Editorial See corresponding article on page 1023.
Serum calcium and its complex association with incident type 2 diabetes1 Ranee Chatterjee and Pao-Hwa Lin* Department of Medicine, Duke University School of Medicine, Durham, NC
Type 2 diabetes is a worldwide epidemic that disparately affects certain populations. Obesity is a leading risk factor for type 2 diabetes and has been the main focus for preventive efforts. However, obesity continues to be a serious health issue in the United States, and preventive efforts have not been fruitful. In addition to obesity, other risk factors, such as the one suggested by Rooney et al. (1) in this issue of the Journal, imply opportunities for the development of new prevention strategies. In this study, the investigators evaluated serum calcium as a potential risk factor for incident diabetes in a large biracial prospective cohort from the ARIC (Atherosclerosis Risk in Communities) study. They also evaluated possible racial differences in the association between serum calcium and diabetes risk. Serum calcium is a vital mineral for many cellular processes that is tightly regulated by 3 main mechanisms, including renal filtering and reabsorption of calcium, bone turnover, and intestinal absorption of dietary calcium (diet or supplements) (2). In turn, these mechanisms are regulated by several endogenous factors, including parathyroid hormone, parathyroid hormone–related peptide, vitamin D, ionized calcium, and receptors for these factors, and renal function (2). Serum calcium, as well as each of these other endogenous factors, has been associated with altered glucose metabolism—which affects b cell function or insulin sensitivity—and for some, with even longer-term diabetes risk (3–8). Although the exact mechanism by which serum calcium may relate to diabetes risk is unclear, earlier studies suggested that one possible mechanism is that higher intracellular calcium may decrease the effect of insulin in adipocytes by reducing glucose transporters, in particular the glucose transporter type 4 (GLUT4) and insulin receptor activity (9, 10). In the study by Rooney et al. (1) the investigators found that, compared with those in the lowest quintile of serum calcium concentrations, participants in the highest quintile had a higher risk of diabetes. Such an association was not greatly influenced after adjustment for certain endogenous factors that may influence serum calcium, such as serum parathyroid hormone, vitamin D, and phosphorus. In addition, despite the lack of a significant racial interaction, the positive association between serum calcium and diabetes risk was stronger in African Americans than in whites. Neither the calcium-sensing receptor polymorphisms nor renal function was found to be a significant effect modifier on the association.
In addition to endogenous regulators, exogenous factors may affect serum calcium. The investigators addressed one such common exogenous influence, which is diuretic use. Different types of diuretics affect serum calcium in different ways. Loop diuretics, such as furosemide, increase urinary calcium excretion and can lower serum calcium; thiazide diuretics, which are considered first-line therapy for hypertension (11), decrease urinary calcium excretion and can lead to higher serum calcium concentrations; amiloride, a potassium-sparing diuretic, also leads to a decrease in urinary calcium excretion (12). In this study, although the association persisted after the exclusion of participants taking any diuretic, there was a decrease in the magnitude of the association between serum calcium and diabetes risk. Further study is warranted to determine the prevalence of each type of diuretic use and its respective influence on serum calcium concentrations itself as well as on the association between serum calcium and diabetes risk. Dietary calcium intake is another important exogenous factor for the maintenance of bone and body stores of calcium as well as for serum calcium concentrations; however, when dietary calcium intakes are low, endogenous hormonal factors, especially parathyroid hormone and vitamin D metabolites, act quickly to maintain physiologically viable concentrations of serum calcium (13). Therefore, with this interplay of factors, dietary calcium intake and serum calcium concentrations are not usually observed to correlate tightly. However, the excessive intake of calcium supplements can increase serum calcium concentrations, and a low dietary calcium intake may contribute to lower serum calcium concentrations (13). Unlike the positive association found between serum calcium and diabetes risk, results from observational studies have shown that dietary calcium intake is inversely associated with diabetes risk. The primary source of dietary calcium is from dairy foods and to a lesser extent from certain vegetables and calcium-fortified foods. A higher intake of dairy foods overall has been associated with a lower risk of type 2 diabetes (14, 15); but some studies found that the intake of only certain types of dairy foods, particularly yogurt, is associated with a lower risk of diabetes (15, 16). Some evidence 1
RC was supported by NIH/Duke Clinical and Translational Science award KL2TR001115-02. *To whom correspondence should be addressed. E-mail: pao.hwa.lin@ dm.duke.edu. First published online September 14, 2016; doi: 10.3945/ajcn.116.143321.
Am J Clin Nutr 2016;104:957–8. Printed in USA. Ó 2016 American Society for Nutrition
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also suggests that dietary calcium from foods compared with calcium supplements may have differing health benefits; therefore, possible differences in impact on diabetes risk should be investigated (17). The influence of dietary calcium from food and supplements on serum calcium concentrations or on diabetes risk was not addressed in this study. Mechanisms linking dietary calcium or dairy intake and serum calcium to diabetes risk may differ. In the United States, African Americans have a 75% higher prevalence of diabetes compared with whites (18). Although traditional risk factors such as obesity may account for a large proportion of the racial disparity in diabetes risk, they do not account for all of the disparity (19). Rooney et al. examined possible racial differences in the association between serum calcium and diabetes risk. Although they did not find a significant racial interaction, the magnitude of the association was stronger in African Americans than in whites. As described in this study, there are known racial differences in factors that contribute to serum calcium homeostasis that could explain this finding, including racial differences in the endogenous factors that regulate serum calcium, such as renal function, vitamin D, and parathyroid hormone (20–23). In addition, there are racial differences in exogenous contributors to serum calcium concentrations. For the treatment of hypertension, African Americans have been found to be more responsive to thiazide diuretics, and for this group, thiazides are recommended more strongly as a first-line agent for treatment and are used more than for whites (24). The use of thiazides could, in part, explain the higher serum calcium concentrations found in this cohort of African-American participants and should be investigated as a possible confounder of the calcium-diabetes association, particularly among African Americans. There may also be a racial-ethnic disparity in dietary calcium intake from dairy foods. African Americans commonly consume fewer dairy foods than do whites, in part due to either perceived or actual concerns with lactose tolerance (25, 26). The finding that serum calcium concentrations were higher in African Americans than in whites suggests a mechanism that is less likely to be related to dietary intake of calcium. The finding that higher serum calcium is associated with increased diabetes risk is important and needs to be investigated further. As with other risk factors for diabetes, the association between serum calcium and diabetes risk is complex. Further research and understanding of the mechanisms underlying the association between serum calcium and diabetes risk may provide a new opportunity to combat the diabetes epidemic. RC drafted the manuscript, and P-HL critically reviewed and edited the manuscript. Neither of the authors had a conflict of interest to report.
REFERENCES 1. Rooney MR, Pankow JS, Sibley SD, Selvin E, Reis JP, Michos ED, Lutsey PL. Serum calcium and incident type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 2016;104: 1023–9. 2. Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol 2010;5(Suppl 1):S23–30. 3. Kramer CK, Swaminathan B, Hanley AJ, Connelly PW, Sermer M, Zinman B, Retnakaran R. Prospective associations of vitamin D status with beta-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status. Diabetes 2014;63:3868–79. 4. Squires PE, Jones PM, Younis MY, Hills CE. The calcium-sensing receptor and beta-cell function. Vitam Horm 2014;95:249–67.
5. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 2013;36:1422–8. 6. Chang-Chen KJ, Mullur R, Bernal-Mizrachi E. Beta-cell failure as a complication of diabetes. Rev Endocr Metab Disord 2008;9:329–43. 7. Wareham NJ, Byrne CD, Carr C, Day NE, Boucher BJ, Hales CN. Glucose intolerance is associated with altered calcium homeostasis: a possible link between increased serum calcium concentration and cardiovascular disease mortality. Metabolism 1997;46:1171–7. 8. Sun G, Vasdev S, Martin GR, Gadag V, Zhang H. Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population. Diabetes 2005;54:3336–9. 9. Byyny RL, LoVerde M, Lloyd S, Mitchell W, Draznin B. Cytosolic calcium and insulin resistance in elderly patients with essential hypertension. Am J Hypertens 1992;5:459–64. 10. Begum N, Leitner W, Reusch JE, Sussman KE, Draznin B. GLUT-4 phosphorylation and its intrinsic activity: mechanism of Ca(21)-induced inhibition of insulin-stimulated glucose transport. J Biol Chem 1993;268:3352–6. 11. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20. 12. Haas M. The Na-K-Cl cotransporters. Am J Physiol 1994;267:C869–85. 13. Institute of Medicine. Dietary Reference Intakes for calcium and vitamin D. Washington (DC): National Academies Press; 2011. 14. Elwood PC, Pickering JE, Givens DI, Gallacher JE. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids 2010;45:925–39. 15. Tong X, Dong JY, Wu ZW, Li W, Qin LQ. Dairy consumption and risk of type 2 diabetes mellitus: a meta-analysis of cohort studies. Eur J Clin Nutr 2011;65:1027–31. 16. Forouhi NG. Association between consumption of dairy products and incident type 2 diabetes—insights from the European Prospective Investigation into Cancer Study. Nutr Rev 2015;73(Suppl 1):15–22. 17. Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP Diet and Health Study. JAMA Intern Med 2013;173:639–46. 18. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014 [cited 2016 Aug 23]. Available from: https://www.cdc.gov/ diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. 19. Chatterjee R, Brancati FL, Shafi T, Edelman D, Pankow JS, Mosley TH, Selvin E, Yeh HC. Non-traditional risk factors are important contributors to the racial disparity in diabetes risk: the Atherosclerosis Risk in Communities Study. J Gen Intern Med 2014;29:290–7. 20. Guti´errez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011;22:1745–53. 21. Guti´errez OM, Parsa A, Isakova T, Scialla JJ, Chen J, Flack JM, Nessel LC, Gupta J, Bellovich KA, Steigerwalt S, et al. Genetic African ancestry and markers of mineral metabolism in CKD. Clin J Am Soc Nephrol 2016;11:653–62. 22. Palmer Alves T, Lewis J. Racial differences in chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States: a social and economic dilemma. Clin Nephrol 2010;74(Suppl 1):S72–7. 23. Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, Haigh PI, Adams AL. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013;98:1122–9. 24. Flack JM, Sica DA, Bakris G, Brown AL, Ferdinand KC, Grimm RH Jr., Hall WD, Jones WE, Kountz DS, Lea JP, et al. Management of high blood pressure in blacks: an update of the International Society on Hypertension in Blacks consensus statement. Hypertension 2010;56:780–800. 25. Brown-Riggs C. Nutrition and health disparities: the role of dairy in improving minority health outcomes. Int J Environ Res Public Health 2015;1(1):ijerph13010028. 26. USDA, Agricultural Research Service; Hoy KM, Goldman, JD. Calcium intake of the U.S. population: What We Eat in America, NHANES 20092010 [cited 2016 Aug 23]. Available from: http://www.ars.usda.gov/ SP2UserFiles/Place/80400530/pdf/DBrief/13_calcium_intake_0910.pdf.
Serum calcium and its complex association with incident type 2 diabetes1 Ranee Chatterjee and Pao-Hwa Lin* Department of Medicine, Duke University School of Medicine, Durham, NC
Type 2 diabetes is a worldwide epidemic that disparately affects certain populations. Obesity is a leading risk factor for type 2 diabetes and has been the main focus for preventive efforts. However, obesity continues to be a serious health issue in the United States, and preventive efforts have not been fruitful. In addition to obesity, other risk factors, such as the one suggested by Rooney et al. (1) in this issue of the Journal, imply opportunities for the development of new prevention strategies. In this study, the investigators evaluated serum calcium as a potential risk factor for incident diabetes in a large biracial prospective cohort from the ARIC (Atherosclerosis Risk in Communities) study. They also evaluated possible racial differences in the association between serum calcium and diabetes risk. Serum calcium is a vital mineral for many cellular processes that is tightly regulated by 3 main mechanisms, including renal filtering and reabsorption of calcium, bone turnover, and intestinal absorption of dietary calcium (diet or supplements) (2). In turn, these mechanisms are regulated by several endogenous factors, including parathyroid hormone, parathyroid hormone–related peptide, vitamin D, ionized calcium, and receptors for these factors, and renal function (2). Serum calcium, as well as each of these other endogenous factors, has been associated with altered glucose metabolism—which affects b cell function or insulin sensitivity—and for some, with even longer-term diabetes risk (3–8). Although the exact mechanism by which serum calcium may relate to diabetes risk is unclear, earlier studies suggested that one possible mechanism is that higher intracellular calcium may decrease the effect of insulin in adipocytes by reducing glucose transporters, in particular the glucose transporter type 4 (GLUT4) and insulin receptor activity (9, 10). In the study by Rooney et al. (1) the investigators found that, compared with those in the lowest quintile of serum calcium concentrations, participants in the highest quintile had a higher risk of diabetes. Such an association was not greatly influenced after adjustment for certain endogenous factors that may influence serum calcium, such as serum parathyroid hormone, vitamin D, and phosphorus. In addition, despite the lack of a significant racial interaction, the positive association between serum calcium and diabetes risk was stronger in African Americans than in whites. Neither the calcium-sensing receptor polymorphisms nor renal function was found to be a significant effect modifier on the association.
In addition to endogenous regulators, exogenous factors may affect serum calcium. The investigators addressed one such common exogenous influence, which is diuretic use. Different types of diuretics affect serum calcium in different ways. Loop diuretics, such as furosemide, increase urinary calcium excretion and can lower serum calcium; thiazide diuretics, which are considered first-line therapy for hypertension (11), decrease urinary calcium excretion and can lead to higher serum calcium concentrations; amiloride, a potassium-sparing diuretic, also leads to a decrease in urinary calcium excretion (12). In this study, although the association persisted after the exclusion of participants taking any diuretic, there was a decrease in the magnitude of the association between serum calcium and diabetes risk. Further study is warranted to determine the prevalence of each type of diuretic use and its respective influence on serum calcium concentrations itself as well as on the association between serum calcium and diabetes risk. Dietary calcium intake is another important exogenous factor for the maintenance of bone and body stores of calcium as well as for serum calcium concentrations; however, when dietary calcium intakes are low, endogenous hormonal factors, especially parathyroid hormone and vitamin D metabolites, act quickly to maintain physiologically viable concentrations of serum calcium (13). Therefore, with this interplay of factors, dietary calcium intake and serum calcium concentrations are not usually observed to correlate tightly. However, the excessive intake of calcium supplements can increase serum calcium concentrations, and a low dietary calcium intake may contribute to lower serum calcium concentrations (13). Unlike the positive association found between serum calcium and diabetes risk, results from observational studies have shown that dietary calcium intake is inversely associated with diabetes risk. The primary source of dietary calcium is from dairy foods and to a lesser extent from certain vegetables and calcium-fortified foods. A higher intake of dairy foods overall has been associated with a lower risk of type 2 diabetes (14, 15); but some studies found that the intake of only certain types of dairy foods, particularly yogurt, is associated with a lower risk of diabetes (15, 16). Some evidence 1
RC was supported by NIH/Duke Clinical and Translational Science award KL2TR001115-02. *To whom correspondence should be addressed. E-mail: pao.hwa.lin@ dm.duke.edu. First published online September 14, 2016; doi: 10.3945/ajcn.116.143321.
Am J Clin Nutr 2016;104:957–8. Printed in USA. Ó 2016 American Society for Nutrition
957
958
EDITORIAL
also suggests that dietary calcium from foods compared with calcium supplements may have differing health benefits; therefore, possible differences in impact on diabetes risk should be investigated (17). The influence of dietary calcium from food and supplements on serum calcium concentrations or on diabetes risk was not addressed in this study. Mechanisms linking dietary calcium or dairy intake and serum calcium to diabetes risk may differ. In the United States, African Americans have a 75% higher prevalence of diabetes compared with whites (18). Although traditional risk factors such as obesity may account for a large proportion of the racial disparity in diabetes risk, they do not account for all of the disparity (19). Rooney et al. examined possible racial differences in the association between serum calcium and diabetes risk. Although they did not find a significant racial interaction, the magnitude of the association was stronger in African Americans than in whites. As described in this study, there are known racial differences in factors that contribute to serum calcium homeostasis that could explain this finding, including racial differences in the endogenous factors that regulate serum calcium, such as renal function, vitamin D, and parathyroid hormone (20–23). In addition, there are racial differences in exogenous contributors to serum calcium concentrations. For the treatment of hypertension, African Americans have been found to be more responsive to thiazide diuretics, and for this group, thiazides are recommended more strongly as a first-line agent for treatment and are used more than for whites (24). The use of thiazides could, in part, explain the higher serum calcium concentrations found in this cohort of African-American participants and should be investigated as a possible confounder of the calcium-diabetes association, particularly among African Americans. There may also be a racial-ethnic disparity in dietary calcium intake from dairy foods. African Americans commonly consume fewer dairy foods than do whites, in part due to either perceived or actual concerns with lactose tolerance (25, 26). The finding that serum calcium concentrations were higher in African Americans than in whites suggests a mechanism that is less likely to be related to dietary intake of calcium. The finding that higher serum calcium is associated with increased diabetes risk is important and needs to be investigated further. As with other risk factors for diabetes, the association between serum calcium and diabetes risk is complex. Further research and understanding of the mechanisms underlying the association between serum calcium and diabetes risk may provide a new opportunity to combat the diabetes epidemic. RC drafted the manuscript, and P-HL critically reviewed and edited the manuscript. Neither of the authors had a conflict of interest to report.
REFERENCES 1. Rooney MR, Pankow JS, Sibley SD, Selvin E, Reis JP, Michos ED, Lutsey PL. Serum calcium and incident type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 2016;104: 1023–9. 2. Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol 2010;5(Suppl 1):S23–30. 3. Kramer CK, Swaminathan B, Hanley AJ, Connelly PW, Sermer M, Zinman B, Retnakaran R. Prospective associations of vitamin D status with beta-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status. Diabetes 2014;63:3868–79. 4. Squires PE, Jones PM, Younis MY, Hills CE. The calcium-sensing receptor and beta-cell function. Vitam Horm 2014;95:249–67.
5. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 2013;36:1422–8. 6. Chang-Chen KJ, Mullur R, Bernal-Mizrachi E. Beta-cell failure as a complication of diabetes. Rev Endocr Metab Disord 2008;9:329–43. 7. Wareham NJ, Byrne CD, Carr C, Day NE, Boucher BJ, Hales CN. Glucose intolerance is associated with altered calcium homeostasis: a possible link between increased serum calcium concentration and cardiovascular disease mortality. Metabolism 1997;46:1171–7. 8. Sun G, Vasdev S, Martin GR, Gadag V, Zhang H. Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population. Diabetes 2005;54:3336–9. 9. Byyny RL, LoVerde M, Lloyd S, Mitchell W, Draznin B. Cytosolic calcium and insulin resistance in elderly patients with essential hypertension. Am J Hypertens 1992;5:459–64. 10. Begum N, Leitner W, Reusch JE, Sussman KE, Draznin B. GLUT-4 phosphorylation and its intrinsic activity: mechanism of Ca(21)-induced inhibition of insulin-stimulated glucose transport. J Biol Chem 1993;268:3352–6. 11. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20. 12. Haas M. The Na-K-Cl cotransporters. Am J Physiol 1994;267:C869–85. 13. Institute of Medicine. Dietary Reference Intakes for calcium and vitamin D. Washington (DC): National Academies Press; 2011. 14. Elwood PC, Pickering JE, Givens DI, Gallacher JE. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids 2010;45:925–39. 15. Tong X, Dong JY, Wu ZW, Li W, Qin LQ. Dairy consumption and risk of type 2 diabetes mellitus: a meta-analysis of cohort studies. Eur J Clin Nutr 2011;65:1027–31. 16. Forouhi NG. Association between consumption of dairy products and incident type 2 diabetes—insights from the European Prospective Investigation into Cancer Study. Nutr Rev 2015;73(Suppl 1):15–22. 17. Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP Diet and Health Study. JAMA Intern Med 2013;173:639–46. 18. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014 [cited 2016 Aug 23]. Available from: https://www.cdc.gov/ diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. 19. Chatterjee R, Brancati FL, Shafi T, Edelman D, Pankow JS, Mosley TH, Selvin E, Yeh HC. Non-traditional risk factors are important contributors to the racial disparity in diabetes risk: the Atherosclerosis Risk in Communities Study. J Gen Intern Med 2014;29:290–7. 20. Guti´errez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011;22:1745–53. 21. Guti´errez OM, Parsa A, Isakova T, Scialla JJ, Chen J, Flack JM, Nessel LC, Gupta J, Bellovich KA, Steigerwalt S, et al. Genetic African ancestry and markers of mineral metabolism in CKD. Clin J Am Soc Nephrol 2016;11:653–62. 22. Palmer Alves T, Lewis J. Racial differences in chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States: a social and economic dilemma. Clin Nephrol 2010;74(Suppl 1):S72–7. 23. Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, Haigh PI, Adams AL. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab 2013;98:1122–9. 24. Flack JM, Sica DA, Bakris G, Brown AL, Ferdinand KC, Grimm RH Jr., Hall WD, Jones WE, Kountz DS, Lea JP, et al. Management of high blood pressure in blacks: an update of the International Society on Hypertension in Blacks consensus statement. Hypertension 2010;56:780–800. 25. Brown-Riggs C. Nutrition and health disparities: the role of dairy in improving minority health outcomes. Int J Environ Res Public Health 2015;1(1):ijerph13010028. 26. USDA, Agricultural Research Service; Hoy KM, Goldman, JD. Calcium intake of the U.S. population: What We Eat in America, NHANES 20092010 [cited 2016 Aug 23]. Available from: http://www.ars.usda.gov/ SP2UserFiles/Place/80400530/pdf/DBrief/13_calcium_intake_0910.pdf.
