062: The MILK Study: Investigating Pharmacokinetics of Low-calorie Sweeteners in Mother Infant Dyads

Statement of Purpose: Forty-four percent of lactating women in the United States consume beverages containing low-calorie sweeteners (LCS)[1,2], and the prevalence of LCS consumption is increasing[3–5]. This work aimed to measure sucralose and acesulfame-potassium (ace-K) concentrations in maternal plasma, breastmilk and infants’ plasma at prespecified, serial, time-points for 72 hours after maternal consumption of a beverage containing LCS.

Description of Methods & Materials: Forty mothers who were exclusively breastfeeding and between 4 weeks and 6 months postpartum were enrolled, with their infant. Mothers consumed 20 ounces of Ocean Spray Diet Cranberry™, which contains two commonly consumed LCS, ace-K and sucralose. Rich plasma and breast milk samples were collected from the mothers at prespecified time-points based on pharmacokinetic simulations. One blood sample was collected from each infant via heel stick at prespecified intervals following maternal ingestion of the beverage. Sucralose and ace-K concentrations were measured by LC-MS. Plasma and breast milk concentrations were analyzed by standard non-compartmental analysis (NCA) in Pumas v2.0[6,7].

Data & Results: Sucralose and ace-K were detectable in maternal plasma, breast milk, and infants’ plasma. The mean (±SD) sucralose and ace-K plasma AUCs were 880 (±371) μg/L*h and 2,133 (±3775) μg/L*h, with C_max of 96 (±29) μg/L and 393 (±115) μg/L, T_max of 1.7 (±0.4) hours and 1.9 (±0.4), and T_1/2 of 24.7 (±23.8) hours and 4.4 (±4.0) hours respectively. Sucralose breast milk had a 9-fold lower C_max and a 7-fold lower AUC than plasma. Sucralose concentrations in breast milk were not observed in the first hour in 16 subjects; the T_max of breastmilk was 4-fold higher than that of plasma. Conversely, ace-K was immediately detected in breast milk. Breast milk exposure was 2-fold higher than that of plasma, and was highly variable, with an AUC of 5,004 (±10937) μg/L*h. Ace-K in breast milk had a 1.2-fold higher C_max, 2-fold higher T_max and a similar T_1/2 to plasma. Infants’ plasma had detectable levels of both sweeteners with the mean sucralose concentration at 5.0 (±7.1) μg/L (n=25) and ace-K concentration at 9.2 (±14.8) μg/L.

Interpretation, Conclusion or Significance: This study provides evidence that maternal consumption of LCS leads to transfer of LCS into breast milk and subsequently to the infants’ circulation. Ace-K exhibits immediate transfer from plasma to breast milk and has higher concentrations in breast milk than sucralose. While single consumption sucralose concentrations were measurable in only 63% of infants, the long terminal half-life in both plasma and breast milk may lead to high accumulation if sucralose is consumed multiple times a day. Prior research in vitro and in rodent models indicated that maternal consumption of LCS may have adverse effects on the weight and overall health of infants[8–12]; however, the concentrations of LCS required to cause these effects are unknown. By understanding the exposure of maternal plasma, breast milk, and infant plasma to LCS-containing products, we can establish a foundation for further research on effects to infant health and leverage this to inform recommendations regarding LCS consumption during lactation.

Disclosures: ACS has engaged in consulting work on behalf of Abbott. None of the other authors have any conflicts of interest to disclose