Exploration of Foods and Foodomics

Table 2. Summary of experimental studies on alkalinizing salt interventions and acid-base balance in adults.

Ref.	Population	Intervention (dose)	Outcomes measured	Key findings
[25]	Postmenopausal women	Potassium citrate 90 mmoL/day	BMD, urinary calcium	Improved BMD; reduced urinary calcium; neutralized acidity
[32]	Older adults	Potassium citrate 60–90 mmoL/day	BMD, urinary calcium	Maintained BMD; reduced urinary calcium
[26]	Postmenopausal women	Potassium bicarbonate 30–90 mmoL/day	BMD, bone resorption	Preserved BMD; reduced bone turnover
[33]	Older adults	Potassium bicarbonate 30–90 mmoL/day	BMD, bone turnover markers	Lowered calcium excretion; reduced bone resorption
[50]	Postmenopausal women	Potassium bicarbonate 60–120 mmoL/day	Net acid excretion, calcium balance	Decreased acid load; prevented bone demineralization
[51]	Adults with chronic metabolic acidosis (distal renal tubular acidosis)	Alkaline therapy (potassium citrate)	BMD, bone histology	Correction of metabolic acidosis improved bone histology and was associated with preservation and significant improvement of BMD
[52]	Healthy adults	Sodium + potassium bicarbonate (0.55 mmoL/kg BW)	Acid-base balance	Improved acid-base status; reduced dietary acid load
[54]	Adults post-lithotripsy	Potassium citrate 55 mEq/day	Kidney stone recurrence, urinary pH	Reduced acidity; lowered recurrence rate

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BMD: bone mineral density; BW: body weight.

Declarations

Author contributions

MD: Conceptualization, Methodology, Investigation, Data curation, Writing—original draft, Writing—review & editing. GC: Conceptualization, Resources, Writing—review & editing, Supervision. LR: Conceptualization, Data curation, Writing—original draft, Resources, Writing—review & editing, Supervision, Project administration. All authors read and approved the submitted version.

Conflicts of interest

Luca Rastrelli, who is the Associate Editor of Exploration of Foods and Foodomics, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

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Not applicable.

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References

Pirola L, Górecka K, Leandro CG, Balcerczyk A. Nutritional Studies Evaluating Ketogenic Diets as a Treatment for Obesity and Obesity-Associated Morbidities: Underlying Mechanisms and Potential for Clinical Implementation. Endocrines. 2024;5:585–99. [DOI]

Nojek P, Zawół M, Zimonczyk M, Pawlik W, Nowotarska A, Błaszczyński G. Ketogenic diet and metabolic health: A review of its impact on type 2 diabetes and obesity. Analysis of research on the ketogenic diet in the context of treating metabolic disorders. J Educ Health Sport. 2024;71:55923. [DOI]

Casanueva FF, Castellana M, Bellido D, Trimboli P, Castro AI, Sajoux I, et al. Ketogenic diets as treatment of obesity and type 2 diabetes mellitus. Rev Endocr Metab Disord. 2020;21:381–97. [DOI] [PubMed]

Huang J, Yeung AM, Bergenstal RM, Castorino K, Cengiz E, Dhatariya K, et al. Update on Measuring Ketones. J Diabetes Sci Technol. 2024;18:714–26. [DOI] [PubMed] [PMC]

Borowicz-Reutt K, Krawczyk M, Czernia J. Ketogenic Diet in the Treatment of Epilepsy. Nutrients. 2024;16:1258. [DOI] [PubMed] [PMC]

Zhu H, Bi D, Zhang Y, Kong C, Du J, Wu X, et al. Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal Transduct Target Ther. 2022;7:11. [DOI] [PubMed] [PMC]

De Almeida RJR, Jaber F, Rajab R, Zatreh M, Cabandugama P, Bader N. Effects of Ketogenic Diet Intervention on Metabolic Acidosis in Patients with Obesity and Chronic Kidney Disease. Mo Med. 2023;120:451–8. [PubMed] [PMC]

Skartun O, Smith CR, Laupsa-Borge J, Dankel SN. Symptoms during initiation of a ketogenic diet: a scoping review of occurrence rates, mechanisms and relief strategies. Front Nutr. 2025;12:1538266. [DOI] [PubMed] [PMC]

D’Alessandro C, Giannese D, Piccoli GB, Panichi V, Cupisti A. Ketogenic diets in chronic kidney disease patients: a review for skeptics by skeptics. J Nephrol. 2025;38:1541–56. [DOI] [PubMed] [PMC]

10.

Kuykendall NS, Kuykendall JR. Ketones in the Life Sciences – Biochemistry, Metabolism, and Medicinal Significances. In: Karamanos Y, editor. Metabolism Annual Volume 2024. London: IntechOpen; 2024. [DOI]

11.

Marino C, Pagano I, Castaldo G, Grimaldi M, D’Elia M, Santoro A, et al. Supplementing Low-Sodium Bicarbonate–Calcic (Lete)^® Water: Effects in Women on Bone and Systemic Metabolism. Metabolites. 2023;13:1109. [DOI] [PubMed] [PMC]

12.

Nelson AB, Queathem ED, Puchalska P, Crawford PA. Metabolic Messengers: ketone bodies. Nat Metab. 2023;5:2062–74. [DOI] [PubMed]

13.

Aoi W, Marunaka Y. Importance of pH homeostasis in metabolic health and diseases: crucial role of membrane proton transport. Biomed Res Int. 2014;2014:598986. [DOI] [PubMed] [PMC]

14.

McPherson PA, McEneny J. The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress. J Physiol Biochem. 2012;68:141–51. [DOI] [PubMed]

15.

Ward KE, Ramsay J, Vu BJ. A Case of Severe Metabolic Acidosis in the Setting of a Strict Ketogenic Diet. Cureus. 2023;15:e38741. [DOI] [PubMed] [PMC]

16.

Bushinsky DA, Krieger NS. Effects of acid on bone. Kidney Int. 2022;101:1160–70. [DOI] [PubMed] [PMC]

17.

Lu CL, Wu CC, Hou YC, Zheng CM, Lu KC. Bone Health in Chronic Kidney Disease. In: El Miedany Y, editor. New Horizons in Osteoporosis Management. Cham: Springer International Publishing; 2022. pp. 801–26. [DOI]

18.

Crintea IN, Cindrea AC, Mederle OA, Trebuian CI, Timar R. Electrolyte Imbalances and Metabolic Emergencies in Obesity: Mechanisms and Clinical Implications. Diseases. 2025;13:69. [DOI] [PubMed] [PMC]

19.

Joshi S, Shi R, Patel J. Risks of the ketogenic diet in CKD – the con part. Clin Kidney J. 2024;17:sfad274. [DOI] [PubMed] [PMC]

20.

Naude DF. Chronic Sub-Clinical Systemic Metabolic Acidosis – A Review with Implications for Clinical Practice. J Evid Based Integr Med. 2022;27:2515690X221142352. [DOI] [PubMed] [PMC]

21.

Athinarayanan SJ, Roberts CGP, Vangala C, Shetty GK, McKenzie AL, Weimbs T, et al. The case for a ketogenic diet in the management of kidney disease. BMJ Open Diabetes Res Care. 2024;12:e004101. [DOI] [PubMed] [PMC]

22.

Puchalska P, Crawford PA. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metab. 2017;25:262–84. [DOI] [PubMed] [PMC]

23.

Demigné C, Sabboh H, Puel C, Rémésy C, Coxam V. Organic anions and potassium salts in nutrition and metabolism. Nutr Res Rev. 2004;17:249–58. [DOI] [PubMed]

24.

Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6:274–85. [DOI] [PubMed]

25.

Sellmeyer DE, Schloetter M, Sebastian A. Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. J Clin Endocrinol Metab. 2002;87:2008–12. [DOI] [PubMed]

26.

Frassetto LA, Hardcastle AC, Sebastian A, Aucott L, Fraser WD, Reid DM, et al. No evidence that the skeletal non-response to potassium alkali supplements in healthy postmenopausal women depends on blood pressure or sodium chloride intake. Eur J Clin Nutr. 2012;66:1315–22. [DOI] [PubMed]

27.

Casey JR, Grinstein S, Orlowski J. Sensors and regulators of intracellular pH. Nat Rev Mol Cell Biol. 2010;11:50–61. [DOI] [PubMed]

28.

Phillips R, Hanchanale VS, Myatt A, Somani B, Nabi G, Biyani CS. Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev. 2015:CD010057. [DOI] [PubMed] [PMC]

29.

Pardo MR, Garicano Vilar E, San Mauro Martín I, Camina Martín MA. Bioavailability of magnesium food supplements: A systematic review. Nutrition. 2021;89:111294. [DOI] [PubMed]

30.

Bonjour JP. Calcium and phosphate: a duet of ions playing for bone health. J Am Coll Nutr. 2011;30:438S–48S. [DOI] [PubMed]

31.

Souza ACR, Vasconcelos AR, Dias DD, Komoni G, Name JJ. The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review. Nutrients. 2023;15:5127. [DOI] [PubMed] [PMC]

32.

Moseley KF, Weaver CM, Appel L, Sebastian A, Sellmeyer DE. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res. 2013;28:497–504. [DOI] [PubMed] [PMC]

33.

Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C, Rasmussen HM, Dallal GE. Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab. 2009;94:96–102. [DOI] [PubMed] [PMC]

34.

Yuen AWC, Walcutt IA, Sander JW. An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy. Epilepsy Behav. 2017;74:15–21. [DOI] [PubMed]

35.

Prudencio MB, de Lima PA, Murakami DK, Sampaio LPB, Damasceno NRT. Micronutrient supplementation needs more attention in patients with refractory epilepsy under ketogenic diet treatment. Nutrition. 2021;86:111158. [DOI] [PubMed]

36.

Aoi W, Zou X, Xiao JB, Marunaka Y. Body Fluid pH Balance in Metabolic Health and Possible Benefits of Dietary Alkaline Foods. eFood. 2020;1:12–23. [DOI]

37.

Stoots SJM, Kamphuis GM, Geraghty R, Vogt L, Henderickx MMEL, Hameed BMZ, et al. Global Variations in the Mineral Content of Bottled Still and Sparkling Water and a Description of the Possible Impact on Nephrological and Urological Diseases. J Clin Med. 2021;10:2807. [DOI] [PubMed] [PMC]

38.

Arif H. Complications of Chronic Kidney Disease: Electrolyte and Acid-Base Disorders. In: McCauley J, Hamrahian SM, Maarouf OH, editors. Approaches to Chronic Kidney Disease : A Guide for Primary Care Providers and Non-Nephrologists. Cham: Springer International Publishing; 2022. pp. 211–33. [DOI]

39.

Urwin CS, Snow RJ, Condo D, Snipe RMJ, Wadley GD, Convit L, et al. A Comparison of Sodium Citrate and Sodium Bicarbonate Ingestion: Blood Alkalosis and Gastrointestinal Symptoms. Int J Sport Nutr Exerc Metab. 2022;33:1–10. [DOI] [PubMed]

40.

Schenck PA, Chew DJ, Nagode LA, Rosol TJ. Chapter 6 - Disorders of Calcium: Hypercalcemia and Hypocalcemia. In: Dibartola SP, editor. Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice (Third Edition). Saint Louis: W.B. Saunders; 2006. pp. 122–94. [DOI]

41.

Whitmore SP, Gunnerson KJ. Acid-Base and Electrolyte Disorders in Emergency Critical Care. In: Shiber JR, Weingart SD, editors. Emergency Department Critical Care. Cham: Springer International Publishing; 2020. pp. 301–29. [DOI]

42.

Herren CL, Said RR. Preventing Side Effects and Diet Discontinuation. In: Masino SA, editor. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease. Oxford University Press; 2016. pp. 66–74. [DOI]

43.

McMullen MK. Many foods are more acid-forming than acid-alkaline formulas indicate. Nutr Health. 2024;30:419–27. [DOI] [PubMed]

44.

Luzardo ML. Effects of higher dietary acid load: a narrative review with special emphasis in children. Pediatr Nephrol. 2025;40:25–37. [DOI] [PubMed]

45.

Newmaster K, Zhu Z, Bolt E, Chang RJ, Day C, Mhanna A, et al. A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy. Children (Basel). 2022;9:1372. [DOI] [PubMed] [PMC]

46.

Stolwijk NN, Langeveld M, Jacobs BAW, Vogt L, Haverkamp JA, Ferdinandusse S, et al. Recurrent metabolic alkalosis following ketone body treatment of adult mitochondrial trifunctional protein deficiency: A case report. JIMD Rep. 2022;63:407–13. [DOI] [PubMed] [PMC]

47.

Malieckal DA, Ganesan C, Mendez DA, Pao AC. Breaking the Cycle of Recurrent Calcium Stone Disease. Adv Kidney Dis Health. 2023;30:164–76. [DOI] [PubMed] [PMC]

48.

Dai JC, Pearle MS. Diet and Stone Disease in 2022. J Clin Med. 2022;11:4740. [DOI] [PubMed] [PMC]

49.

Skrajnowska D, Bobrowska-Korczak B. The Effects of Diet, Dietary Supplements, Drugs and Exercise on Physical, Diagnostic Values of Urine Characteristics. Nutrients. 2024;16:3141. [DOI] [PubMed] [PMC]

50.

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 Engl J Med. 1994;330:1776–81. [DOI] [PubMed]

51.

Domrongkitchaiporn S, Pongskul C, Sirikulchayanonta V, Stitchantrakul W, Leeprasert V, Ongphiphadhanakul B, et al. Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis. Kidney Int. 2002;62:2160–6. [DOI] [PubMed]

52.

Maurer M, Riesen W, Muser J, Hulter HN, Krapf R. Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol Renal Physiol. 2003;284:F32–40. [DOI] [PubMed]

53.

McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics. 2009;124:e300–4. [DOI] [PubMed] [PMC]

54.

Carvalho M, Erbano BO, Kuwaki EY, Pontes HP, Liu JWTW, Boros LH, et al. Effect of potassium citrate supplement on stone recurrence before or after lithotripsy: systematic review and meta-analysis. Urolithiasis. 2017;45:449–55. [DOI] [PubMed]

55.

Castaldo G, Pagano I, Grimaldi M, Marino C, Molettieri P, Santoro A, et al. Effect of Very-Low-Calorie Ketogenic Diet on Psoriasis Patients: A Nuclear Magnetic Resonance-Based Metabolomic Study. J Proteome Res. 2021;20:1509–21. [DOI] [PubMed] [PMC]

56.

Castaldo G, Marino C, Atteno M, D’Elia M, Pagano I, Grimaldi M, et al. Investigating the Effectiveness of a Carb-Free Oloproteic Diet in Fibromyalgia Treatment. Nutrients. 2024;16:1620. [DOI] [PubMed] [PMC]