| | Effect of Carbohydrate-Electrolyte Sports Beverages on Urinary Stone Risk FactorsReceived 7 January 2009 published online 21 July 2009.
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Mechanism Underlying the Low Prevalence of Pediatric Calcium Oxalate Urolithiasis
, 21 July 2009
Chikahiro Momohara, Masao Tsujihata, Iwao Yoshioka, Akira Tsujimura, Norio Nonomura, Akihiko Okuyama
The Journal of Urology
September 2009 (Vol. 182, Issue 3, Pages 1201-1209)
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PurposeWe evaluated the effects of consuming carbohydrate-electrolyte sports beverages (Gatorade®) on urinary stone risk factors. Materials and MethodsTwelve normal subjects (5 men, 7 women) and 12 hypercalciuric stone formers (2 men, 10 women) participated in a 4-week prospective, crossover study consisting of 3 study phases. In phase 1 subjects were placed on a monitored stone prevention diet that was continued throughout the study. In phase 2 subjects ingested 2 l Gatorade daily followed by a 7-day washout period. In phase 3 subjects ingested 2 l water daily. On the final day of phases 1, 2 and 3 a 24-hour urine collection and blood sample were analyzed for stone risk factors. Effects of group and phase were tested using repeated measures ANOVA and paired t tests. ResultsChanges in urinary risk factors after Gatorade consumption revealed no statistically significant difference between normal subjects and stone formers. However, intrasubject variation occurred in both groups. Gatorade consumption in both groups increased urinary pH (p = 0.006), urinary chloride (p = 0.044) and urinary sodium (p = 0.008), and decreased urinary potassium (p = 0.035) and urinary uric acid (p = 0.019) in a statistically significant manner. In response to Gatorade consumption urinary volume, calcium and citrate were unchanged compared to water consumption and baseline. ConclusionsGatorade increased mean urinary sodium and chloride levels compared to water and baseline. However, the results were within normal urinary parameters. The change did not appear to be clinically significant as urinary calcium was unchanged. Overall consumption of Gatorade does not increase or decrease urinary stone risk factors. The multifactorial disease urolithiasis has an estimated prevalence of 1% to as high as 5% in industrialized countries.1 Among afflicted individuals approximately 50% will experience at least 1 recurrence of stone formation within 10 years of the first episode.2 Not only does urolithiasis negatively affect quality of life but it also has a high monetary cost. In 2000 the annual expenditure for individuals filing claims for nephrolithiasis related events was more than $2 billion, which includes direct costs of disease treatment as well as indirect costs related to loss of productivity.3 Epidemiological factors that influence stone formation include diet, genetics, age, sex and geographic location. Although the effect of numerous beverages on urinary stone risk factors has been extensively reported, the effect of the popular carbohydrate-electrolyte sports beverage Gatorade is not well documented. We evaluated the effects of consuming carbohydrate-electrolyte sports beverages such as Gatorade on urinary stone risk factors. Methods  After obtaining institutional review board approval we enlisted 14 normal subjects (group A) and 15 hypercalciuric stone formers (group B) to participate in a 4-week prospective crossover study from May 2005 to April 2006. Exclusion criteria were taking protease inhibitors, having renal insufficiency, recurrent or active urinary tract infections as defined by more than 2 positive urine cultures per year, acid-base disorders including renal tubular acidosis, a history of diabetes mellitus, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, Crohn's disease, ulcerative colitis, short gut syndrome, celiac sprue, primary gout or any other debilitating chronic illness. All participants provided written informed consent with guarantees of confidentiality. Of these individuals 2 normal subjects and 3 hypercalciuric stone formers dropped out of the study, leading to the exclusion of their results from statistical analysis. One patient was unable to collect the 24-hour urine sample correctly thus the sample was not adequate for processing, another dropped out of the study electively secondary to chronic ear infections, 1 found the diet too restrictive, and 2 were lost to followup and did not show up for study visits. The study was 4 weeks long and consisted of 3 phases lasting 7 days each in addition to a 7-day washout period. On the final day of phases 1, 2 and 3 a 24-hour urine collection and blood sample were obtained for analysis. During the first phase all subjects met with our Stone Clinic dietitian and were placed on a standardized stone prevention diet consisting of no added sodium, avoidance of foods containing high amounts of oxalate, restriction of animal proteins and adequate calcium intake as specified by the recommended daily allowance. The subjects were asked to abide by this diet for the duration of the study including the washout phase. All subjects were required to keep a specific food diary 3 days of the week which was reviewed by our dietitian throughout the study. Dietary modifications were recommended if the subject strayed from the stone prevention diet. After following the stone prevention diet for 1 week a baseline 24-hour urine sample and serum for a basic metabolic panel were collected. In the second phase of the study all subjects ingested 2 l Gatorade daily for 7 days with collection of a 24-hour urine and serum blood work at phase end. This was followed by a 7-day washout period during which subjects had no restrictions or specific requirements relating to beverage consumption. In the final phase of the study all subjects ingested 2 l water daily followed by collection of the final 24-hour urine and serum blood work. Basic descriptive statistics and frequencies were used to describe all variables. Effects of group phase and group by phase interaction were tested using repeated measures ANOVA and paired Student's t tests. Probability values less than 0.05 were considered statistically significant. Statistical analysis was performed using SAS®. Results  For the final analysis group A consisted of 12 normal subjects (mean ± SD age 36.3 ± 10.6 years) and group B included 12 hypercalciuric stone formers (mean ± SD age 38.8 ± 7.7 years). Statistically significant changes in serum levels of sodium, potassium and BUN occurred with Gatorade consumption but did not appear to be clinically significant as the results remained within the range of normal serum levels (table 1). Evaluation of changes in urinary risk factors after Gatorade consumption revealed no statistically significant difference between normal subjects and stone formers. However, both groups showed intragroup variation in urinary pH (p = 0.006), urinary chloride (p = 0.044), urinary sodium (p = 0.008), urinary potassium (p = 0.035) and urinary uric acid (p = 0.019). Among normal subjects and stone formers Gatorade consumption significantly increased mean urinary pH (group A 6.17 vs 6.58, group B 6.42 vs 7.08) and mean urinary chloride (group A 108 vs 132 mEq/24 hours, group B 87 vs 138 mEq/24 hours) compared to baseline (table 2, fig. 1). When Gatorade consumption was compared to water consumption mean urinary sodium (group A 158 vs 102 mEq/24 hours, group B 170 vs 149 mEq/24 hours) and mean urinary potassium levels (group A 50 vs 43 mEq/24 hours, group B 57 vs 49 mEq/24 hours) increased significantly in both groups (fig. 2). Urinary uric acid supersaturation decreased after consumption of Gatorade compared to baseline (group A 1.7 vs 0.6, group B 0.85 vs 0.22) while urinary volume, calcium and citrate did not change when comparing Gatorade consumption to water and baseline (fig. 3). Discussion  Although numerous intrinsic and extrinsic factors influence the formation of kidney stones, low urinary volume and dehydration have a predominant role. Low urinary volume is the most commonly encountered abnormality among stone formers and, not surprisingly, urine volume exceeding 2 l daily significantly decreases the risk of stone disease, likely through the presumed dilutional effect of increased urine volume on lithogenic factors.1 Thus, populations exposed to high ambient temperatures, high degrees of physical activity and insufficient hydration have a high incidence and prevalence of urolithiasis.4 An increase in fluid intake is the primary modality for the prevention of urolithiasis, and the most important therapeutic measure regardless of stone composition or stone formation etiology.3, 5, 6 Recent epidemiological and short-term studies of urinary composition in response to dietary changes have analyzed the effects of specific beverages on the risk of stone formation in the general population.7, 8, 9 For example citrus beverages, particularly lemon juice, orange juice and lemonade, have been associated with decreased urinary lithogenicity. The high levels of citrate found in orange and lemon juice alkalinize the urine, stimulate calcium reabsorption and inhibit calcium crystal growth aggregation.9 The protective nature of beverages high in citrate may also be due to a reduction in urinary calcium excretion.10 However, due to the different amounts of potentially lithogenic substances found in many of the beverages examined, studies have yielded highly variable results. Many beverages have proven controversial with regard to their lithogenic effect. McHarg et al reported that cranberry juice has antilithogenic properties in that consumption resulted in a decrease in oxalate excretion, a decrease in relative supersaturation of calcium oxalate and a resultant increase in urinary citrate.11 Conversely Gettman et al reported mixed effects on urinary stone risk factors after consumption of cranberry juice.12 In their study cranberry juice increased urinary calcium and oxalate levels, decreased pH levels but did not alter urinary citrate levels. Cranberry concentrate tablets were also shown to increase the risk of stone formation by increasing urinary oxalate levels.13 Similar debate surrounds the effect of grapefruit juice. Curhan et al reported epidemiological data derived from the Nurses' Health Study I and II, and the Health Professionals Follow-Up Study that suggest grapefruit juice was associated with increased lithogenicity related to increased urinary oxalate levels.8, 9 While Goldfarb and Asplin noted an increase in urinary citrate and oxalate content with grapefruit juice consumption, they did not demonstrate any clinically significant changes related to lithogenicity.10 Paradoxically coffee and tea were protective against stone formation despite containing high levels of oxalates.7 Carbonated beverages, a staple of the American diet, have been associated with an increased risk of stone formation due in large part to increased levels of urinary oxalates.14 However, recently presented data from Abbott and Goodman demonstrated that cola does not increase urinary stone risk factors.15 In a recent large prospective analysis of 3 cohorts, The Nurses' Health Study I and II, and the Health Professionals Follow-Up Study, Taylor and Curhan reported an independent association between increased risk of incident kidney stones and fructose intake, but no association with the intake of nonfructose carbohydrates.16 The mechanisms underlying the relation between stone risk and fructose consumption remain unknown, but may be secondary to resultant hypercalciuria, hyperoxaluria, decreased urinary pH and increased urinary uric acid. Little is known about the influence of carbohydrate-electrolyte sport beverages such as Gatorade on stone formation but based on their varying composition increased and decreased urine lithogenicity could be expected. While the content of citrate would be expected to increase urine citrate excretion and urine pH, and provide protection against calcium and uric acid stones, the sodium content of sports beverages promoted as useful for rehydration in athletes might be associated with increases in urine calcium excretion.16 However, since these beverages are low in oxalate forming compounds and are designed to facilitate rehydration, they may be protective in nature. According to the Gatorade Sports Science Institute the 4 key components of carbohydrate-electrolyte sports beverages that promote rehydration are 1) electrolyte composition (5% RDA sodium and 1% RDA potassium in an 8 oz serving), 2) beverage flavor, 3) optimal carbohydrate composition (6% carbohydrate solution) to assure rapid fluid delivery and carbohydrate use, and 4) maximal fluid osmolality which facilitates gastrointestinal absorption as quickly as water (see Appendix).17 The composition of Gatorade also includes citric acid and sodium citrate, components that increase the alkali load and ultimately cause an increase in urinary citrate and pH levels. Regardless of their hydrating capabilities anecdotal reports of carbohydrate-electrolyte sports beverages promoting lithogenesis exist but have yet to be documented in the literature. The putative lithogenic effect may stem from the high sodium content of these beverages (with an 8 ounce serving accounting for 5% of the RDA of sodium), and the undefined contribution of high fructose corn syrups to nephrolithiasis. Goodman et al recently reported that ingestion of Propel®, a carbohydrate sports drink with more citrate and a higher pH than Gatorade, significantly increased mean urinary citrate excretion and pH compared to water with no significant difference in the excretion of sodium and calcium.18 The varying carbohydrate composition among carbohydrate-electrolyte beverages makes it difficult to extrapolate our results with Gatorade, which contains a 6% carbohydrate mixture of glucose, sucrose and fructose, to those of other beverages. Carbohydrate-electrolyte sports beverages such as Gatorade have become staples in the American diet. Specifically Gatorade commands 80% of the market share of sports drinks in the United States.17 Gross retail of Gatorade surpassed $3 billion in the United States in 2004 with 142 bottles sold in the United States each second.19 Although Gatorade and other carbohydrate-electrolyte sports beverages were initially developed for rehydration of athletes during extreme exercise, the average American now consumes this beverage regardless of athletic prowess or metabolic state. The popularity of this class of beverages underscores the importance of identifying the effect of Gatorade on urinary stone risk factors. Evaluation of changes in urinary risk factors after Gatorade consumption revealed no statistically significant difference between normal subjects and stone formers. However, both groups demonstrated statistically significant intragroup variation in urinary pH, urinary chloride, urinary sodium, urinary potassium and urinary uric acid. Gatorade consumption compared with baseline levels and water consumption had no effect on urinary volume, calcium and citrate levels. Gatorade consumption produced changes in a subset of urinary risk factors. For example, it caused statistically significant differences in the serum levels of sodium, potassium and BUN. However, these values did not appear to be clinically significant because the results remained within respective normal ranges. The increase in mean urinary pH after consumption of Gatorade compared to baseline could be related to the observation of a nonstatistically significant increase in urinary citrate levels. This observation could imply a protective effect in the consumption of Gatorade. The increase in urinary sodium and chloride compared to water consumption and baseline levels is not surprising given the high sodium load (50% RDA) that each subject ingested. However, the values were well within the normal range for urinary parameters and did not appear to be clinically significant. It is also important to note that urinary calcium did not increase after Gatorade consumption even with the increased sodium load. Finally the decrease in urinary uric acid observed after consumption of Gatorade compared to baseline should be noted as another parameter that may be protective against stone formation. However, caution must be advised in the routine consumption of beverages containing high levels of sodium, fructose and carbohydrate as there may be other deleterious health effects. Furthermore, we are not advocating the consumption of these types of beverages rather than water as a means of stone prevention. We are merely highlighting the effects of this beverage type on urinary stone risk factors because they are common in the Western diet. Conclusions  Compared to the consumption of water and baseline, Gatorade consumption increased mean urinary sodium and mean urinary chloride levels. However, the results were within normal limits. The change in these parameters did not appear to be clinically significant because urinary calcium was unchanged. Overall Gatorade consumption does not increase or decrease urinary stone risk factors, and may be protective when considering pH and mean urinary uric acid levels. References  1. 1Delvecchio FC, Preminger GM. Medical management of stone disease. Curr Opin Urol. 2003;13:229. MEDLINE |
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17. 17Gatorade Sports Science Institute: Formula and nutrition information 2006. 18. 18Goodman JW, Asplin JR, Goldfarb DS. Effect of two sports drinks on urinary lithogenicity. Urol Res. 2009;37:41.
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19. 19Rovell D. First in Thirst: How Gatorade Turned the Science of Sweat Into a Cultural Phenomenon. In: New York: AMACOM; 2006;p. 243. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Correspondence: Department of Urology, The University of Pittsburgh Medical Center, 3471 Fifth Ave., Kaufmann Bldg. Suite 700, Pittsburgh, Pennsylvania 15213 (telephone: 412-692-4100; FAX: 412-692-7939)
Study received institutional review board approval. Supported by the Gatorade Sports Science Institute. For another article on a related topic see page 1201. PII: S0022-5347(09)01160-4 doi:10.1016/j.juro.2009.05.020 © 2009 American Urological Association. Published by Elsevier Inc. All rights reserved. | |
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