Sodium polystyrene sulfonate (SPSS) is commonly administered for the acute and chronic treatment of hyperkalemia. Its oral intake is complicated by poor compliance due to multifaceted reasons. We therefore analyzed a method of reducing potassium (K) in formula by pretreatment with SPSS. If effective, this would bypass complications of enterally administered SPSS and provide low-K formula. Thirteen formulas and nutritional supplements were pretreated with SPSS to determine if one could bind K and provide formulas with decreased K contents. Using an SPSS concentration of 1 g/l mEq K in the formula, 62 +/- 2.6% (P less than 0.01, mean +/- SEM) of the K was removed in 30 min, while the sodium (Na) concentration was increased by 234 +/- 37% (P less than 0.01). Analysis suggests that the disproportionate increase in Na is due to exchange for calcium (Ca) and magnesium (Mg), interaction with proteins, and Na suspended with SPSS in the formula. Thus, SPSS pretreatment of formula is an effective method of making low-K formula, but the increase in Na exceeds the K reduction. Attention to possible complications of increased Na intake as well as decreased Ca and Mg intake is warranted.