This week (Aug 21, 2018) a new paper about sucralose appeared in the Journal of Toxicology and Environmental Health. The paper describes a study in which rats were fed sucralose for 40 days. Two new metabolites of sucralose were found, and these metabolites were detected in the fat tissue of the rats two weeks after sucralose was removed from their diet. Many questions come to mind: Did the rats get a dose that is relevant to human exposure? Why weren't these metabolites detected 30 or 40 years ago? Do these newly discovered metabolites have any adverse effect in humans?
Here's how the experiment was done. There were 10 rats (5 male, 5 female). For the first 9 days, they had free access to water and a standard lab rat food. For the next 40 days, the rats also received sucralose once a day by gavage (tube down the throat, directly into the stomach). On average, the rats received 80.4 mg of sucralose per kg of body weight per day. For comparison, the Acceptable Daily Intake (ADI) for sucralose in humans is 5 mg/kg/day in the US, and 15 mg/kg/day in the European Union. So the rats got a higher dose than humans are expected to get, but only by a factor of 5-16 x. Urine and feces were analyzed daily, and at the end of the study, four of the rats were sacrificed and their adipose tissue was analyzed.
Results: Two previously unknown metabolites were discovered in urine and feces. These appear to be acetylation products, which are more fat-soluble and less water-soluble than sucralose. Increased fat-solubility means that the products would be easier for the body to absorb, and these products appear to be so fat-soluble that they accumulate in fat tissue. Why didn't earlier safety studies detect these metabolites? Probably because of a faulty assumption. There are many enzymes involved in metabolizing foreign substances in the body, and most of the time, these enzymes carry out reactions that make the substance more water-soluble, so that they can easily be excreted in the urine. The people looking for metabolites in previous studies extracted the feces with methanol, which would extract sucralose and anything more water-soluble than sucralose. But methanol may not have efficiently extracted the acylated metabolites, or the acylated metabolites may have transfered the acyl group to methanol molecules (transesterification) during the extraction and analysis.
The exact structures of these acylated metabolites are not yet known, and of course we know nothing about the safety of these products. We know that a lot of ingested sucralose is excreted intact, so the amount of acetylated sucralose formed from a single sucralose-sweetened product will be quite small, but if you consume sucralose-sweetened products on a daily basis, how much of these products will accumulate, and what will be their effects? Clearly this is a situation where "more research is needed," but the discovery of these new metabolites, and their accumulation in fat tissue, is a cause for concern.