Gut bacteria convert cyclamate into cyclohexylamine
Around 30-40% of people carry gut bacteria that convert cyclamate into cyclohexylamine. This compound is absorbed into the bloodstream and passes through the kidneys. At high doses in animal studies, cyclohexylamine caused testicular atrophy and impaired sperm production. The European Food Safety Authority's acceptable daily intake is set conservatively to keep cyclohexylamine exposure well below the doses that caused these effects in animals. Human evidence at realistic dietary intakes is limited.
Cyclohexylamine, the gut-bacterial metabolite of cyclamate, caused testicular atrophy and reduced sperm motility in rats at doses of 50 mg/kg body weight per day and above.
2000AnimalEFSA Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) - Opinion on cyclamate
EFSA set an ADI of 0-7 mg/kg body weight per day for cyclamate, derived from the cyclohexylamine reproductive no-observed-adverse-effect level in animals with a 100-fold safety factor.
2000RegulatoryEFSA AFC Panel opinion on cyclamate (E952)
Conversion of cyclamate to cyclohexylamine varies substantially between individuals: non-converters excrete essentially none, while high converters may excrete amounts approaching the level at which animal effects were seen at high cyclamate intakes.
1988ObservationalPrice et al., Food and Chemical Toxicology
Cancer: IARC Group 3 (not classifiable)
Early 1970s animal studies raised concern that cyclamate might cause bladder cancer, leading the USA to ban it in 1969. Subsequent research did not confirm that cyclamate alone causes bladder cancer. IARC reviewed the evidence in 1980 and again in 1999 and placed cyclamate in Group 3: not classifiable as to carcinogenicity in humans. Some animal studies found that cyclamate at high doses could promote tumour growth when a known carcinogen was given first, but cyclamate alone did not initiate tumours in the same experiments.
IARC classified cyclamates as Group 3 (not classifiable as to their carcinogenicity to humans) based on inadequate evidence in humans and inadequate evidence in animals that cyclamate alone causes cancer.
1999Regulatory reviewIARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 73
In two rat studies, sodium cyclamate given after a known bladder carcinogen increased tumour incidence in one study and showed only slight enhancement in a second, suggesting co-carcinogenic rather than primary carcinogenic activity.
1999AnimalIARC Monographs, Volume 73 (NCBI Bookshelf NBK402042)
Epidemiological studies in diabetic populations (who used saccharin and cyclamate more than the general population) showed no significant increase in bladder cancer risk attributable to these sweeteners.
1993ObservationalElcock & Morgan, European Journal of Cancer Prevention
USA ban still in place; the EU and UK permit it
The US FDA revoked cyclamate's approval in 1969 after early animal bladder-cancer data. A petition to reinstate it has never been granted. The UK and EU permit cyclamate within specific food categories under an ADI, on the grounds that the weight of evidence does not confirm carcinogenicity and that the cyclohexylamine concern is managed by the dose limit. This regulatory split means cyclamate is one of the few food additives that is legal on UK and EU shelves but absent from US products.
The US FDA banned cyclamate from food use in 1969 following animal study data; Abbott Laboratories submitted a reinstatement petition in 1982 which the FDA had not approved as of 2025.
RegulatoryUS FDA, Regulatory history of cyclamate
Cyclamate (E952) is authorised for use in Great Britain as of 31 December 2020 under assimilated Regulation (EC) No 1333/2008 Annex II.
2025RegulatoryUK FSA Authorised Regulated Food and Feed Products database (data.food.gov.uk)
Gut microbiome variation and individual exposure
Whether cyclamate poses any meaningful risk depends heavily on whether a person converts it to cyclohexylamine in their gut. This conversion is driven by specific bacteria and is highly variable. People who are high converters are exposed to proportionally more cyclohexylamine from the same intake of cyclamate. The ADI was set to protect even high converters within the studied range, but the uncertainty around conversion rates in the general population is acknowledged by regulators.
The proportion of the population who convert cyclamate to cyclohexylamine varies across studies from approximately 25% to 43%, with conversion rates differing substantially between individuals.
2000Regulatory reviewEFSA AFC Panel opinion on cyclamate (E952)