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Hydroxycitrate: a potential new therapy for calcium urolithiasis

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Abstract

Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.

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Abbreviations

ACO:

Amorphous calcium oxalate

AFM:

Atomic force microscopy

CA:

Citrate

CaP:

Calcium phosphate

CaOx:

Calcium oxalate

COD:

Calcium oxalate dihydrate

COM:

Calcium oxalate monohydrate

COT:

Calcium oxalate trihydrate

FDA:

Food and drug administration

GC:

Garcinia Cambogia

GHS:

Genetic hypercalciuric stone forming

HCA:

Hydroxycitrate

OTC:

Over the counter

Ox:

Oxalate

S:

Supersaturation ratio

ULM:

Upper limit of metastability

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Funding

J.D.R. acknowledges support from the Welch Foundation (grant E-1794).

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Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, 77204, USA

    Doyoung Kim & Jeffrey D. Rimer

  2. Litholink Corporation, Laboratory Corporation of America® Holdings, 2250 W Campbell Park Dr, Chicago, IL, 60612, USA

    John R. Asplin

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  1. Doyoung Kim
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Correspondence to John R. Asplin.

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J.R.A. and J.D.R. have filed patent applications on the use of hydroxycitrate and other modifiers as growth inhibitors of pathological calcification.

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Kim, D., Rimer, J.D. & Asplin, J.R. Hydroxycitrate: a potential new therapy for calcium urolithiasis. Urolithiasis 47, 311–320 (2019). https://doi.org/10.1007/s00240-019-01125-1

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