Evidence lacking for over-the-counter products for recurrent stones

Brett Johnson, MD

In this interview, Brett Johnson, MD, discusses key takeaways from his American Urological Association (AUA) 2023 Annual Meeting State-of-the-Art Lecture: Over-the-counter remedies for recurrent stone formers: Where is the evidence? Johnson is an assistant professor of urology at the University of Texas Southwestern Medical Center in Dallas, Texas.

Please summarize your 2023 Annual Meeting State-of-the-Art Lecture: Over-the-counter remedies for recurrent stone formers: Where is the evidence?

I started by talking about the mainstay of stone prevention, which is alkali therapy. Basically, potassium citrate is the standard that we've been using for 20 years. The idea is that, by offering an alkali load, it makes a change in the kidney and it increases the amount of urinary citrate, which is an inhibitor of stones, and increases the pH, can help prevent uric acid stones. Now, even though citrate is the inhibitor for stones, it's not that we're ingesting citrate, it's the alkali load. And so I went into the distinction between that, so if you take something with a lot of citric acid, which has the protonated form of citrate, it doesn't necessarily make it into your urine because it's metabolized by the liver. So it's actually the citrate, with an organic cation, like potassium or sodium. That's why sodium bicarbonate also increases urinary citrate, because it's the alkali itself, and not necessarily the citrate.

Prescription alkali therapy is very costly; it has a lot of side effects, and the compliance is very low. One study shows compliance is as low as 13%. And then there are certain people—younger patients, those of lower socioeconomic status—who tend to be more poorly compliant. [The treatment] causes a lot of gastrointestinal side effects. I talked about the distinction between alkali citrate and total citrate. You really need citrate with an organic anion, like potassium, in order to get the citraturic response. I went over the history of these alternative medicines and medical foods, these over-the-counter products. They're basically not regulated. The FDA essentially said, they're not going to regulate over the counter products. This is from the Orphan Drug Act. But it's a big business; it's billions of dollars.

Ryan Hsi [, MD's] group from Vanderbilt prospectively surveyed patients, and pretty much all stone formers are aware of these treatments, and a lot of them are using them. I went over some common products that are out there. Those include Moonstone, LithoLyte, LithoBalance, KSP tablets, and potassium citrate. We analyzed a bunch of these in the lab and measured the actual amount of citrate compared with what the package said. Some are pretty good, and some are not as good. Ultimately, we found Moonstone had the most alkali citrate, but also was the most costly, and potassium citrate had a good source of citrate and was very inexpensive. You can take a little bit more and it's 50 times cheaper than Moonstone. Dr. Hsi's group at Vanderbilt did a similar study, and their results are very similar to ours.

In another study, from Noah Canvasser [, MD], he actually measured urinary citrate in patients. Rather than analyzing what was in the product itself, he gave the product to non–stone-forming patients and then analyzed their urine. That showed increased urinary citrate. He only used LithoLyte and KSP tabs. He showed increase in urinary citrate for both groups that was only statistically significant for patients taking the KSP tabs. But it wasn't really powered for that, so it's kind of a preliminary work. And then I talked about the plant-based extracts. Probably the 2 most recognizable ones are Cystone and chanca piedra. There are really questionable studies about chanca piedra, very inconsistent end points, not reputable journals, no changes in 24-hour urine, questions as to what the actual proposed mechanism is. In theory, it won't help you pass stones, but that's how the studies were. I went over what studies are available and some of the limitations of those studies. Cystone is a pill with a bunch of different extracts in it, and basically, there are no data to support it whatsoever. There was 1 study that didn't show anything.

I also talked about apple cider vinegar, which is a new popular thing; a lot of patients are asking about it. There's no direct evidence to support its use. It does have acetate, which is an anion. But because of the pH of apple cider vinegar, it's mostly in the protonated form and not really paired with an inorganic cation. There's really not much alkalizing potential for it. But there is this pretty comprehensive study that was done in China that looked at vinegar in general, and demonstrated that it essentially changed the way that the kidney regulates acid base balance, and in that way, can increase alkalization. So it's not really from direct alkalization of the medicine, but just by taking this acid for a long period of time, it caused changes in rat kidneys, and basically improved the ability to secrete citrate. There was another human study where they gave vinegar to the patients every day for a year, and followed their urinary citrate. And basically, 75% of the patients had improved urinary citrate after a year. There are these very preliminary data in China that may support vinegar in general. Apple cider vinegar is just a vinegar; it's acetic acid. That's all vinegar is. There are no studies in the US, there are not really any mature data, but there may be a role for a trial in the future.