Relationship of Creatinine and Nutrition with Arsenic Metabolism: Smith et al. Respond

potentially sparing SAM for methyla tion of other substrates such as As. We are currently testing this hypothesis in a randomized controlled trial of creatine supplementation. In addition, as Basu et al. (2011) noted, and as we have previously reported (Gamble and Liu 2005), one implication of the observed association between uCr and As methylation capacity is that urinary As should not be expressed per gram creatinine to correct for urine concentration. Rather, uCr should be included as a covariate in regression models. One concerning aspect of the study by Basu et al. (2011) is the handling of blood samples used for nutrient measure ments. As noted by Basu et al. and in a previous pub‑ lication on these same participants (Chung et al. 2006), the blood samples were stored in an ice chest in the field for up to 24 hr before processing. This 24‑hr delay can be problematic for some nutrients, especially folate, which is extremely sensitive to oxida‑ tive degrada tion (Drammeh et al. 2008). Basu et al. (2011) reported that in uni variate analy‑ ses, they observed higher urinary percentages of InAs in individuals with higher serum folate concentrations. This finding is contrary to our previous findings that folate facilitates As methylation (ancy might be explained by differences in sample processing. Basu et al. (2011) also reported associa‑ tions between dietary intake of several nutri‑ ents (assessed using a modified 24‑hr recall) and As methylation capacity. One of the most critical and widely discussed issues in nutri‑ tional epidemiology is the method used to adjust for total energy intake (TEI) (Willett et al. 1997). The main reasons to adjust for TEI are to a) adjust for potential confound‑ ing by TEI, b) remove extraneous variation in nutrient intakes that is due only to their correlation with TEI, and c) simulate a dietary intervention. What is often most relevant is diet composition, or nutrient intake in rela‑ tion to TEI (Willett et al. 1997). Several methods are available to adjust for TEI, and the best approach can vary depending on the nutrient and question of interest. Basu et al. (2011) adjusted for TEI by dividing each nutrient intake by TEI (nutrient density method). While this approach is appealing because of its simplicity, in reality it can cre‑ ate a complex variable (Willett and Stampfer 1998). For example, when TEI is related to the outcome of interest, the …