Non-nutritive sweeteners (NNSs) have been associated with numerous negative health outcomes, e.g., weight gain, metabolic syndrome, and ischemic stroke. Underlying mechanisms include changes in hormonal responses and the gut microbiome. Whether NNSs cross the blood- cerebrospinal fluid or blood brain barriers is unknown. We aimed to determine whether sucralose, saccharin, acesulfame-K enter the cerebrospinal fluid (CSF). Aspartame was not assessed, because it is immediately metabolized post-ingestion, whereas the other 3 NNSs are stable.


NNSs were measured with liquid chromatography-mass spectrometry in stored CSF and plasma samples from participants of NIH clinical trials of neuroinflammation (n=30) and narcolepsy (n=10). Dietary information was not available.


In 30 of 40 participants, demographic information was available (15 had multiple sclerosis, 15 were healthy volunteers). Eighteen were female, mean age (± SD) was 44.1±14.6 years and BMI 28.5±4.9 kg/m2. NNSs were detectable in 24 of 40 plasma samples (60%). Corresponding CSF samples were positive in 29% (7 of 24). Four additional CSF samples contained NNS while none were detected in plasma. Thus, a total of 11 CSF samples contained NNSs with maximal concentrations of sucralose 2.9 ng/mL, saccharin 18.6 ng/mL, and acesulfame-K 3.2 ng/mL. No differences were found between healthy volunteers and patients.


Sucralose, saccharin and acesulfame-K enter the CSF. Compared to plasma, CSF clearance appears to be delayed. Future studies need to systematically assess the pharmacokinetics of NNSs. More importantly, NNSs’ direct effects on the human brain need to be investigated, especially on appetite regulation.