Del Carmen Cano García M. et al., 2023: A randomized, double-blind, placebo-controlled clinical trial of the use of hydroxycitric acid adjuvant to shock wave lithotripsy therapy in patients with calcium stones. Stone fragmentation results.

Friday, 08 September 2023

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IBS Granada, Granada, Spain.
San Cecilio University Hospital, Avda. de la Investigación, S/N, 18016, Granada, Spain.
Regional University Hospital, Málaga, Spain.
Virgen del Valme University Hospital, Seville, Spain.
IBS Granada, Granada, Spain.
San Cecilio University Hospital, Avda. de la Investigación, S/N, 18016, Granada, Spain.

Abstract

Our objective was to improve the results of extracorporeal shock waves lithotripsy using hydroxycitric acid (HCA) like adjuvant therapy. Double blind randomized clinical trial using hydroxycitric acid versus placebo (ID NCT05525130). Multicenter study of adjuvant exposure to a food supplement with hydroxycitric acid (HCA), vs. placebo in patients with calcium oxalate and calcium phosphate lithiasis with indication for extracorporeal shock wave lithotripsy (ESWL). 81 patients were included in the study to compare the effect of HCA versus placebo. Stone fragmentation, the main efficacy variable. Other variables analyzed were stone size, Hounsfield Unit Stone and tolerability. Statistical study with SPSS, statistical significance p ≤ 0.05. Eighty-one patients were included, 40 in the intervention group with HCA and 41 in the control group with placebo. The average stone area was 174,36 mm2 (SD: 32,83 mm2) and the average hardness was 1128,11 (SD: 257,65), with no statistically significant differences between groups. Significant statistical differences were obtained in the analysis of the population by intention to treat and by protocol of the main variable, no fragmentation vs. fragmentation where 100% of the patients, who were given ESWL and took HCA, presented fragmentation while 17% of the patients with placebo did not reach fragmentation (p = 0.03). The adjuvant use of HCA in patients for whom ESWL has been indicated, facilitates stone fragmentation in all cases, which is not achieved in up to 17% of the patients who did not use HCA. We recommend the use of HCA in patients prior to shock wave treatment to improve their fragmentation in calcium stones.

Urolithiasis. 2023 May 30;51(1):83. doi: 10.1007/s00240-023-01456-0.PMID: 37249658 Clinical Trial.
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Comments 1

Peter Alken on Friday, 08 September 2023 08:45

I admit that I am not fond of studies which show in a small series a significant effect of an OTC drug or, like in the present study, a food supplement on whatsoever. The pharmaceutical companies will not or cannot finance a typical very expensive multiphase study to prove the effect of the drug. Instead, they sponsor typically small studies with a positive result they can use for advertising. Typically, these are free access papers like the present and the previous one (1) from this group of authors.

This first retrospective case control study (1) showed in a similar setting 41% “fragmentation” in the control group compared to 66,7% in the verum group. The patients had 30-40 days of the drug starting 10 days before SWL. A similar classification into fragmentation or no fragmentation in the present study would generate a positive result of 83% in the placebo group versus 100% in the verum group. Is this the effect of a good placebo :-)? Of course, in the present study the drug was given during a longer time period of 4 weeks before SWL and 6 weeks after SWL. Is that an effect to be expected? The drug contains everything that is known to help in Ca-Oxalate stones: “FagolitosPlus® is a food supplement whose main ingredient is hydroxy citric acid (HCA). HCA has shown an in vitro inhibitory effect on the calcium oxalate monohydrate (OCM) crystals growth, even in highly supersaturated solutions [6]. In addition, both citrate (CA) and HCA show an inhibitory effect on the calcium phosphate crystals growth. HCA results in electrostatic interactions with calcium ions, forming hydrogen bonds with calcium oxalate and calcium phosphate crystals and then inhibiting the nucleation and growth of these crystals. In addition, the product contains pyridoxine (vitamin B6), which has a reducing effect on the production of endogenous oxalate by increasing glyoxalate transamination (oxalate precursor) to glycine [7]. It also contains magnesium, which is not only capable of binding to oxalate in urine preventing from binding with calcium but which can also reduce the intestinal absorption of calcium [8].” More information is presented in a review (2) and in animal experiments (3).

I also admit my doubts that a 4-week drug intake leads to a significant change in stone consistency. Stone growth is a matter of years (4), difficult to believe that a few weeks of therapy will change a rock. Besides from that, I think that the classification of fragmentation used by the authors is difficult to apply reliably. In addition, the examiners who evaluated the X-rays were obviously not blinded to which group the patients belonged.

Peter Alken

This first retrospective case control study (1) showed in a similar setting 41% “fragmentation” in the control group compared to 66,7% in the verum group. The patients had 30-40 days of the drug starting 10 days before SWL. A similar classification into fragmentation or no fragmentation in the present study would generate a positive result of 83% in the placebo group versus 100% in the verum group. Is this the effect of a good placebo :-)? Of course, in the present study the drug was given during a longer time period of 4 weeks before SWL and 6 weeks after SWL. Is that an effect to be expected? The drug contains everything that is known to help in Ca-Oxalate stones:  “FagolitosPlus® is a food supplement whose main ingredient is hydroxy citric acid (HCA). HCA has shown an in vitro inhibitory effect on the calcium oxalate monohydrate (OCM) crystals growth, even in highly supersaturated solutions [6]. In addition, both citrate (CA) and HCA show an inhibitory effect on the calcium phosphate crystals growth. HCA results in electrostatic interactions with calcium ions, forming hydrogen bonds with calcium oxalate and calcium phosphate crystals and then inhibiting the nucleation and growth of these crystals. In addition, the product contains pyridoxine (vitamin B6), which has a reducing effect on the production of endogenous oxalate by increasing glyoxalate transamination (oxalate precursor) to glycine [7]. It also contains magnesium, which is not only capable of binding to oxalate in urine preventing from binding with calcium but which can also reduce the intestinal absorption of calcium [8].” More information is presented in a review (2) and in animal experiments (3).

I also admit my doubts that a 4-week drug intake leads to a significant change in stone consistency. Stone growth is a matter of years (4), difficult to believe that a few weeks of therapy will change a rock. Besides from that, I think that the classification of fragmentation used by the authors is difficult to apply reliably. In addition, the examiners who evaluated the X-rays were obviously not blinded to which group the patients belonged.

Peter Alken

I admit that I am not fond of studies which show in a small series a significant effect of an OTC drug or, like in the present study, a food supplement on whatsoever. The pharmaceutical companies will not or cannot finance a typical very expensive multiphase study to prove the effect of the drug. Instead, they sponsor typically small studies with a positive result they can use for advertising. Typically, these are free access papers like the present and the previous one (1) from this group of authors. This first retrospective case control study (1) showed in a similar setting 41% “fragmentation” in the control group compared to 66,7% in the verum group. The patients had 30-40 days of the drug starting 10 days before SWL. A similar classification into fragmentation or no fragmentation in the present study would generate a positive result of 83% in the placebo group versus 100% in the verum group. Is this the effect of a good placebo :-)? Of course, in the present study the drug was given during a longer time period of 4 weeks before SWL and 6 weeks after SWL. Is that an effect to be expected? The drug contains everything that is known to help in Ca-Oxalate stones: “FagolitosPlus® is a food supplement whose main ingredient is hydroxy citric acid (HCA). HCA has shown an in vitro inhibitory effect on the calcium oxalate monohydrate (OCM) crystals growth, even in highly supersaturated solutions [6]. In addition, both citrate (CA) and HCA show an inhibitory effect on the calcium phosphate crystals growth. HCA results in electrostatic interactions with calcium ions, forming hydrogen bonds with calcium oxalate and calcium phosphate crystals and then inhibiting the nucleation and growth of these crystals. In addition, the product contains pyridoxine (vitamin B6), which has a reducing effect on the production of endogenous oxalate by increasing glyoxalate transamination (oxalate precursor) to glycine [7]. It also contains magnesium, which is not only capable of binding to oxalate in urine preventing from binding with calcium but which can also reduce the intestinal absorption of calcium [8].” More information is presented in a review (2) and in animal experiments (3). I also admit my doubts that a 4-week drug intake leads to a significant change in stone consistency. Stone growth is a matter of years (4), difficult to believe that a few weeks of therapy will change a rock. Besides from that, I think that the classification of fragmentation used by the authors is difficult to apply reliably. In addition, the examiners who evaluated the X-rays were obviously not blinded to which group the patients belonged. Peter Alken

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