Hydroxycitrate may have utility in treating stones

Houston-A new laboratory study suggests that a widely available nutritional supplement has potential to become a new treatment for the wide majority of kidney stones. Clinical research is still pending, however, and there are important caveats about the findings.

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The supplement, hydroxycitrate (marketed as garcinia cambogia extract), is best known as a controversial over-the-counter treatment for weight loss. A related supplement, potassium citrate, is used in over-the-counter and prescription forms to prevent kidney stones.

For the study, which was published in Nature (2016; 536:446-50), the authors compared the stone-treating ability of citrate to citrate derivatives.

Dr. Rimer“Citrate was our benchmark since we know how that behaves. We were trying to test other compounds to see if we could do better,” explained co-author Jeffrey Rimer, PhD, associate professor of chemical and biomolecular engineering at the University of Houston.

The authors found that hydroxycitrate, at low concentrations, performs twice as well as citrate at inhibiting the growth of calcium oxalate monohydrate.

“This indicates that hydroxycitrate is more potent,” Dr. Rimer told Urology Times.

The authors also tested the effect of citrate and hydroxycitrate on nucleation of crystals in human urine. On this front, they performed at similar levels.

Next: Garcinia cambogia extract excreted in urine

Garcinia cambogia extract excreted in urine

The authors also gave hydroxycitrate to human subjects in the form of garcinia cambogia extract and found that it is excreted in urine, a requirement for the compound to be able to function as a kidney stone treatment.

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But Dr. Rimer cautioned that the research doesn’t confirm that hydroxycitrate actually dissolves kidney stones.

“I don’t know if that’s really going to be the case,” he said, especially since the research involved a continuous flow of hydroxycitrate. “It doesn’t mimic a scenario you’d have in a kidney, and mimicking those exact conditions will be difficult.”

A new citrate-based kidney stone treatment would be “very welcome,” one urologist told Urology Times.

Dr. Matlaga“We haven’t seen much new in the past couple of decades,” said Brian R. Matlaga, MD, MPH, professor of urology at Johns Hopkins University, Baltimore, who was not involved in the study. “We know that citrate is a potent inhibitor, and anything that may make it work better for us would be very welcome.”

While potassium citrate is a popular preventive treatment, he said, it has weaknesses. The pills tend to be large and difficult to take, he said, and several are required per day.

Also see: Urinary proteome may hold key to stone prevention

“Some patients will self-discontinue them when you have a cumbersome treatment regimen like that. If we can improve the delivery of the medication, that would make citrate better,” Dr. Matlaga said.

Next: “This has some viability if we can move forward to something that can be taken orally"

What’s next? Dr. Rimer said his team is pursuing funding for animal and human studies.

“This has some viability if we can move forward to something that can be taken orally,” he said.

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But there’s no way at this point to know anything about dosage or side effects. While Dr. Rimer and co-author John Asplin, MD, of Litholink Corp. patented the use of hydroxycitrate and other organic acids like citrate analogues as possible drugs for kidney stone disease, Dr. Rimer acknowledged that the existing over-the-counter availability of hydroxycitrate could forestall commercial development.

Still, “If it turns out it works, there would be a lot of satisfaction in making a breakthrough,” Dr. Rimer said.

As for what physicians should do now, Dr. Rimer cautioned that recommending hydroxycitrate is a dicey proposition.

“You can’t make statements about toxicity, and we don’t know what the long-term effects are of using it,” he said. “It would be hard for doctors to prescribe or say anything without that data in hand.”

The side effects of hydroxycitrate-an extract from the rind of the tropical fruit garcinia cambogia-are believed to be mild. While television’s Dr. Oz has promoted its use as a weight-loss supplement, critics say there’s not enough evidence to support its use.

Dr. Rimer holds a patent on peptide-based therapies.

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