Nephrolithiasis is a growing disease, affecting about 1 in 11 people in the United States each year.¹ Oral alkalinizing agents such as potassium citrate and sodium bicarbonate are commonly prescribed medications for patients with recurrent calcium stones, hypocitraturia, uric acid stones, or cystine stones. However, despite efficacy, long-term adherence with such therapy is as low as 13%.² Many insurance formularies may not cover commonly prescribed formulations, and the average monthly cost of medication may be a barrier to adherence for some patients.

Table. pH, Measured Citrate, Citrate as Alkali, and Cost per Unit of Citrate Alkali for Common Over-the-Counter Food Products and Supplements

This has led to the development of many over-the-counter (OTC) supplements and medical food products, which claim to help prevent stone recurrence, primarily through delivery of alkali salts. Based on the United States Orphan Drug Act, the U.S. Food and Drug Administration (FDA) does not approve or regulate the content, strength, quality, and purity of medical foods. Similarly, in the era of social media and targeted marketing, modern patients are more likely to seek medical information and advice from nonprovider sources. The medical food space has exploded in popularity in the social media era and was valued at $12.3 billion in 2015 (expected to surpass $24 billion by 2025).³ Therefore, manufacturers’ claims must be carefully considered by the consumer and provider alike.

One may note that many OTC supplements contain 99 mg or less of potassium (2% of recommended daily allowance). There is a common misconception that this is due to a regulated limit by the FDA. However, this is not the case. Many manufacturers set this limit due to the fact that the FDA considered requiring a warning label for products that contained 100 mg or greater of potassium per serving.⁴ Ultimately, the FDA has not ruled on a limit for potassium in supplements. More modern medical foods and supplements have not perpetuated to this limit.⁵

In an effort to evaluate the content of common OTC alkali products, Dai et al purchased 9 common OTC products in 2 batches 6 months apart. Using a single serving of each product, the actual content of citrate was measured with spectrophotometry. Total citrate as alkali and cost per 10 mEq of alkali was also calculated.⁶ Results can be seen in the Table.

Total citrate per serving and citrate as alkali can vary greatly, and that variance largely depends on the pH of the product. The cations accompanying citrate in alkali supplements are important in the citraturic response; citrate salts contribute to a systemic alkalinization effect, whereas the protonated form of citrate (citric acid) does not result in a significant alkali load.⁷ The more acidic the solution, the greater percentage of citrate exists in the form of citric acid as hydrogen ions replace the positively charged cations. However, compared to other beverages that have been proposed as dietary alkali alternatives, overall these supplements contain higher alkali concentrations than lemonade (6.1-8 mEq/L), but lower concentrations than orange juice (47.9-63.5 mEq/L).⁸

Alkali citrate per serving varied from 2.3 mEq (Horbäach potassium citrate) to 16.2 mEq (Moonstone powder). Moonstone advertised 60 mEq of citrate, which was accurate if all species of citrate and citric acid were counted, but due to the acidic pH of the solution, the amount of alkali is much lower. Moonstone has since changed the promotional materials to better reflect this. LithoLyte (coffee and powder) delivered 6.4-8.4 mEq of alkali citrate per serving, which was very close to the total citrate calculation owing to the alkaline nature of the solution. This did fall short of the advertised citrate content of 10 mEq. However, LithoLyte advertises that their product contains “10 mEq of Total Citrate” but adds in fine print: “or bicarbonate as a citrate equivalent.” This makes our analysis consistent with their reporting. Horbäach potassium citrate was found to have the lowest amount of citrate alkali. This is due to the fact they limited their product to 99 mg of potassium (2.5 mEq) for reasons noted above. NOW potassium citrate had the lowest cost per alkali ($0.04/10 mEq).

A major limitation of the Dai et al study was lack of a measured citraturic response. Canvasser et al performed a prospective crossover study measuring pH and citrate exertion in healthy adults given LithoLyte and KSPtabs.⁹ Patients were randomized to which was taken first and were given a 3-day washout between supplements. Dosage dispensed was 2 packets twice daily (daily total of 40 mEq of alkali) for LithoLyte and 1 tablet KSPtabs twice daily (daily total 30 mEq of alkali). Based on measured amount of citrate alkali from Dai et al, the estimated daily dose of alkali citrate would be 28 mEq for the LithoLyte group and 56 mEq for the KSPtabs group. However, there may be additional alkali in the form of bicarbonate.

What Canvasser et al discovered in this study was a statistically significant rise in urine pH for both LithoLyte (6.46-6.66, P = .028) and KSPtabs (6.46-6.86, P = .037). Urinary citrate increased for both groups but was only significant for the KSPtabs group (597-797 mg/day, P = 0.037). The greater rise in urinary citrate is likely due to the greater daily dose of alkali citrate in the KSPtabs group. Interestingly, there was no change from baseline in the urinary potassium or sodium levels for either product. It is important to note that this cohort was made up of healthy volunteers with normal baseline urinary citrate. The results for hypocitraturic stone formers may differ. Likewise, this study was not powered to demonstrate superiority of one supplement to another. Side effects were noted with both supplements and mild-to-moderate gastrointestinal side effects noted in about 50% of participants. No participants felt the need to stop the supplements early.

While not regulated by the FDA, some OTC alkali products do contain sufficient alkali to generate a clinically citraturic response. However, alkali content of various OTC supplements and food products varies and may differ from advertised values. Further studies are warranted to determine the clinical effectiveness compared to a standard of care pharmacotherapy for the prevention of recurrent stone disease.