Palatability Preferences of Non-Capsular Potassium Citrate Alternatives in Healthy Non-Stone-Forming Adults

Abstract

Purpose:

Poor adherence to potassium citrate (KCit) therapy due to palatability issues and gastrointestinal side effects presents a significant barrier to effective kidney stone prevention. While liquid and powder alternatives have emerged as potential solutions, comprehensive comparative palatability data remain limited, hampering evidence-based recommendations for clinical practice. This study aimed to evaluate and compare the palatability of four commercially available liquid KCit formulations (Litholyte, Moonstone StoneStopper, KSPTabs, and Bulk Supplements) in healthy non-stone-forming adults.

Material and Methods:

We conducted a blinded swish-and-spit taste-testing study enrolling 63 healthy participants who sampled each liquid KCit formulation in a randomized order. Participants rated each formulation using a validated five-point Likert scale survey assessing overall palatability, mouthfeel, taste intensity, and aftertaste. Swish-and-spit protocol was followed to minimize systemic absorption while allowing thorough taste evaluation.

Results:

Moonstone StoneStopper (cranberry-raspberry flavored) demonstrated superior overall palatability (mean score: 4.3 ± 0.6), followed by KSPTabs (3.2 ± 0.8), Litholyte (2.8 ± 1.1), and Bulk Supplements (1.7 ± 0.7). Mouthfeel and aftertaste scores correlated strongly with overall preference (r = 0.87 and r = 0.82, respectively).

Conclusions:

Flavor-masked formulations consistently outperformed unflavored options across all taste parameters. These findings suggest that flavored liquid alternatives to KCit therapy are preferred in non-stone formers. Further studies in stone-forming populations are warranted to confirm these results, assess gastrointestinal side effects and evaluate long-term adherence.

Keywords

kidney stones liquid supplements nephrolithiasis palatability patient adherence potassium citrate

Introduction

Kidney stone disease represents a significant and growing health burden in the United States and globally. Affecting approximately 10% of Americans during their lifetime, the prevalence has been steadily increasing over recent decades, with recurrence rates exceeding 50% within 5 to 10 years without appropriate preventive therapy.^1,2 This high recurrence rate contributes to substantial health care costs, with annual expenditures estimated at $5.3 billion in the United States alone.³ Beyond economic considerations, kidney stones cause significant patient suffering, leading to emergency department visits and potential surgical interventions.⁴

Hypocitraturia represents a major metabolic risk factor for calcium-based kidney stones, present in 20% to 60% of stone formers.⁵ Citrate serves as a critical inhibitor of calcium stone formation through multiple mechanisms: it complexes with calcium ions in the gut, reducing intestinal calcium uptake; inhibits nucleation, growth, and aggregation of calcium oxalate crystals; and provides alkalinizing effects that reduce calcium oxalate supersaturation.^6,7 Recognition of these protective mechanisms has established potassium citrate (KCit) supplementation as a cornerstone of medical stone prevention in patients with hypocitraturia.⁸

KCit supplementation has demonstrated significant efficacy in preventing stone recurrence, with randomized controlled trials showing 75% to 85% reductions in new stone formation rates among adherent patients.^9,10 Current American Urological Association guidelines strongly recommend KCit as first-line therapy for patients with hypocitraturic calcium nephrolithiasis.¹¹ Despite its proven efficacy, KCit therapy faces substantial adherence challenges. Studies consistently report poor compliance rates ranging from 30% to 60% at 1 year,^12,13 with adherence declining further over extended treatment periods.¹⁴ Poor adherence significantly undermines the real-world effectiveness of an otherwise highly efficacious preventive therapy. Traditional tablet formulations face several challenges: poor palatability, with patients frequently reporting an unpleasant metallic taste, chalky texture, and persistent bitter aftertaste;¹⁵ gastrointestinal (GI) side effects;¹⁶ high pill burden; and dosing complexity.¹⁷ These factors create an urgent need for more tolerable alternatives.

In response to these challenges, several alternative KCit delivery methods have emerged, including liquid concentrates, flavored crystals, effervescent powders, and combination supplements.¹⁸ These alternatives potentially address key limitations of tablet formulations through improved taste profiles, reduced GI irritation, and simplified dosing schemes.¹⁹ However, despite their commercial availability and increasing clinical recommendation, these alternatives lack rigorous comparative palatability assessment. The existing literature demonstrates a critical gap in this area. While multiple studies have compared the bioequivalence and urinary biochemical effects of alternative KCit formulations,^20,21 evaluation of palatability—an important driver of adherence—remains poorly examined. Previous investigations have focused predominantly on efficacy endpoints rather than patient experience metrics, with palatability typically assessed as a secondary outcome using non-standardized measures.²²

This study addresses the need for evidence-based palatability comparisons to guide clinical recommendations and inform future formulation development. We hypothesized that flavored liquid KCit formulations would demonstrate superior palatability compared with unflavored powders. Our primary objective was to systematically evaluate and compare the palatability of four commercially available liquid/powder KCit alternatives in healthy adults using standardized taste assessment metrics. Secondary objectives included identifying specific taste attributes (mouthfeel, intensity, aftertaste) that most strongly correlate with overall drug palatability and comparing the acceptability of different flavor-masking strategies among available formulations.

Methods

We conducted a blinded swish-and-spit taste-testing study with a crossover design. The study was approved by the University of Southern California (USC) Institutional Review Board (IRB approval number: HS-24-00614). The research was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.²³ The study was conducted using departmental resources without external funding.

Studied KCit supplements were selected based on an Amazon Marketplace search on November 13^th, 2024, for “kidney stone supplement,” and the four most reviewed, non-capsule based products were included. The commercially available KCit formulations were Moonstone StoneStopper (MS)-flavored effervescent granules (“Cranberry Raspberry” flavored), 30 mEq KCit per serving; KSPTabs (KSPT)-KCit effervescent tablet (“Very-Berry” flavored), 20 mEq per serving; Litholyte (LL)-unflavored powder delivering 15 mEq KCit per serving; and Bulk Supplements (BS)-unflavored KCit powder, delivering 300 mg (approximately 3 mEq) KCit per serving. Products were stored according to manufacturer specifications.

Samples were prepared according to manufacturer instructions. Each formulation was dissolved or suspended in room-temperature purified water (23°C ± 1°C). Concentrations were standardized to approximate typical single-dose administration but adjusted to provide equivalent ionic strength across samples. A consistent volume of approximately 15 mL was used for each sample, delivered in identical opaque cups. Samples were prepared immediately before the tasting session to prevent degradation or temperature changes. Participants followed a standardized protocol: abstention from food, flavored beverages, tobacco products, and oral hygiene products for 1 hour prior to testing; mouth rinsing with purified water immediately before beginning the session; and for each sample, participants swished the entire 15 mL volume throughout their mouth, expectorated the entire sample into a personal designated container, rated their immediate taste perception, rinsed their mouth thoroughly with purified water, and waited a minute before proceeding to the next sample. The entire procedure was supervised by trained research staff to ensure protocol adherence. The testing sequence was randomized for each participant to minimize order and carryover effects.

Participants included healthy adults aged 18 to 65 years with the ability to provide informed consent and willingness to abstain from food, beverages (except water), tobacco, and oral hygiene products for 1 hour prior to testing. Exclusion criteria encompassed history of kidney stones or urinary tract disorders; current use of KCit or other citrate supplements; pregnancy or breastfeeding; known allergies or sensitivities to any ingredients in the test formulations; current use of medications known to alter taste perception; self-reported taste disorders, xerostomia, or significant oral pathology; medical conditions requiring potassium restriction, such as severe renal impairment or hyperkalemia; and inability to follow the swish-and-spit protocol. Participants were recruited through campus flyers, departmental email listservs, and word-of-mouth referrals at the USC Health Sciences Campus. Participants received a $25 gift card as compensation for their time and possible transportation expenses.

Each participant served as their own control, tasting all four formulations in a randomized sequence determined using a computer-generated block randomization scheme. This design was selected to minimize order effects while allowing direct intraindividual comparisons across all tested products. The study employed a swish-and-spit protocol commonly used in nutritional and pharmaceutical taste evaluations²⁴ to enable thorough oral exposure while minimizing systemic absorption of the active ingredients. Purified water was provided to all participants. Taste testing was conducted on February 27^th, 2025, in a standardized environment at the USC Health Sciences Campus. The temperature-controlled testing area was free from odors, noise, and other potential sensory distractions. Testing sessions were scheduled between 12:00 PM and 2:00 PM, thus avoiding circadian variation in taste perception.

Taste evaluation employed a validated palatability assessment instrument adapted from previous pharmaceutical taste studies,^25,26 featuring five-point Likert scales for key taste attributes. These included overall palatability (“Rate the taste of the drug product”—from very unpleasant [1] to very pleasant [5]); mouthfeel (“Rate the oral sensation/mouthfeel of the drug product”—from very unpleasant [1] to very pleasant [5]); taste intensity (“How strong is the taste?”—from no taste [1] to very strong [5]); aftertaste (“Rate the aftertaste of the drug product”—from very unpleasant [1] to very pleasant [5]); and aftertaste intensity (“How strong is the aftertaste?”—from no taste [1] to very strong [5]). Participants were actively monitored for adverse events during testing sessions.

A priori power analysis indicated that a minimum of 52 participants was required to detect a 1.5-point difference on a five-point Likert scale with 80% power and a significance level of α = 0.05. All analyses were performed using SPSS Statistics version 28.0 (IBM Corp., Armonk, NY), with p < 0.05 considered statistically significant. Primary analysis involved comparing within-subject Likert scale ratings across formulations using repeated-measures analysis of variance. Post hoc pairwise comparisons were conducted using the Bonferroni correction to control for multiple comparisons. Mean responses and their 95% confidence intervals were measured. Complete data were available for all participants, as the on-site completion protocol effectively prevented missing responses. In the rare instances of ambiguous markings, participants were asked to clarify their responses immediately.

Results

A total of 63 healthy adult participants completed the study. There was a 100% survey completion rate.

Overall taste scores

There was a statistically significant difference in overall taste scores across the four formulations (F[2.42, 150.7] = 86.4, p < 0.001, Greenhouse-Geisser corrected). MS cranberry raspberry flavored received the highest mean palatability score of 4.3 ± 0.6 on a five-point Likert scale. This was followed by KSPT, Very Berry flavored effervescent tablet formulation, with a mean score of 3.2 ± 0.8. LL, unflavored, was rated at 2.8 ± 1.1. BS, unflavored, received the lowest score of 1.7 ± 0.7.

Post hoc pairwise comparisons using the Bonferroni correction confirmed that all pairwise differences between formulations were statistically significant (p < 0.05), apart from LL vs KSPT, which showed a narrower margin and approached but did not reach statistical significance. Overall taste results are shown in Figure 1 and Table 1.

FIG. 1.

Taste response point-range plot.

Table 1.

Taste Response Analysis

Post hoc comparisons‐taste
Comparison
Taste	Taste	Mean difference	SE	df	t	P_bonferroni
LL	- MS	−1.540	0.134	62.0	−11.53	<.001
	- KSPT	−0.778	0.156	62.0	−4.99	<.001
	- BS	−0.381	0.138	62.0	−2.75	0.047
MS	- KSPT	0.762	0.150	62.0	5.09	<.001
	- BS	1.159	0.149	62.0	7.79	<.001
KSPT	- BS	0.397	0.148	62.0	2.69	0.055

Taste intensity

Significant variation in taste intensity was observed between formulations (F[2.49, 154.5] = 61.3, p < 0.001). MS was perceived as having the strongest flavor (4.2 ± 0.5), followed closely by KSPT (3.9 ± 0.6). LL (2.3 ± 0.8) and BS (1.6 ± 0.6) were rated significantly lower in flavor strength, consistent with their lack of added flavoring or effervescence. Despite the stronger flavor intensity of MS and KSPT, their high palatability ratings suggest that flavor strength was not aversive but rather beneficial when balanced by effective flavor masking. Taste intensity results are shown in Figure 2 and Table 2.

FIG. 2.

Taste strength response point-range plot.

Table 2.

Taste Strength Response Analysis

Post hoc Comparisons-Taste strength
Comparison
Taste strength	Taste strength	Mean difference	SE	df	t	P_bonferroni
LL	- MS	−1.540	0.155	62.0	−9.94	<.001
	- KSPT	−0.730	0.143	62.0	−5.09	<.001
	- BS	0.302	0.155	62.0	1.95	0.333
MS	- KSPT	0.810	0.117	62.0	6.90	<.001
	- BS	1.841	0.149	62.0	12.38	<.001
KSPT	- BS	1.032	0.134	62.0	7.71	<.001

Mouthfeel

A significant main effect of formulation was observed for mouthfeel ratings (F[2.64, 164.0] = 47.9, p < 0.001). MS was again rated highest, with a mean mouthfeel score of 4.2 ± 0.6. KSPT received a mean score of 3.4 ± 0.7, LL scored 2.7 ± 1.0, and BS rated lowest with a score of 1.9 ± 0.8. All pairwise differences were statistically significant (p < 0.01), highlighting the strong negative impact of unflavored or gritty textures on participant experience. Mouthfeel results are shown in Figure 3 and Table 3.

FIG. 3.

Oral sensation/mouthfeel response point-range plot.

Table 3.

Oral sensation/mouthfeel response analysis

Post hoc Comparisons-Oral sensation/mouthfeel
Comparison
Oral sensation/mouthfeel	Oral sensation/mouthfeel	Mean difference	SE	df	t	P_bonferroni
LL	- MS	−1.238	0.143	62.0	−8.68	<.001
	- KSPT	−0.762	0.155	62.0	−4.93	<.001
	- BS	−0.286	0.133	62.0	−2.15	0.212
MS	- KSPT	0.476	0.128	62.0	3.73	0.003
	- BS	0.952	0.127	62.0	7.51	<.001
KSPT	- BS	0.476	0.134	62.0	3.56	0.004

Aftertaste and aftertaste intensity

Aftertaste ratings revealed a consistent pattern of favorability toward flavored formulations (F[2.51, 156.6] = 70.1, p < 0.001). MS scored highest at 4.1 ± 0.7, indicating a pleasant and non-lingering aftertaste. KSPT followed at 3.2 ± 0.9. LL and BS were poorly rated with mean scores of 2.5 ± 1.1 and 1.6 ± 0.7, respectively. Aftertaste intensity was also formulation-dependent (F[2.38, 147.6] = 53.4, p < 0.001). Although MS and KSPT had more pronounced aftertaste intensity (4.1 ± 0.6 and 3.7 ± 0.8, respectively), their aftertastes were described as pleasant, whereas BS and LL had weaker but more negatively perceived aftertastes. Aftertaste results are shown in Figure 4 and Table 4. Aftertaste intensity results are shown in Figure 5 and Table 5.

FIG. 4.

Aftertaste response point-range plot.

Table 4.

Aftertaste Response Analysis

Post hoc Comparisons-Aftertaste
Comparison
Aftertaste	Aftertaste	Mean difference	SE	df	t	P_bonferroni
LL	- MS	−0.889	0.143	62.0	−6.20	<.001
	- KSPT	−0.508	0.148	62.0	−3.43	0.007
	- BS	−0.238	0.112	62.0	−2.12	0.230
MS	- KSPT	0.381	0.140	62.0	2.72	0.051
	- BS	0.651	0.143	62.0	4.54	<.001
KSPT	- BS	0.270	0.143	62.0	1.88	0.388

FIG. 5.

Aftertaste strength response point-range plot.

Table 5.

Aftertaste Strength Response Analysis

Post hoc Comparisons-Aftertaste strength
Comparison
Aftertaste strength	Aftertaste strength	Mean difference	SE	df	t	P_bonferroni
LL	- MS	−1.000	0.165	62.0	−6.07	<.001
	- KSPT	−0.587	0.151	62.0	−3.88	0.002
	- BS	0.365	0.107	62.0	3.42	0.007
MS	- KSPT	0.413	0.148	62.0	2.79	0.042
	- BS	1.365	0.120	62.0	11.34	<.001
KSPT	- BS	0.952	0.127	62.0	7.51	<.001

Discussion

This study represents the first academic comparative evaluation of palatability across commercially available non-capsule KCit formulations. Our findings demonstrate substantial and statistically significant differences in palatability metrics, with the flavored effervescent formulations (MS followed by KSP Tabs) consistently outperforming unflavored alternatives across all palatability parameters. The dramatic differences in palatability between flavored and unflavored formulations—with Moonstone, for example, receiving scores more than twice as high as BS on multiple parameters—highlight the role of taste-masking in improving the acceptability of KCit supplements.

Our results build on the foundation of evidence from previous studies suggesting palatability challenges with traditional KCit formulations. Mechlin et al.²⁷reported consistently poor taste scores for Polycitra-K oral solution with subjects reporting a mean taste rating of 5.75 out 10 with a 5 on the scale representing, “Tastes bad. The taste might prohibit me from taking medication.” Similarly, Robinson et al. found that palatability accounted for approximately 28% of observed discontinuations of KCit tablet therapy.¹⁶ Pinheiro et al.²⁸ noted qualitative patient complaints about metallic taste and aftertaste with various citrate preparations, consistent with our quantitative findings for unflavored formulations.

The temporal pattern of discontinuation provides important insights into the relative contributions of palatability vs GI tolerability to overall adherence challenges. Studies by Whalley et al. and Lojanapiwat et al. suggest that GI-related discontinuation tends to occur later in treatment (weeks to months), while taste-related discontinuation often occurs within the first few doses.^12,17 This temporal pattern suggests that while palatability may be the initial barrier to adherence, sustained compliance likely relies more heavily on GI tolerability. Understanding this distinction is crucial for developing comprehensive strategies to improve long-term adherence to KCit therapy.

Compliance with KCit therapy remains a significant challenge in clinical practice, with studies consistently reporting adherence rates of only 30% to 60% at 1 year.^12,13 This suboptimal compliance directly undermines the demonstrated efficacy of KCit, which has shown 75% to 85% reductions in stone recurrence among adherent patients.^9,10 Poor palatability represents a major barrier to adherence, with Robinson et al. reporting that up to 28% of patients discontinue therapy specifically due to taste-related complaints.¹⁶ This evidence suggests that taste optimization is not merely a matter of patient comfort but represents a crucial determinant of therapeutic effectiveness in stone prevention.

Our results suggest that flavored, effervescent formulations may significantly improve the patient experience. Given that adherence remains the principal limitation in KCit therapy effectiveness, this finding may have clinical relevance. Palatability may be considered alongside other factors impacting patient preferences like cost, dose frequency, ease of use, and brand loyalty. Flavored formulations typically carry higher per-dose costs than generic tablets or bulk powders; therefore, further studies on adherence may yield clinically relevant outcomes in preventing stone recurrence.^23,29 Economic modeling incorporating our palatability data could inform cost-effectiveness analyses.

Our findings offer valuable insights for pharmaceutical developers working on improved citrate formulations. Further research comparing multiple flavor options could refine formulation approaches. The superior performance of effervescent granules compared with simple powders or dissolved tablets highlights the importance of the delivery system itself, beyond active ingredients.

Several limitations should be considered when interpreting our findings. This initial study of healthy volunteers limits the generalizability to the clinical target population. Stone formers’ prior experience with citrate products or heightened motivation for treatment might influence palatability perceptions. However, our approach eliminated potential bias from previous citrate exposure. Our study design prioritized palatability assessment over clinical equivalency by using volume-standardized (15 mL) samples rather than equivalent therapeutic doses. The formulations contained different amounts of KCit per serving: MS (30 mEq), KSPT (20 mEq), LL (15 mEq), and BS (∼3 mEq). In clinical practice, patients would adjust volumes or servings to achieve prescribed mEq dosing, making our volume-standardized approach relevant for taste assessment at typical consumption volumes. However, future studies should consider palatability assessment at equivalent therapeutic doses to provide more clinically applicable comparisons.

Our study evaluated immediate taste perception rather than long-term tolerability with repeated use. The swish-and-spit approach does not fully replicate normal consumption experience and disallowed ingestion-induced GI upset in participants, a common complaint among supplementing stone formers.³⁰ While our study did not employ strict isolation protocols typical of monadic testing, participants were tested in a controlled environment free from odors and distractions, with standardized timing (12:00–2:00 PM) to minimize circadian variation. Our randomized crossover design with blinded samples should have minimized bias from other subjects, though complete isolation would have strengthened the methodology. In addition, palatability issues may evolve with continued exposure, either through habituation or cumulative aversion, which was beyond the scope of this investigation. Lastly, we evaluated only four commercially available formulations. Other products, including prescription liquid formulations, other flavor options, and international options, might offer different palatability profiles. We also did not compare palatability of these products against KCit tablets, which represent the standard prescription option for kidney stone patients.

Future studies should address several important research gaps identified by this work. Studies combining palatability assessment, adherence measurement, and urinary citrate and pH measurements would provide a more complete picture, as improved compliance with an agent is only clinically relevant if it induces its intended biochemical effect. Bioequivalence studies comparing these alternative formulations to standard prescription KCit would strengthen the evidence base for clinical decision-making.

This study generates several important avenues for future investigation. Studies directly measuring palatability perceptions among stone-forming patients prescribed different formulations and adherence assessments would provide valuable clinical validation of our findings. Planned studies in stone-forming populations with ingestion protocols will allow a more complete evaluation of the interaction between palatability and GI upset with long-term adherence. Longitudinal assessment of taste fatigue and continued palatability with prolonged use of various formulations would address limitations of our acute testing paradigm. Cost-effectiveness studies incorporating both formulation costs and projected adherence differences could provide valuable health care system perspectives on formulation selection as well.

Conclusion

This palatability assessment of non-capsular KCit formulations reveals significant differences in taste acceptability, with berry flavored effervescent formulations (MS followed by KSP Tabs) consistently outperforming unflavored alternatives across all taste parameters. While validation in stone-forming populations is warranted, our results provide new valuable information on palatability that may be used to improve patient adherence and inform future studies in this area.

Authors’ Contributions

J.S.H.: Conceptualization, methodology, investigation, formal analysis, writing—original draft, and writing—review and editing; B.M.H.: Investigation, data curation, formal analysis, and writing—review and editing; T.H.B.: Methodology and writing—review and editing; M.M.N.: Conceptualization, methodology, supervision, project administration, funding acquisition, writing—review and editing, and senior authorship.

Footnotes

Author Disclosure Statement

J.S.H., B.M.H., T.H.B., and M.M.N.: The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding Information

This research was conducted using departmental resources from the USC Institute of Urology and Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California. No external funding was received for this study.

Abbreviations

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