This article was downloaded by: [Rutgers University] On: 26 April 2015, At: 18:28 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women a
Susan S. Harris DSc & Bess Dawson-Hughes MD
a
a
Bone Metabolism Laboratory, USDA Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts Published online: 09 Apr 2015.
Click for updates To cite this article: Susan S. Harris DSc & Bess Dawson-Hughes MD (2015): Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women, Journal of the American College of Nutrition, DOI: 10.1080/07315724.2014.959207 To link to this article: http://dx.doi.org/10.1080/07315724.2014.959207
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Original Research
Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women Susan S. Harris, DSc and Bess Dawson-Hughes, MD Bone Metabolism Laboratory, USDA Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
Downloaded by [Rutgers University] at 18:28 26 April 2015
Key words: hydration, calcium supplements, urine calcium concentration, renal stone risk Objective: The aim of this study was to determine whether calcium supplementation, compared with placebo, increases urine calcium concentrations to levels indicative of increased renal stone risk, and the role that fluid intake, as indicated by urine volume, may play in mitigating this risk. Methods: This is a secondary analysis of data from a randomized placebo-controlled trial of 500 mg/d calcium supplementation to prevent bone loss. Subjects were 240 white postmenopausal women age 40 to 70 years in good general health. Effects of supplementation on 1-year changes in 24h urine calcium concentration and urine volume were examined. Results: Both treatment group and urine volume were strong independent predictors of urine calcium concentration (p < 0.001). Among subjects with urine volume under 2 L/24 h, more than half of placebo subjects were at lowest risk for renal stones compared with less than 35% of calcium-supplemented subjects. Among those with higher urine volumes, all placebo subjects and more than 80% of calcium supplemented subjects were at lowest risk. Conclusions: The increased risk of renal stones with calcium supplement use may be largely eliminated with adequate fluid intake, but older adults may not spontaneously consume adequate fluids to minimize this risk and should be counseled to do so.
INTRODUCTION
promoting calcium oxalate crystallization2. In the Nurses’ Health Study I cohort, women with urine calcium concentration of 2.5–3.74 mmol/L had about twice the risk for a first renal stone over the subsequent twelve years compared with women who had concentrations under 2.5 mmol/L, and women with concentrations of 3.75 mmol/L or higher had more than four times the risk [4]. Higher dietary intake has been associated with reduced renal stone risk [7], but the role of calcium supplements in stone formation is controversial. In 1997, Curhan et al. reported a protective association of higher dietary calcium with renal stone risk over 12 years in 97,731 adult women with no history of renal stones [8]. In the same cohort, supplemental calcium from a variety of compounds, in any amount, was observed to increase stone risk by 20%. The authors noted that two-thirds of the women did not consume their supplements with a meal or consumed them with a meal low in oxalates, a
Adequate hydration has many health benefits, including a reduced risk for renal stones [1,2]. Individual fluid requirements vary considerably due to physical and environmental factors, but the Institute of Medicine has designated 2.7 L/d as an adequate fluid intake (AI) for women aged 19 and older [3]. About 20% of total fluid intake comes from food, suggesting that an adequate fluid intake from water and other beverages is just over 2 L/d [1]. This target corresponds well with a reduced risk for renal stones. Women in the large Nurses’ Health Cohort I who had urine volumes of 2 L/24 h or more had less than half the risk for renal stones than women with volumes less than 1.25 L/24h [4]. Inadequate hydration increases renal stone risk by producing urine that is more highly concentrated with solutes including calcium, a component of over 80% of stones [5,6] and by
Address correspondence to: Dr. Susan S. Harris, USDA Jean Mayer HNRCA at Tufts University, 711 Washington St., Boston, MA 02111. E-mail: [email protected].
Journal of the American College of Nutrition, Vol. 0, No. 0, 1–7 (2015) Ó American College of Nutrition/ Published by Taylor & Francis Group, LLC 1
Downloaded by [Rutgers University] at 18:28 26 April 2015
Hydration, Calcium Supplements, and Stone Risk component of most calcium stones. They hypothesized that the difference between dietary and supplemental calcium in this setting may have resulted from higher oxalate binding by dietary calcium. Calcium supplements were also associated with increased risk for renal stones in the Women’s Health Initiative. Specifically, there was a 17% increased risk of renal stones over an average of 7 years of follow-up in 36,282 postmenopausal women with no history of renal stones who were randomized to 1000 mg/d supplemental calcium carbonate and 10 mg/d vitamin D or placebo, taken with meals [9]. In contrast, 2 systematic reviews of multiple calcium supplement trials concluded that calcium supplements were not associated with an increased risk of renal stones [10,11]. One possibility for these discrepant results is that the trials reviewed in these papers were of relatively short duration (generally 1 to 4 years) and recorded very few stone events. It may be that an individual’s risk of developing a stone increases over a longer duration of exposure to calcium supplements, perhaps as a result of varying fluid intakes, changes in body weight, changes in diet, changes in renal function, or variation in other factors that may be needed to complete the causal complement. Urine calcium concentration appears to be a good near-term predicator of the longer term risk for renal stones [4], but the association of calcium supplement use with urine calcium concentration has not been examined in the context of a calcium supplement trial. In this secondary analysis of data from a prior calcium supplementation study to reduce bone loss in postmenopausal women, we examine linkages among calcium supplement use, urine volume as an indicator of fluid intake, and urine calcium concentration as an indicator of renal stone risk. Our objective was to determine whether supplementation increased urine calcium concentrations to levels that have been associated with increased renal stone risk in healthy adults (i.e., 2.5 mmol/L) and the extent to which higher urine volumes may have mitigated any increased risk. This information is relevant for the over 40% of postmenopausal women in the United States who use calcium supplements [12].
METHODS Subjects and Study Design The 240 subjects included in this analysis were participants in a randomized, double-blind, placebo-controlled, 2-year trial of calcium supplementation to prevent bone loss [13]. Three hundred and sixty-one postmenopausal women were enrolled in the study and randomized to placebo or to 500 mg/d elemental calcium as calcium carbonate, or calcium citrate malate. Participants were instructed to maintain their usual diets and to take their study pills at bedtime. Eligibility criteria for the trial included white race, good general health, age 40 to 70 years, at least 6 months since last menses, and dietary calcium intake no
2
greater than 650 mg/d. Exclusion criteria included a history of nontraumatic fracture; renal, hepatic or gastrointestinal disorders associated with abnormal calcium metabolism; a renal stone within the past 5 years; and use of medications known to affect calcium metabolism in the past year. Baseline and 1year measurements were used in this analysis to maximize the sample size. From the 321 subjects who completed the first study year, we excluded those who were missing dietary intake data (n D 1) or 1-year blood measurements (n D 7). We also excluded subjects who appeared to have a sizable under- or overcollection of urine at the baseline or 1-year visit (n D 17). These subjects were identified by a difference between the creatinine content of the baseline and 1-year 24 h urine collections that was more than 2 standard deviations greater than the mean difference for the study group as a whole (3.27 mmol/ 24hr). Finally, we excluded 56 subjects who used diuretics during the study year, resulting in 240 subjects for the analysis (placebo nD79, calcium carbonate nD82, calcium citrate malate nD79). The study was approved by the Institutional Review Board at Tufts University and all subjects provided written informed consent.
Measurements Study visits were conducted at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Massachusetts. Jugs for 24 h urine collections were mailed to study participants before each study visit and brought to the HNRCA on the day of the visit. In keeping with national guidelines as discussed above [3], we classified urine volumes under 2 L/24 h as “low” and volumes of 2 L/24h and higher as “adequate.” Blood was drawn between 7:00 am and 9:30 am after a minimum 8h fast. Twenty-four hour urine calcium was measured by direct-current plasma emission spectroscopy with a Spectrascan 6 (Beckman Instruments, Palo Alto, CA). Relative renal stone risk categories, based on urine calcium concentration, were defined as lowest (
Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women a
Susan S. Harris DSc & Bess Dawson-Hughes MD
a
a
Bone Metabolism Laboratory, USDA Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts Published online: 09 Apr 2015.
Click for updates To cite this article: Susan S. Harris DSc & Bess Dawson-Hughes MD (2015): Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women, Journal of the American College of Nutrition, DOI: 10.1080/07315724.2014.959207 To link to this article: http://dx.doi.org/10.1080/07315724.2014.959207
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Original Research
Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women Susan S. Harris, DSc and Bess Dawson-Hughes, MD Bone Metabolism Laboratory, USDA Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts
Downloaded by [Rutgers University] at 18:28 26 April 2015
Key words: hydration, calcium supplements, urine calcium concentration, renal stone risk Objective: The aim of this study was to determine whether calcium supplementation, compared with placebo, increases urine calcium concentrations to levels indicative of increased renal stone risk, and the role that fluid intake, as indicated by urine volume, may play in mitigating this risk. Methods: This is a secondary analysis of data from a randomized placebo-controlled trial of 500 mg/d calcium supplementation to prevent bone loss. Subjects were 240 white postmenopausal women age 40 to 70 years in good general health. Effects of supplementation on 1-year changes in 24h urine calcium concentration and urine volume were examined. Results: Both treatment group and urine volume were strong independent predictors of urine calcium concentration (p < 0.001). Among subjects with urine volume under 2 L/24 h, more than half of placebo subjects were at lowest risk for renal stones compared with less than 35% of calcium-supplemented subjects. Among those with higher urine volumes, all placebo subjects and more than 80% of calcium supplemented subjects were at lowest risk. Conclusions: The increased risk of renal stones with calcium supplement use may be largely eliminated with adequate fluid intake, but older adults may not spontaneously consume adequate fluids to minimize this risk and should be counseled to do so.
INTRODUCTION
promoting calcium oxalate crystallization2. In the Nurses’ Health Study I cohort, women with urine calcium concentration of 2.5–3.74 mmol/L had about twice the risk for a first renal stone over the subsequent twelve years compared with women who had concentrations under 2.5 mmol/L, and women with concentrations of 3.75 mmol/L or higher had more than four times the risk [4]. Higher dietary intake has been associated with reduced renal stone risk [7], but the role of calcium supplements in stone formation is controversial. In 1997, Curhan et al. reported a protective association of higher dietary calcium with renal stone risk over 12 years in 97,731 adult women with no history of renal stones [8]. In the same cohort, supplemental calcium from a variety of compounds, in any amount, was observed to increase stone risk by 20%. The authors noted that two-thirds of the women did not consume their supplements with a meal or consumed them with a meal low in oxalates, a
Adequate hydration has many health benefits, including a reduced risk for renal stones [1,2]. Individual fluid requirements vary considerably due to physical and environmental factors, but the Institute of Medicine has designated 2.7 L/d as an adequate fluid intake (AI) for women aged 19 and older [3]. About 20% of total fluid intake comes from food, suggesting that an adequate fluid intake from water and other beverages is just over 2 L/d [1]. This target corresponds well with a reduced risk for renal stones. Women in the large Nurses’ Health Cohort I who had urine volumes of 2 L/24 h or more had less than half the risk for renal stones than women with volumes less than 1.25 L/24h [4]. Inadequate hydration increases renal stone risk by producing urine that is more highly concentrated with solutes including calcium, a component of over 80% of stones [5,6] and by
Address correspondence to: Dr. Susan S. Harris, USDA Jean Mayer HNRCA at Tufts University, 711 Washington St., Boston, MA 02111. E-mail: [email protected].
Journal of the American College of Nutrition, Vol. 0, No. 0, 1–7 (2015) Ó American College of Nutrition/ Published by Taylor & Francis Group, LLC 1
Downloaded by [Rutgers University] at 18:28 26 April 2015
Hydration, Calcium Supplements, and Stone Risk component of most calcium stones. They hypothesized that the difference between dietary and supplemental calcium in this setting may have resulted from higher oxalate binding by dietary calcium. Calcium supplements were also associated with increased risk for renal stones in the Women’s Health Initiative. Specifically, there was a 17% increased risk of renal stones over an average of 7 years of follow-up in 36,282 postmenopausal women with no history of renal stones who were randomized to 1000 mg/d supplemental calcium carbonate and 10 mg/d vitamin D or placebo, taken with meals [9]. In contrast, 2 systematic reviews of multiple calcium supplement trials concluded that calcium supplements were not associated with an increased risk of renal stones [10,11]. One possibility for these discrepant results is that the trials reviewed in these papers were of relatively short duration (generally 1 to 4 years) and recorded very few stone events. It may be that an individual’s risk of developing a stone increases over a longer duration of exposure to calcium supplements, perhaps as a result of varying fluid intakes, changes in body weight, changes in diet, changes in renal function, or variation in other factors that may be needed to complete the causal complement. Urine calcium concentration appears to be a good near-term predicator of the longer term risk for renal stones [4], but the association of calcium supplement use with urine calcium concentration has not been examined in the context of a calcium supplement trial. In this secondary analysis of data from a prior calcium supplementation study to reduce bone loss in postmenopausal women, we examine linkages among calcium supplement use, urine volume as an indicator of fluid intake, and urine calcium concentration as an indicator of renal stone risk. Our objective was to determine whether supplementation increased urine calcium concentrations to levels that have been associated with increased renal stone risk in healthy adults (i.e., 2.5 mmol/L) and the extent to which higher urine volumes may have mitigated any increased risk. This information is relevant for the over 40% of postmenopausal women in the United States who use calcium supplements [12].
METHODS Subjects and Study Design The 240 subjects included in this analysis were participants in a randomized, double-blind, placebo-controlled, 2-year trial of calcium supplementation to prevent bone loss [13]. Three hundred and sixty-one postmenopausal women were enrolled in the study and randomized to placebo or to 500 mg/d elemental calcium as calcium carbonate, or calcium citrate malate. Participants were instructed to maintain their usual diets and to take their study pills at bedtime. Eligibility criteria for the trial included white race, good general health, age 40 to 70 years, at least 6 months since last menses, and dietary calcium intake no
2
greater than 650 mg/d. Exclusion criteria included a history of nontraumatic fracture; renal, hepatic or gastrointestinal disorders associated with abnormal calcium metabolism; a renal stone within the past 5 years; and use of medications known to affect calcium metabolism in the past year. Baseline and 1year measurements were used in this analysis to maximize the sample size. From the 321 subjects who completed the first study year, we excluded those who were missing dietary intake data (n D 1) or 1-year blood measurements (n D 7). We also excluded subjects who appeared to have a sizable under- or overcollection of urine at the baseline or 1-year visit (n D 17). These subjects were identified by a difference between the creatinine content of the baseline and 1-year 24 h urine collections that was more than 2 standard deviations greater than the mean difference for the study group as a whole (3.27 mmol/ 24hr). Finally, we excluded 56 subjects who used diuretics during the study year, resulting in 240 subjects for the analysis (placebo nD79, calcium carbonate nD82, calcium citrate malate nD79). The study was approved by the Institutional Review Board at Tufts University and all subjects provided written informed consent.
Measurements Study visits were conducted at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Massachusetts. Jugs for 24 h urine collections were mailed to study participants before each study visit and brought to the HNRCA on the day of the visit. In keeping with national guidelines as discussed above [3], we classified urine volumes under 2 L/24 h as “low” and volumes of 2 L/24h and higher as “adequate.” Blood was drawn between 7:00 am and 9:30 am after a minimum 8h fast. Twenty-four hour urine calcium was measured by direct-current plasma emission spectroscopy with a Spectrascan 6 (Beckman Instruments, Palo Alto, CA). Relative renal stone risk categories, based on urine calcium concentration, were defined as lowest (
