Re: “Using Low-Calorie Orange Juice as a Dietary Alternative to Alkali Therapy” by Large et al.

In this study, Large et al. explore alternative dietary sources of alkali and citrate given the poor gastrointestinal tolerance and increasing cost of potassium citrate. ¹ The authors performed ion chromatography to assess the alkali content of several commonly consumed citrus beverages. From these analyses, three drinks (Crystal Lite Lemonade, Tropicana50, and Kroger Low Calorie Orange Juice) were selected for further assessment given their high concentrations of alkali (citrate and malate). Ten participants, acting as their own controls, consumed 1 L of the specified drink and 1 L of water each day for 7 days, followed by a 24-hour urine collection. The pH was noted to significantly increase with all drinks/beverages. Although citrate levels rose by >100 mg/day with all drinks, none of these changes were statistically significant.

It has been our experience that many patients face financial and/or compliance challenges with both the traditional pharmacologic alkalization medication (potassium citrate) and alternative therapies (e.g., potassium bicarbonate, sodium bicarbonate). We, therefore, commend the authors on their study to identify a dietary alternative for effective urinary alkalization therapy. As acknowledged by the authors, 60 mEq of generic Urocit-K daily is expensive. Even if utilizing GoodRx.com retail pricing, the cost annually would be ∼$3800. Thus, even in high volumes, a clear financial advantage is conferred by low calorie orange juice or Crystal Lite. However, it is notable that their results are limited by the lack of a standardized metabolic diet during the study to control for other alkali sources and substances that could affect urinary citrate and pH.

This limitation, not withstanding their results, evokes a number of important questions. First, what is the mechanisms by which urinary alkalinization occurred? Specifically, although pH significantly increased, citrate and potassium did not significantly increase, nor did ammonium significantly decrease, as previously demonstrated with orange juice (ref #17). One potential explanation could be that the clinically significant increase in urinary sulfate, perhaps related to a higher intake of animal proteins at baseline, may be contributing to a more acidic urinary environment? Second, is the clinically notable increase in urinary oxalate identified with consumption of both orange juices worrisome? This increase, as compared with potassium citrate, has previously been demonstrated. ² Does this ultimately push the urinary microenvironment into a more lithogenic state or does the improvement in pH outweigh this risk? The consumption of ascorbic acid alone has been shown to increase urinary oxalate levels. ³ This is thought to occur due to increased endogenous hepatic oxalate production from ascorbic acid and not in vitro conversion after urine collection. ⁴ Finally, relative supersaturations and/or supersaturation indices for calcium oxalate, uric acid, and brushite are not provided in the article. These values are important to assess for a potentially lithogenic urinary microenvironment created with such dietary changes.