Effect of Low-Carbohydrate High-Protein Diets on Acid-Base Balance, Stone-Forming Propensity, and Calcium Metabolism
American Journal of Kidney Diseases 40(2002):265.
by Shalini T. Reddy, MD, Chia-Ying Wang, MD, Khashayar Sakhaee, MD, Linda Brinkley, RD, and Charles Y.C. Pak, MD
American Journal of Kidney Diseases
From the Department of Internal Medicine, Section of General Internal Medicine, The University of Chicago, IL; and the Department of Internal Medicine, Division of General Internal Medicine; and the Center for Mineral Metabolism and Clinical Research, The University of Texas Southwestern Medical Center at Dallas, TX. Supported in part by grants no. P01-DK20543 and M01-RR00633USPHSfrom the US Public Health Service.
Abstract Background: Low-carbohydrate high-protein (LCHP) diets are used commonly for weight reduction. This study explores the relationship between such diets and acid-base balance, kidney-stone risk, and calcium and bone metabolism. Methods: Ten healthy subjects participated in a metabolic study. Subjects initially consumed their usual non-weight-reducing diet, then a severely carbohydrate-restricted induction diet for 2 weeks, followed by a moderately carbohydrate-restricted maintenance diet for 4 weeks. Results: Urine pH decreased from 6.09 (Usual) to 5.56 (Induction; P < 0.01) to 5.67 (Maintenance; P < 0.05). Net acid excretion increased by 56 mEq/d (Induction; P < 0.001) and 51 mEq/d (Maintenance; P < 0.001) from a baseline of 61 mEq/d. Urinary citrate levels decreased from 763 mg/d (3.98 mmol/d) to 449 mg/d (2.34 mmol/d; P < 0.01) to 581 mg/d (3.03 mmol/d; P < 0.05). Urinary saturation of undissociated uric acid increased more than twofold. Urinary calcium levels increased from 160 mg/d (3.99 mmol/d) to 258 mg/d (6.44 mmol/d; P < 0.001) to 248 mg/d (6.19 mmol/d; P < 0.01). This increase in urinary calcium levels was not compensated by a commensurate increase in fractional intestinal calcium absorption. Therefore, estimated calcium balance decreased by 130 mg/d (3.24 mmol/d; P < 0.001) and 90 mg/d (2.25 mmol/d; P < 0.05). Urinary deoxypyridinoline and /V-telopeptide levels trended upward, whereas serum osteocalcin concentrations decreased significantly (P < 0.01). Conclusion: Consumption of an LCHP diet for 6 weeks delivers a marked acid load to the kidney, increases the risk for stone formation, decreases estimated calcium balance, and may increase the risk for bone loss. © 2002 by the National Kidney Foundation, Inc.
OBESITY HAS BECOME a problem of proportions. More than 50% of the US population is either overweight or obese.’ Despite significant advances in approaches to weight reduction, weight management remains a challenging clinical task. Given the lack of facile weight reduction modalities, patients are turning toward alternative therapies, including various weight-reducing diets. Furthermore, because of cultural pressures of Western society, people of normal body weight also choose these weight- reduction diets.
Current popular diets include those that restrict carbohydrate intake, but allow liberal intakes of protein and fat. One of the most popular of these diets is the Atkins’ diet, which imposes a severe restriction on carbohydrate intake to 20 g/d or less for the initial 2 weeks of the diet, with some liberalization of carbohydrate intake after- ward.2 There are no requirements for caloric restriction or adjustments to protein or fat content of this diet. The restriction in carbohydrates leads de facto to an increase in the percentage of protein and fat calories consumed.
There is ample literature on metabolic effects of a high-protein diet alone, without a change in fat or carbohydrate intake. High animal protein intake can confer a marked acid load,3-4 exaggerate urinary stone risk factors (hypercalciuria, hypemricosuria, low pH, and hypocitraturia), and enhance the propensity for crystallization of stone-forming salts (calcium oxalate and uric acid).5’6 High-protein diets also have been associated with negative calcium balance and bone loss.7-11
To the best of our knowledge, no study has examined the effects of a low-carbohydrate high- protein (LCHP) diet, such as the Atkins’ diet,2 on risks for stone formation and bone loss. In addition to effects of high-protein diets alone, it is anticipated that a low-carbohydrate diet will provide an exaggerated acid load through incom-266 REDDYETAL plete oxidation of fat and resultant ketoanion production. This study is designed to examine the effects of an LCHP diet on acid-base balance, stone-forming propensity, and calcium metabolism.
METHODS
Experimental Subjects
Subjects were recruited by advertisement. Included in the study were men and women with a body mass index (BMI) of 22 kg/m2 or greater and a desire to lose weight. Exclusion criteria were the presence or history of peptic ulcer disease, intestinal strictures, chronic diarrhea, renal calculi, metabolic acidosis or alkalosis, osteoporosis, gout, hyperurice- mia, hyperkalemia, hypokalemia, arrhythmias, hypercaice- mia, decreased endogenous creatinine clearance (s=0.6 mL/ min/kg [0.0167 mL/s/kg]), and treatment with drugs that affect acid-base balance or potassium metabolism. Subjects also were excluded if they were currently consuming a weight-reducing diet or could not comply with an inpatient metabolic diet required of the trial.
The study was reviewed and approved by the Institutional Review Board of The University of Texas Southwestern Medical Center (Dallas, TX). The study was performed in its entirety at The Center for Mineral Metabolism and Clinical Research, The University of Texas Southwestern Medical Center. Informed consent was obtained from all subjects. Metabolic Study
All subjects participated in the three stages of the study in the same sequence. Subjects remained on their usual non- weight-reducing diet for the first 2 weeks (usual diet). Subjects then consumed an Atkins’-type induction diet for 2 weeks (induction diet), followed by an Atkins’-type maintenance diet for 4 weeks (maintenance diet).2 For each subject, the usual, induction, and maintenance diets were calculated to be isocaloric and of similar micronutrient composition. The liberal intake of protein during the induction and maintenance diets precluded the restriction of phosphorus and sulfur intake. During the last week of each diet, subjects consumed constant metabolic meals. Subjects were provided with frozen meals for the first 3 days when outpatient and freshly prepared meals served in the General Clinical Research Center (GCRC) for the last 4 days when inpatient. Subjects were instructed to consume only the meals and deionized water provided by the metabolic kitchen. Portions of meals not consumed were returned to the GCRC. Total fluid intake was kept constant at 3 L. Perspiration-inducing physical exercise was prohibited. During the first week of the usual diet, subjects remained on their usual diet at home and kept a diary of food consumed. The dietitian constructed metabolic diets by gathering information from diet diaries and interviews with subjects. During the second week, a constant metabolic diet was provided to subjects as described. After completing the usual diet, subjects were given a copy of Atkins’ diet book.2 After a personal interview with the dietitian regarding contents and restrictions of the diet, subjects began a weight-reducing diet conforming to the Atkins’ induction diet.2 Subjects ate the induction diet at home, choosing their own food items during the first week. Subjects met with a dietitian during the outpatient diet stage to confirm adherence to the induction diet. Metabolic diets were constructed from a second food diary and another direct interview. Carbohydrate content was adjusted to achieve and maintain positive urine ketones, as directed by Atkins.2 Atkins recommends using lipolysis-testing strips to measure ketones daily during the induction diet to determine whether lipolysis has commenced. Subjects who have negative ketone test results are advised to progressively reduce carbohydrate consumption until ketone test results become positive.2
During the first 3 weeks of the maintenance diet, subjects ate the Atkins’ maintenance diet at home while choosing their own food items. Food diaries and direct interviews again were used to construct constant metabolic diets consumed during the last week. Subjects met with a dietician during the outpatient diet stage to confirm adherence to the maintenance diet. Urine ketones were monitored, and carbohydrate content was adjusted to comply with Atkins’ recommendations.2
Throughout the entire study, all subjects took a daily multivitamin tablet (Mission Pharmacal Co, San Antonio, TX).
Laboratory Tests
Laboratory studies were performed during the last week of each stage. Two 24-hour urine samples were collected days 6 and 7 for the measurement ofpH, citrate, ammonium, sulfate, titratable acidity, calcium, uric acid, oxalate, phosphorus, sodium, potassium, magnesium, creatinine, total volume, deoxypyridinoline (DPD), and W-telopeptide (NTX). Fasting venous blood samples were obtained on the mornings of days 7 and 8 for sodium, potassium, chloride, total carbon dioxide, blood urea nitrogen, calcium, magnesium, phosphorus, alkaline phosphatase, and creatinine, as well as parathyroid hormone (PTH), 1,25-(OH)2 vitamin D (calcit- riol), bone-specific alkaline phosphatase, and osteocalcin.
On the morning of day 8, a 2-hour fasting urinary calcium sample was obtained. Fractional intestinal calcium absorption was measured using a dual-tracer stable isotope technique.12 This technique measures unidirectional flux of calcium across the intestinal lumen. First, calcium 42 (^Ca), 20.0 jLLg, is administered intravenously. Then oral calcium is administered as ^Ca, 1.0 mg, mixed in 250 mL of a standardized liquid synthetic diet containing 100 mg of elemental calcium as a carrier. The receptacle containing the liquid synthetic diet and ^Ca is rinsed with 50 mL of distilled water that is swallowed by the study subject. Body weight, supine blood pressure, and pulse were measured day 7.
Analytical Procedures
Serum electrolytes, blood urea nitrogen, calcium, magnesium, phosphorus, alkaline phosphatase, and creatinine were analyzed as part of a sequential multiple analyzer-20 (SMA- 20). Serum osteocalcin level was determined using immuno- radiometric assay (IRMA) Kit (Immutropics, San Clemente, CA). Intact PTH was measured using a radioimmunoassay kit (Nichols’ Institute, San Juan Capistrano, CA). Serum calcitriol was measured using a competitive radioactive ligand-binding assay, and bone-specific alkaline phospha- tase was determined using an enzyme-linked immunosor- bent assay (ELISA; Metra Biosystems Inc, Mountain View, CA).
Urinary calcium and magnesium were analyzed by atomic absorption spectrophotometry; sodium and potassium, by flame photometry; and sulfate and oxalate, by ion chromatog- raphy. An autoanalyzer was used to determine urinary creat- inine, phosphorus, uric acid, ammonium, citrate, and sulfate levels. Urine bicarbonate concentration was calculated using the Henderson-Hasselbalch equation. The urinary concentration of titratable acidity was measured directly by titrating undiluted urine collected for 24 hours under mineral oil to 7.40 by using an automated burette end-point titration system (Radiometer; Hatch Co, Loveland, CO). Net acid excretion was calculated as the sum of urinary titratable acidity and ammonium minus the calculated urinary bicarbonate.
Urinary DPD was analyzed by the Pyrilinks-D ELISA (Metra Biosystems Inc). NTX was determined by the Osteo- mark ELISA (Ostex, Seattle, WA). Values for DPD and NTX were not corrected for creatinine excretion because urinary creatinine levels could be elevated secondary to increased consumption of meat.
Relative saturation ratios (RSRs) of calcium oxalate, brushite (CaHPO^^HaO), and monosodium urate were calculated by dividing the ionic activity product in actual urine samples by the respective thermodynamic solubility product,13 using the EQUIL2 computer program of Finlayson (Gainesville, FL).14 A value of 1 represents saturation; greater than 1, supersaturation; and less than 1, undersaturation. Estimated calcium balance was calculated as the difference between estimated total calcium absorbed (product of dietary calcium and fractional intestinal calcium absorption) and urinary calcium loss.15 Statistical Analysis
Repeated-measures analysis of variance was performed to assess differences in calcium balance and serum and urine biochemistry results among the three dietary stages. When analysis of variance was significant (P < 0.05) or showed a trend, paired Mests were used to compare induction and maintenance diets with the usual diet. Statistical analyses were performed using SAS version 8.0 (SAS Institute, Cary, NC). Results are expressed as mean ± SD unless otherwise stated.
RESULTS
Baseline Demography
Eighty volunteers were screened for the study. Ten healthy subjects (seven women, three men; age, 21 to 52 years; mean, 38.4 years) participated in the study. Three subjects were Latin American, and seven subjects were white. At entry, subjects had a mean height of 166 cm (range, 152 to 189 cm), mean weight of 81.4 kg (range, 56.7 to 109.9 kg), and mean BMI of 29.4 kg/cm2 (range, 22.0 to 38.3 kg/cm2). Composition of Metabolic Diets
The composition of each subject’s three different metabolic diets was estimated by using US Department of Agriculture food tables16 and a database generated by our GCRC of analyzed contents of individual food components used in the metabolic diets. The amount consumed was determined by subtracting the amount of uncon- sumed returned food from the food provided (Table 1). Compared with the usual diet, induction and maintenance diets had nearly twofold greater protein and fat contents and significantly lower carbohydrate content. Amounts of calcium, magnesium, sodium, potassium, and chloride did not differ significantly among the diets. The induction and maintenance diets had significantly greater contents of phosphorus, sulfur, and acid ash compared with the usual diet. Protein was primarily derived from meat. The ox- alate content of the induction and maintenance diets was lower than that of the usual diet, reaching statistical significance for the induction diet.
Adherence to the diet is reflected in the statistically significant weight loss (usual diet, 81.3 ± 18.5 kg; induction, 78.4 ± 18.1 kg; P < 0.001; maintenance, 77.2 ± 17.5 kg; P < 0.001) and significant increase in blood urea nitrogen levels (Table 2). In addition, seven subjects had positive urine ketones during the induction diet. The remaining three subjects were persistently negative for urine ketones despite reductions in carbohydrate intake to 15 to 20 g/d or 3% to 4% of total daily caloric intake during the inpatient supervised metabolic diets. Effects on Acid-Base Balance
Serum sodium levels were slightly but significantly lower during the induction and maintenance diets compared with the usual diet (Table 2). None of the subjects developed a clinically detectable metabolic acidosis. Serum, potassium, chloride, carbon dioxide, calcium, and phosphorus levels remained unchanged. Urinary pH and citrate values decreased significantly in the induction and maintenance diets compared with the usual diet (Figs 1 and 2).
Effects on Urinary Saturation of Stone-Forming Salts
Compared with the usual diet, urinary calcium and phosphorus levels increased substantially by approximately 90 mg/d (2.25 mmol/d) and 500 mg/d (12.48 mmol/d) during the LCHP diets, respectively (Tables 3 and 4). Urinary uric acid, oxalate, sodium, potassium, and total volume did not differ significantly among the three diets. Urinary magnesium level decreased during both LCHP diets.
Baseline weight correlated with baseline daily caloric intake (r = 0.76; P = 0.01). Baseline caloric intake also correlated with the incremental increase in urinary sulfate excretion from the usual to the induction diet (r = 0.72; P = 0.02). Effect on Calcium Metabolism
Whereas dietary calcium intake remained unchanged or modestly decreased (Table 1), urinary calcium excretion increased significantly during both LCHP diets compared with the usual diet (Table 3). Fractional intestinal calcium absorption was unchanged. Estimated calcium balances decreased during the induction and maintenance diets by 130 mg/d (3.24 mmol/d) and 90 mg/d (2.25 mmol/d) from the usual diet, respectively (Fig 3). Fasting urinary calcium levels were significantly greater during LCHP diets from the usual diet. Serum calcium and phosphorus levels did not differ significantly among the three diets (Table 3). Total serum alkaline phosphatase levels decreased significantly during LCHP diets from the usual diet, but bone-specific alkaline phosphatase levels did not differ. Serum osteocalcin levels were significantly lower during LCHP diets. Although not statistically significant, there was an upward trend in urinary DPD and NTX levels (Table 3). There was no significant difference in serum PTH and calcitriol levels among the three diets (Table 3). Compared with the usual diet, endogenous creatinine clearance was significantly higher during both LCHP diets (Table 4).
DISCUSSION
The objective of this study is to examine the effects of LCHP weight-reducing diets on acid- base balance, stone-forming propensity, and calcium metabolism in healthy individuals. Our data show that such a diet provides an exaggerated acid load, increasing risks for renal calculi formation and bone loss.
The increased acid load delivered by an LCHP diet was reflected in the increased urinary titrat- able acidity and urinary ammonium excretion. These diets were associated with a striking increase in net acid excretion by approximately 50 mEq/d, presumably derived from the combined effects of a high-protein and low-carbohydrate diet. Other changes in urinary biochemistry results related to the acid load were also detected, including decreased urinary pH and citrate values and increased urinary calcium levels. Acid load was adequately compensated because systemic metabolic acidosis did not develop.
The source of the increased acid load from an LCHP diet is likely twofold. LCHP diets tend to be high in animal proteins that are rich in sulfur- containing amino acids. Oxidation of sulfur to sulfate generates protons.17 In this study, LCHP diets had a much greater content of sulfur and acid ash than the usual diet. A severe restriction of carbohydrates may also cause production of keto-acids.18 Our data are consistent with previous reports showing that high-protein diets deliver an exaggerated acid load.3’19’20
The changes in urinary biochemistry cited enhance the propensity for the formation of uric acid and calcium stones. At a urine pH of 5.35, the pKa of uric acid, uric acid is sparingly soluble in the urinary environment and may precipitate and form uric acid stones and/or in- duce heterogeneous nucleation of calcium ox- alate crystals, thus promoting the formation of calcium oxalate stones.21 Urinary pH decreased from approximately 6.0 during the usual diet to 5.5 during LCHP diets, reducing the pH closer to the dissociation constant of uric acid. The mean concentration of undissociated uric acid increased to more than twice the previously reported solubility of uric acid.22 The RSR of calcium oxalate was not increased, likely because of the small study size and in part because of urine dilution by the imposition of a high-fluid intake. However, LCHP diets increased urinary calcium by approximately 60% and significantly decreased urinary citrate, an inhibitor of calcium stone formation.23 These results confirm previous reports noting a positive correlation between animal protein consumption and risk for kidney stone disease.7’24’26
Findings of this study may underestimate changes in stone risk factors for overweight individuals consuming an LCHP diet. Lemann et al27 showed that for a given amount of oxalate intake, urine oxalate excretion correlated positively with body weight. In our study, baseline body weight did not correlate with any incremental increases in stone risk factors for the induc-tion or maintenance diets. However, the study size may have been too small to detect these relationships. In addition, the wide range of body sizes among participants could have masked positive findings in larger individuals. In our study, 2 of the 10 subjects had a BMI less than 25 kg/m2. The criterion to include subjects with a BMI of 22 kg/m2 or greater was chosen to include normal body mass because some individuals in the general public may choose this diet to lose weight despite having a normal BMI. Had there been more subjects of larger body size, a more striking increase in urinary oxalate levels between the baseline and LCHP diets might have been apparent.
In our study, fluid intake was fixed to eliminate urine volume as a confounding factor in urinary stone risk. The purpose of this study is to evaluate effects of an LCHP diet, not to reassess known effects of varying urine volumes on the 272 REDDYETAL risk for stone formation.28 Three liters of fluid per day was selected for all three dietary stages of this study; 1 L for insensible fluid losses, and the remaining 2 L to prevent spontaneous precipitation of calcium-containing stones under conditions of normal urinary calcium excretion (100 to 200 mg/d; 2.50 to 4.99 mmol/d). Three liters of fluid intake is greater than the intake previously reported among healthy subjects consuming a self-selected diet.27 Ad lib fluid intake may have resulted in a greater increase in risk for stone formation. Therefore, it appears reasonable to suggest that individuals consuming an Atkins’- type diet should maintain a high fluid intake to help decrease the propensity for stone formation.
Hypercalciuria detected during LCHP diets most likely resulted from the acid load. Previous studies have shown that urinary calcium levels vary directly with net acid excretion, reviewed by Lemann.4 Enhanced hyperfiltration of calcium from an increased glomerular filtration rate, impaired renal tubular calcium reabsorption, and cation trapping by sulfate and phosphate may contribute to enhanced renal calcium excretion.29-31
Fractional intestinal calcium absorption did not significantly change during LCHP diets. Our data are consistent with past reports showing that a high-protein diet produces no significant change in fractional intestinal calcium absorption and therefore predisposes to negative calcium balance.10’32
It is not possible to ascertain from this study whether bone turnover was affected directly by LCHP diets. Although not statistically significant, urinary DPD and NTX levels, markers of bone resorption, trended upward during the maintenance diet. Serum osteocalcin levels declined significantly. Results of this study are supportive of previous in vitro experiments showing chronic metabolic acidosis enhances bone resorption and diminishes bone formation.33 The lack of a significant change in bone resorption markers is not surprising because of the small sample size, short study duration, and large coefficient of variation inherent in assays. A review of the literature shows conflicting effects of a high animal protein diet on bone turnover. Short-term controlled dietary studies34-36 and a cross-sectional37 survey suggest high-protein diets are associated with increased bone turnover. Two studies evaluating hip fracture incidence suggest that lower protein intake is associated with increased hip fractures.38’39 Other studies suggest bone mineral density is better maintained with high-protein diets,40 although perhaps only in premenopausal women.41 The source of protein may influence the effects seen.42 A detailed metabolic study of normal postmenopausal women suggested that acid retention from relative animal protein excess could impair bone formation and stimulate bone resorption.35
Our study represents a metabolic study of short duration in a limited number of subjects. However, acid excess will be sustained as long as carbohydrate restriction and high-protein intake are maintained. Thus, the increased risk for stone formation might be expected during the entire duration of such a diet.
Implications from this study on long-term effects on stone-forming propensity and bone metabolism must be explored in a prospective long- term trial. Nevertheless, this short-term metabolic study stresses that an LCHP weight-reducing diet may enhance the risk for stone formation and bone loss. Because these potential complications probably are produced by the exaggerated acid load, preliminary studies showing the potential value of alkali therapy should be expanded.35’43 Further examination of chronic effects on bone is warranted. Patients who choose to pursue weight reduction through carbohydrate- restricted diets should be made aware of a potential increase in risk for kidney stone formation and the unknown long-term risk to bone health.
In conclusion, low-carbohydrate diets are popular and are consumed by many people in an attempt to reduce their weight. Our study shows that such a diet delivers an exaggerated acid load. Clinical implications of this enhanced acid load include an increase in kidney stone risk, decrease in estimated calcium balance, and potential increase in risk for bone loss.
REFERENCES
Kuczmarski RJ, Can-oil MD, Flegal KM, Troiano RP: Varying body mass index cutoff points to describe overweight prevalence among US adults: NHANES III (1988 to 1994). Obes Res 5:542-548, 1997
Atkins RC: Dr Atkins’ New Diet Revolution. New York, NY, Avon, 1997
Ball D, Maughan RJ: Blood and urine acid-base status of premenopausal omnivorous and vegetarian women. Br J Nutr 78:683-693, 1997
Lemann J Jr: Relationship between urinary calcium and net acid excretion as determined by dietary protein and potassium: A review. Nephron 81:S18-S25, 1999 (suppi 1)
Robertson WG, Heyburn PJ, Peacock M, Hanes FA, Swaminathan R: The effect of high animal protein intake on the risk of calcium stone formation in the urinary tract. Clin Sci (Colch) 57:285-288, 1979
Fellstrom B, Danielson BG, Karlstrom B, Lithell H, Ljunghall S, Vessby B: The influence of a high dietary intake of purine-rich animal protein on urinary urate excretion and supersaturation in renal stone disease. Clin Sci (Colch) 64:399-405, 1983
Fellstrom B, Danielson BG, Karlstrom B, et al: Effects of high intake of dietary animal protein on mineral metabolism and urinary supersaturation of calcium oxalate in renal stone formers. Br J Urol 56:263-269, 1984
Anand CR, Linkswiler HM: Effect of protein intake on calcium balance of young men given 500 mg calcium daily. JNutr 104:695-700, 1974
Linkswiler HM, Zemel MB, Hegsted M, Schuette S: Protein-induced hypercalciuria. Fed Proc 40:2429-2433, 1981
Johnson NE, Alcantara EN, Linkswiler H: Effect of level of protein intake on urinary and fecal calcium and calcium retention of young adult males. J Nutr 100:1425- 1430,1970
Alien LH, Oddoye EA, Margen S: Protein-induced hypercalciuria: A longer term study. Am J Clin Nutr 32:741- 749,1979
Abrams SA, Esteban NV, Vieira NE, Sidbury JB, Specker BL, Yergey AL: Developmental changes in calcium kinetics in children assessed using stable isotopes. J Bone Miner Res 7:287-293, 1992
Pak CY, Hayashi Y, Finlayson B, Chu S: Estimation of the state of saturation of brushite and calcium oxalate in urine: A comparison of three methods. J Lab Clin Med 89:891-901, 1977
Werness PG, Brown CM, Smith LH, Finlayson B: EQUIL2: A basic computer program for the calculation of urinary saturation. J Urol 134:1242-1244, 1985
Pak CY, Stewart A, Raskin P, Galosy RA: A simple and reliable method for calcium balance using combined period and continuous fecal markers. Metabolism 29:793- 796,1980
US Department of Agriculture, Agricultural Research Service: Composition of Foods. Agriculture Handbook No. 8, Series 8-1 to 8-16. Washington, DC, Government Printing Office, 1976-1987
Tschope W, Ritz E: Sulfur-containing amino acids are a major determinant of urinary calcium. Miner Electrolyte Metab 11:137-139, 1985
Bois-Joyeux B, Chanez M, Azzout B, Delhomme B, Peret J: Comparison between starvation and consumption of a high protein diet in rats: Hepatic metabolites and amino acid levels during the first 24 hours. Diabetes Metab 12:239- 245,1986
Greenhaff PL, Gleeson M, Maughan RJ: The effects of dietary manipulation on blood acid-base status and the performance of high intensity exercise. Eur J Appi Physiol Occup Physiol 56:331-337, 1987
Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A: Effect of diet on plasma acid-base composition in normal humans. Kidney Int 24:670-680, 1983
Coe FL, Strauss AL, Tembe V, Le Dun S: Uric acid saturation in calcium nephrolithiasis. Kidney Int 17:662- 668, 1980
Coe FL: Uric acid and calcium oxalate nephrolithiasis. Kidney Int 24:392-403, 1983
Pak CY: Citrate and renal calculi: An update. Miner Electrolyte Metab 20:371-377, 1994
Kok DJ, lestra JA, Doorenbos CJ, Papapoulos SE: The effects of dietary excesses in animal protein and in sodium on the composition and the crystallization kinetics of calcium oxalate monohydrate in urines of healthy men. J Clin Endocrinol Metab 71:861-867, 1990
Schuette SA, Zemel MB, Linkswiler HM: Studies on the mechanism of protein-induced hypercalciuria in older men and women. J Nutr 110:305-315, 1980
Robertson WG, Peacock M, Hodgkinson A: Dietary changes and the incidence of urinary calculi in the UK between 1958 and 1976. J Chronic Dis 32:469-476, 1979
Lemann J Jr, Pleuss JA, Worcester EM, Homick L, Schrab D, Hoffmann RG: Urinary oxalate excretion increases with body size and decreases with increasing dietary calcium intake among healthy adults. Kidney Int 49:200- 208,1996
Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A: Urinary volume, water and recurrences in idio- pathic calcium nephrolithiasis: A 5-year randomized prospective study. J Urol 155:839-843, 1996
Kim Y, Linkswiler HM: Effect of level of protein intake on calcium metabolism and on parathyroid and renal function in the adult human male. J Nutr 109:1399-1404, 1979
Zemel MB, Schuette SA, Hegsted M, Linkswiler HM: Role of the sulfur-containing amino acids in protein- induced hypercalciuria in men. J Nutr 111:545-552, 1981
King AJ, Levey AS: Dietary protein and renal function. J Am Soc Nephrol 3:1723-1737, 1993
Heaney RP: Dietary protein and phosphorus do not affect calcium absorption. Am J Clin Nutr 72:758-761, 2000
Bushinsky DA, Frick KK: The effects of acid on bone. Curr Opin Nephrol Hypertens 9:369-379, 2000
Kerstetter JE, Mitnick ME, Gundberg CM, et al: Changes in bone turnover in young women consuming different levels of dietary protein. J Clin Endocrinol Metab 84:1052-1055, 1999
Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris RC Jr: Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engi J Med 330:1776-1781, 1994
Licata AA, Bou E, Bartter FC, West F: Acute effects of dietary protein on calcium metabolism in patients with osteoporosis. J Gerontol 36:14-19, 1981
Itoh R, Suyama Y, Oguma Y, Yokota F: Dietary sodium, an independent determinant for urinary deoxypyr- idinoline in elderly women. A cross-sectional study on the effect of dietary factors on deoxypyridinoline excretion in 24-h urine specimens from 763 free-living healthy Japanese. Eur J Clin Nutr 53:886-890, 1999
Frassetto LA, Todd KM, Morris RC Jr, Sebastian A: Worldwide incidence of hip fracture in elderly women: Relation to consumption of animal and vegetable foods. J Gerontol A Biol Sci Med Sci 55:M585-M592, 2000
Munger RG, Cerhan JR, Chiu BC: Prospective study of dietary protein intake and risk of hip fracture in postmeno- pausal women. Am J Clin Nutr 69:147-152, 1999
Hannan MT, Tucker KL, Dawson-Hughes B, Cupples LA, Felson DT, Kiel DP: Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study. J Bone Miner Res 15: 2504-2512,2000
Cooper C, Atkinson EJ, Hensrud DD, et al: Dietary protein intake and bone mass in women. Calcif Tissue Int 58:320-325,1996
Sellmeyer DE, Stone KL, Sebastian A, Cummings SR: A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group. Am J Clin Nutr 73:118-122, 2001
Lutz J: Calcium balance and acid-base status of women as affected by increased protein intake and by sodium bicarbonate ingestion. Am J Clin Nutr 39:281-288, 1984