effects of supplementation on duodenal bile acids and important fecal characteristics including total fecal output, wet and dry weight, pH, bile acids (in solids and in fecal water), and concentrations and total excretion of calcium, magnesium, phosphates (organic and inorganic), unesterified fatty acids and total fat were determined. Calcium supplementation significantly decreased the proportion of water in the stool (P = 0.03), doubled fecal excretion of calcium (P = 0.006), and increased excretion of organic phosphate (P = 0.035) but not magnesium. Calcium supplementation significantly decreased the proportion of chenodeoxycholic acid in bile (P = 0.007) and decreased the ratio of lithocholate to deoxycholate in feces (P = 0.06). The concentration of primary bile acids in fecal water decreased after 16 wk Ca supplementation. Together with other reports of a "healthier" bile acid profile with respect to colon cancer when changes such as those observed in this study were achieved, these results suggest a protective effect of calcium supplementation against this disease.
Lupton-JR; Steinbach-G; Chang-WC; O'Brien-BC; Wiese-S; Stoltzfus-CL; Glober-GA; Wargovich-MJ; McPherson-RS; Winn-RJ
J-Nutr. 1996 May; 126(5): 1421-8
Randomized, double-blinded, placebo-controlled study of effect of wheat bran fiber and calcium on fecal bile acids in patients with resected adenomatous colon polyps
BACKGROUND: Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. PURPOSE: We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. METHODS: In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. RESULTS: All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. CONCLUSIONS: High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. IMPLICATION: Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.
Alberts-DS; Ritenbaugh-C; Story-JA; Aickin-M; Rees-McGee-S; Buller-MK; Atwood-J; Phelps-J; Ramanujam-PS; Bellapravalu-S; Patel-J; Bextinger-L; Clark-L
J-Natl-Cancer-Inst. 1996 Jan 17; 88(2): 81-92
Calcium is necessary for the prevention and treatment of diseases such as osteoporosis, hypertension, and, possibly, colon cancer. Supplementation is useful when dietary calcium intake is low, as is the current situation in North America. There are many factors to consider before recommending any one form of supplement. A consideration for calcium carbonate tablets is whether the tablet disintegrates and whether or not a lack of food or acid in the stomach will hinder utilization. Other forms of calcium, particularly the chelated calcium salts, are better absorbed in fasting achlorhydric subjects but have less calcium per gram of supplement. Interaction of calcium with other mineral nutrients and the presence of contaminating metals has focused attention on safety. Based on present evidence, chelated calcium and refined calcium carbonate tablets (including those labeled as antacids) may be safely and effectively ingested by most people at doses generally recommended for treatment or prevention of osteoporosis. One should not exceed 2,000 mg of calcium, except at the advice of their health care provider, as inadvertent mineral deficiencies may arise. Persons at risk for developing milk-alkali syndrome, such as thiazide users and persons with renal failure, should be identified and monitored for alkalosis and hypercalcemia when using calcium supplements.
Whiting-SJ; Wood-R; Kim-K
J-Am-Acad-Nurse-Pract. 1997 Apr; 9(4): 187-92
Calcium supplementation and prevention of pregnancy induced hypertension
In a randomized controlled trial 201 healthy nulliparous women were randomly allocated by means of a computer generated randomization list. From 20 weeks of gestation until delivery they received either 2 g of oral elemental calcium (n = 103) per day or an identical placebo (n = 98). Eleven women (5.47%) were lost to follow-up after randomization. The study groups were very similar at the time of randomization; with respect to several clinical and demographic variables. Treatment compliance was very similar in both groups as was determined by pill count. The rate of pregnancy induced hypertension was lower in the calcium group than in the placebo group 8.24%; vs 29.03%; (RR = 0.28; 95% CI 0.14-0.59). The incidence of gestational hypertension was 6.18% in the calcium group and 17.20% in the placebo group (RR = 0.28; 95% CI 0.08-0.80), and the incidence of preeclampsia was 2.06% in the calcium group and 11.82% in the placebo group (RR = 0.13; 95% CI 0.01-0.64). In conclusion calcium supplementation given in pregnancy to nulliparous women reduces the incidence of pregnancy induced hypertension.
Purwar-M; Kulkarni-H; Motghare-V; Dhole-S
J-Obstet-Gynaecol-Res. 1996 Oct; 22(5): 425-30
Reversal of hypertension and endothelial dysfunction in deoxycorticosterone-NaCl-treated rats by high-Ca2+ diet
We tested the effect of high-Ca2+ diet on blood pressure and responses of mesenteric arterial rings in vitro in established deoxycorticosterone (DOC)-NaCl hypertension. Ca2+ supplementation (2.5%) of Wistar rats, which was commenced 8 wk after initiation of DOC-NaCl treatment (Ca(2+)-DOC group), reversed the development of hypertension, whereas in animals ingesting a normal diet (1.1% Ca2+; DOC group) blood pressure continued to rise until the end of the 12-wk study. In norepinephrine-precontracted arterial rings, relaxations to acetylcholine (ACh) and sodium nitroprusside were attenuated in the DOC group, but these responses were significantly improved by Ca2+ supplementation. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester, in the presence of diclofenac, totally abolished ACh-induced relaxations in the DOC group but only attenuated them in the Ca(2+)-DOC group. The remaining relaxation was further inhibited by apamin, an inhibitor of Ca(2+)-activated K+ channels, and practically abolished after blockade of ATP-dependent K+ channels by glyburide. Interestingly, when endothelium-dependent hyperpolarization was prevented using precontractions induced by KCl, no differences were found in relaxations to ACh between the groups. In conclusion, high-Ca(2+) diet effectively reduced blood pressure in DOC-NaCl hypertension and concomitantly enhanced arterial relaxation. Because the relaxations to ACh in the Ca(2+)-DOC group were augmented in the absence and presence of NO synthesis inhibition but not under conditions of prevented hyperpolarization, these enhanced relaxations could be attributed to promoted endothelium-dependent hyperpolarization in the Ca(2+)-supplemented animals.
Makynen-H; Kahonen-M; Wu-X; Wuorela-H; Porsti-I
Am-J-Physiol. 1996 Apr; 270(4 Pt 2): p250-7
High calcium diet reduces blood pressure in exercised and nonexercised hypertensive rats
The effects of long-term high calcium diet and physical exercise and their combined effects on the development of hypertension, plasma and tissue atrial natriuretic peptide, and arterial function were studied in spontaneously hypertensive rats with Wistar-Kyoto rats serving as normotensive controls. Hypertensive rats were made to exercise by running on a treadmill up to 900 m/day. Calcium supplementation was instituted by increasing the calcium content of the chow from 1.1% to 2.5%. During the 23-week study, calcium supplementation attenuated the rise in blood pressure in both trained and nontrained hypertensive animals, whereas exercise training had no significant effect on blood pressure. The high calcium diet alone was associated with reduced plasma and ventricular tissue contents of atrial natriuretic peptide, both of which were increased by exercise. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Neither increased dietary calcium nor endurance training affected the contractile sensitivity of endothelium-intact preparations to potassium chloride or norepinephrine. However, a high calcium diet enhanced the arterial relaxation induced by the return of potassium to the organ bath upon precontraction with potassium-free solution, and also moderately augmented relaxations to acetylcholine, sodium nitrite, and isoproterenol. Exercise training did not affect the potassium relaxation rate, but enhanced responses to acetylcholine, isoproterenol, and sodium nitrite. In conclusion, enhanced arterial potassium relaxation, a response reflecting the function of the vascular sodium pump, paralleled well the long-term blood pressure lowering action of increased dietary calcium intake in exercised and nonexercised hypertensive rats. However, augmented arterial relaxation to agonists could also be observed in the absence of reduced blood pressure following regular physical exercise.
Sallinen-K; Arvola-P; Wuorela-H; Ruskoaho-H; Vapaatalo-H; Porsti-I
Am-J-Hypertens. 1996 Feb; 9(2): 144-56
Cardiovascular effect of oral calcium supplementation: echocardiographic study in patients with essential hypertension
Oral calcium (Ca) supplementation mildly reduces blood pressure. The authors studied the effects of Ca supplementation on the cardiovascular system in patients with mild to moderate essential hypertension. Twelve patients aged forty-nine to seventy years (7 men and 5 women, mean age with 60.3 +/- 7.2 years) participated. The investigators orally administered Ca (1.0 g/day for one week) under hospitalization, adding to a dietary intake of Ca (0.6 g/day). Left ventricular function and systemic arterial compliance were evaluated by M-mode and pulsed Doppler echocardiographies before and after seven days of Ca supplementation. Left ventricular contractility and afterload were not changed. Preload indicated by end-diastolic volume was significantly decreased after Ca supplementation (109.6 +/- 8.5 vs 107.3 +/- 8.2 mL, P < 0.05). Myocardial relaxation evaluated by IIa-mitral valve opening time (87.7 +/- 6.7 vs 82.1 +/- 6.2 ms, P < 0.01) and maximum descending rate of the left ventricular posterior wall (10.6 +/- 1.0 vs 12.4 +/- 1.0 cm/s, P < 0.01), and atrioventricular net compliance assessed by the descending slope of rapid filling flow in the left ventricular inflow tract (2.63 +/- 0.24 vs 2.26 +/- 0.17 m/s2, P <0.05), as well as systemic arterial compliance (2.05 +/- 0.20 vs 2.73 +/- 0.26 mL/mmHg, P < 0.01) were significantly improved by Ca supplementation. Oral Ca supplementation improved the disturbed left ventricular diastolic function and systemic arterial compliance.
Dazai-Y; Kohara-K; Iwata-T; Sumimoto-T; Hiwada-K
Angiology. 1996 Mar; 47(3): 273-80
Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials
OBJECTIVE: To review the effect of calcium supplementation during pregnancy on blood pressure, preeclampsia, and adverse outcomes of pregnancy. 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: Fourteen randomized trials involving 2459 women were eligible. DATA EXTRACTION: Reviewers working independently in pairs abstracted data and assessed validity according to six quality criteria. DATA SYNTHESIS: Each trial yielded differences in blood pressure change between calcium supplementation and control groups that we weighted by the inverse of the variance. The pooled analysis showed a reduction in systolic blood pressure of -5.40 mm Hg (95% confidence interval [CI], -7.81 to -3.00 mm Hg; P<.001) and in diastolic blood pressure of -3.44 mm Hg (95% CI, -5.20 to -1.68 mm Hg; P<.001). The odds ratio for preeclampsia in women with calcium supplementation compared with placebo was 0.38 (95% CI, 0.22 to 0.65). CONCLUSIONS: Calcium supplementation during pregnancy leads to an important reduction in systolic and diastolic blood pressure and preeclampsia. While pregnant women at risk of preeclampsia should consider taking calcium, many more patient events are needed to confirm calcium's impact on maternal and fetal morbidity.
Bucher-HC; Guyatt-GH; Cook-RJ; Hatala-R; Cook-DJ; Lang-JD; Hunt-D
JAMA. 1996 Apr 10; 275(14): 1113-7
Effects of dietary calcium supplementation on blood pressure. A meta-analysis of randomized controlled trials
OBJECTIVE: To review the effect of supplemental calcium on blood pressure. DATA SOURCE: We searched MEDLINE and EMBASE for 1996 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.
Bucher-HC; Cook-RJ; Guyatt-GH; Lang-JD; Cook-DJ; Hatala-R; Hunt-DL
JAMA. 1996 Apr 3; 275(13): 1016-22
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