Abstract
Background and Purpose
Fluid consumption has been demonstrated to influence kidney stone formation. Studies have shown that consumption of cola may be a risk factor for stone disease, while fluids containing citric acid may attenuate stone activity. Diet was not always controlled in these investigations, however. We undertook a study to determine the impact of three different fluids on urinary stone risk factors.
Subjects and Methods
Six healthy nonstone-forming adults were placed on a standardized metabolic diet and consumed three different types of fluid during three 5-day periods. There was a 2-day washout between each sequence. The three fluids administered during these periods were Le Bleu® water, caffeine-free Diet Coke,® and Fresca® (citrate containing). These two soda preparations were chosen to prevent the known increase in calcium excretion promoted by carbohydrates and caffeine. Twenty-four hour urine specimens were collected on days 4 and 5 of each sequence. The following urinary parameters were measured: Volume, calcium, oxalate, creatinine, uric acid, citrate, sodium, magnesium, phosphorus, sulfate, urea nitrogen, pH, and supersaturation indices. A paired t test was used for statistical analysis.
Results
Urinary volumes were significantly higher and supersaturation of calcium oxalate significantly lower compared with a self-selected dietary regimen. A decrease in uric acid was also seen in the Fresca cohort. There were no statistically significant differences for any of the urinary parameters.
Conclusion
There is no increased risk or benefit to consuming Fresca or caffeine-free Diet Coke compared with Le Bleu bottled water with respect to stone formation.
Introduction
The prevalence of kidney stones in the United States is increasing and is 4.1% among adult women and 6.3% for adult men.1 In addition, recurrence will occur within 10 years of an initial event in approximately 50% of stone formers.2 This certainly impacts the quality of life of those afflicted and promotes economic stress on the health care system of the United States, where it is estimated that 2 billion dollars are spent annually on the diagnosis and treatment of these patients.1 Therefore, effective measures to prevent stone formation benefit patients as well as the health care system.
Dietary measures to prevent kidney stones have been shown to be effective. Borghi and colleagues3 demonstrated that increased fluid consumption decreased the risk of stone recurrence in first-time calcium oxalate stone formers. Increased fluid consumption has also been shown to decrease the risk of incipient stone formation in 3 large epidemiologic cohorts.4,5
There is some debate as to which fluid is the optimal one to consume for stone prevention.6,7 The administration of citrate-containing fluids has been recommended by a number of investigators. Wabner and Pak8 reported that the intake of 1.2 L of orange juice daily had the same beneficial effects as the consumption of 60 mEq of potassium citrate, including an increased citrate excretion. Others have recommended consumption of lemonade to augment citrate excretion. Seltzer and colleagues9 administered 2 L of lemonade daily to hypocitraturic stone formers and reported a 143% increase in citrate excretion. Kang and associates10 and Penniston and colleagues11 performed similar studies and reported 110% and 142 % increases in citrate excretion. In contrast, Koff and colleagues12 and Odvina13 reported that lemonade consumption did not significantly increase citrate excretion. The latter investigator, however, did report a significant increase in citrate excretion with orange juice intake.
Pais14 demonstrated in a small cohort of healthy adult subjects that Fresca® consumption increased citrate excretion a mean of 40%. These persons were consuming self-selected diets. This sugar- and caffeine-free beverage contains potassium citrate and citric acid. It theoretically has the advantage of containing these substances and is devoid of caffeine, which increases calcium excretion, and high-fructose corn syrup present in other soda beverages. Fructose consumption is a risk factor for stone formation, which is attributed to increased oxalate, calcium, and uric acid excretion, and the promotion of insulin resistance.15–21
We performed a study to determine whether the consumption of Fresca augments citrate excretion and to test whether responses were different with the use of Le Bleu® bottled water or caffeine/sugar-free cola as fluid sources. The use of a cola preparation was selected because there is some evidence that such beverages increase stone activity. This study was conducted with the subjects receiving a standardized metabolic diet administered by our General Clinical Research Center (GCRC). This approach was only undertaken in two of the aforementioned studies and is considered the “gold standard” method of assessing metabolic responses to dietary intervention.
Subjects and Methods
After obtaining Institutional Review Board approval, six nonstone-forming healthy adult (two men and four women) volunteers consented to participate in the study. The mean age of the subjects was 28.8 years (range 27–32 years). The mean body mass index was 22 (range 18.4–26.9). The subjects collected two 24-hour urine specimens while consuming a self-selected diet.
Each person was then placed on a standardized metabolic diet prepared in a GCRC kitchen. The subjects were given one of three drinks (caffeine-free Diet Coke,® Fresca or Le Bleu bottled water) to consume solely over a 5-day period. All subjects drank each of the liquids separated by a 2-day washout period, the order of which was randomly assigned to the subjects at the beginning of the study. Liquid volumes were based on the volunteers' lean body weight.
The calcium content was targeted at 1000 mg/2500 kcal; sodium, 3.5 g/2500 kcal; and oxalate content, 150 mg/2500kcal. This oxalate content is within the reported range of normal oxalate intake.22 Diets were adjusted to within 5% of these amounts and with a ratio of calcium to oxalate in each meal >5:1. Each diet contained 15% to 16% protein, 29% to 30% fat, and 54% to 55% carbohydrate. Two 24-hour urine specimens were collected on days 4 and 5 of each study fluid. All subjects completed all arms of the study.
Twenty-four–hour urine samples were analyzed for volume, calcium, oxalate, creatinine, uric acid, citrate, sodium, magnesium, phosphorus, sulfate, pH, and urea nitrogen. All of the assays except pH were performed using a Beckman analyzer as described previously.23 The pH was measured using an electrochemical pH meter. Oxalate was measured using an oxalate oxidase technique.23 The citric acid, oxalate, phosphate, chloride, potassium, sodium, magnesium, and calcium contents of the beverages were measured using ion chromatography as described previously.24 Supersaturation indices for calcium phosphate and calcium oxalate were calculated using the method of Tiselius.25
Statistical analysis was performed using a paired t test. P values of greater than 0.05 were considered statistically significant. Both the self-selected diet and water diet were used as separate controls in the statistical analysis.
Results
All six subjects completed all arms of the study. Table 1 demonstrates the anion, cation, and citric acid contents of the three tested beverages. Table 2 shows the mean urinary parameters for both the self-selected diet and the three different study drinks. There was a statistically significant increase in the volume of urine produced while the subjects were on the controlled metabolic diets (P = 0.009). Uric acid was significantly less during Fresca consumption compared with the self-selected diet phase (P = 0.006). Supersaturation indices for calcium oxalate showed a significant decrease when comparing Le Bleu bottled water, caffeine-free Diet Coke, and Fresca with the self-selected control group (P < 0.05). There was no change for the supersaturation of calcium phosphate.
Table 1.
Caffeine-free Diet Coke® | Fresca® | Le Bleu®Water | |
---|---|---|---|
Oxalate (mg/L) | <1 | <1 | 0 |
Citrate (mg/L) | 150 (10) | 2330 (270) | 0 |
Phosphate (mg/L) | 276 (12) | <1 | <10 |
Chloride (mg/L) | 46 (3) | 73 (16) | <0.1 |
Sodium (mg/L) | 40.6 (2.1) | 33 (12.6) | 20.9 (3.8) |
Magnesium (mg/L) | 3.1 (0.6) | 2.8 (0.7) | 0 |
Potassium (mg/L) | 66.5 (7) | 290 (14) | 0 |
Calcium (mg/L) | 24.6 (0.1) | 11.8 (3.4) | 0 |
Table 2.
Self-selected | Water | Cola | Fresca® | |
---|---|---|---|---|
Volume (mL)a | 1679.1 (817.6) | 2314 (481.9) | 2595.8 (188.8) | 2500 (358.6) |
Sodium (mmol/d) | 167.1 (93.9) | 97.7 (40.5) | 102.3 (39.7) | 108.2 (40.8) |
Potassium (mmol/d) | 73.6 (30.5) | 61.9 (19.0) | 63.5 (15.6) | 63.2 (14.0) |
Calcium (mg/d) | 143.3 (65.2) | 133.7 (60.4) | 143.9 (70.0) | 137.5 (72.1) |
Magnesium (mg/d) | 73.5 (34.8) | 82.3 (16.5) | 91.3 (19.0) | 92.4 (13.6) |
Creatinine (mg/d) | 1540.1 (682.1) | 1383.2 (422.5) | 1488.1 (437.2) | 1417.2 (403.4) |
Citrate (mg/d) | 617.6 (271.5) | 608.2 (305.8) | 620.2 (356.9) | 630.9 (325.3) |
Phosphate (mg/d) | 831.6 (458.0) | 1005.6 (179.9) | 1049.5 (244.5) | 1029.5 (309.9) |
Uric acid (mg/d)b | 641.8 (217.7) | 543.4 (164.5) | 519.5 (239.5) | 516.8 (202.7) |
Urea nitrogen (mg/d) | 10605.4 (4144) | 11336.6 (2525.5) | 11415 (2849.5) | 11184.5 (3192.9) |
Oxalate (mg/d) | 30.9 (10.9) | 25.6 (7.2) | 26.2 (7.5) | 24.4 (6.2) |
pH | 6.11 (0.39) | 5.92 (0.26) | 5.83 (0.25) | 6.06 (0.39) |
AP(CaOx)c | 0.807 (0.305) | 0.448 (0.225) | 0.427 (0.240) | 0.390 (0.221) |
AP (CaP) | 0.958 (1.68) | 0.280 (0.354) | 0.198 (0.274 | 0.463 (0.606) |
Tiselius indices for calcium oxalate (AP[CaOx]) and calcium phosphate (AP[CaP]) are also provided.
Significant increase in the urinary volumes when comparing self-selected diets with the three treatment protocols (P = 0.0009).
Significant decrease in uric acid excretion when comparing Fresca ingestion with the self-selected diet (P = 0.006).
Significant decrease in supersaturation index of calcium oxalate during Le Bleu® bottled water, caffeine-free Diet Coke,® and Fresca regimens compared with self-selected diet (P < 0.05).
Discussion
Our results demonstrated that there were no differences in urinary stone risk parameters between the three fluid regimens. There were significant increases, however, in urinary volume and reductions in the calcium oxalate saturation indices on all three regimens relative to those collected during the self-selected diet. These were most likely because of dietary control and increased fluid consumption during all three regimens.
An increase in citrate excretion did not occur with the consumption of Fresca. This could be because of the citric acid content of this beverage, which we measured to be 2.33 g/L, an amount that is similar to several lemonade preparations but much lower than lemon, lime, grapefruit, or orange juice.25 The form of citrate present in the beverages could also have been influential. The assay used did not discriminate between citric acid and potassium citrate; the latter form is thought to augment citrate excretion while the other does not.13 This is hypothesized to be because of the hydrogen proton present in citric acid negating the benefits of citrate.13 Potassium citrate, which has a different accompanying cation, provides an alkali load whereas citric acid does not because of the hydrogen cation. Alkali load enhances urinary citrate excretion by reducing renal tubular reabsorption and metabolism of citrate. Other organic acids found in fluids, in the presence of potassium, may produce a similar response, however.
Hönow and associates26 placed subjects on a metabolic diet and assessed the impact of consumption of three different fluids (grapefruit juice, apple juice, and orange juice) on urinary parameters. Urine citrate increased and the supersaturation of calcium oxalate decreased from baseline to a similar degree on all three regimens. The potassium content of all three beverages was similar, while the citrate content of grapefruit and orange juice was robust compared with a negligible amount in apple juice. It is feasible that other organic acids present in apple juice combined with an adequate amount of potassium to produce an alkali load similar to that of the other juices.
The lack of deleterious changes in stone risk factors with consumption of caffeine-free Diet Coke is consistent with the epidemiologic findings of Curhan and colleagues.4,6,7 They reported that the intake of sugar- and caffeine-free cola reduced stone risk compared with caffeine- and sugar-containing cola, which increased stone risk. Rodgers reported that consumption of the latter promoted unfavorable changes in urinary stone risk parameters, including increased oxalate excretion, a lowering of urine pH, and an increase in the relative supersaturation indices.27 Weiss and coworkers28 reported that such cola consumption reduced magnesium and citrate excretion and increased oxalate excretion.
One of the proposed mechanisms for increased oxalate excretion is that cola has a high oxalate content.29 We demonstrated, however, using more contemporary and accurate techniques, that the oxalate content of the cola beverage used in this study was low. The latter findings may be because of increased calcium excretion promoted by sucrose, fructose, and caffeine consumption.15–17,30 In addition, as previously stated, fructose consumption is reported to increase oxalate and uric acid excretion as well as promote insulin resistance.18–21,31–33 The latter is associated with a reduction in urinary pH and increased risk of uric acid stone formation.34–36
A limitation of this study is that these responses were not assessed in stone-forming subjects. It is possible that such subjects could have a different response.
Conclusion
This study demonstrates that Fresca does not augment citrate excretion while having no other deleterious effects on stone risk parameters. Similar results were found with caffeine-free Diet Coke and water. This study also demonstrates the importance of controlling other dietary factors in such studies.
Abbreviation Used
- GCRC
General Clinical Research Center
Disclosure Statement
No competing financial interests exist.
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