Body's own metabolite: ordinary exposure context
Fumaric acid is an endogenous compound produced continuously by every human cell as part of normal energy metabolism. Dietary intake from food use adds a small amount on top of what the body makes internally. Because the compound is metabolised through normal pathways, it does not accumulate in tissue under normal dietary exposure.
Fumaric acid is an intermediate of the citric acid (Krebs) cycle and is present in all aerobic organisms, including the human body, where it is continuously synthesised and metabolised.
Regulatory reviewEFSA Panel on Food Additives and Nutrient Sources (ANS)
High-dose animal studies: kidney effects at extreme levels
Rat studies feeding very high doses of fumaric acid, far above any realistic dietary exposure, found kidney changes including nephrocalcinosis (calcium deposits in the kidney). These effects were dose-dependent and were not observed at lower doses more in keeping with food-use levels. Regulatory bodies have used these findings to derive ADI estimates but have not flagged them as a concern at actual food use.
High dietary doses of fumaric acid in long-term rat studies produced nephrocalcinosis and growth retardation; no-observed-adverse-effect levels were established well above typical human dietary exposure from food additives.
AnimalJECFA (Joint FAO/WHO Expert Committee on Food Additives)
Re-evaluation: EFSA called for new data
EFSA issued a call for data on fumaric acid as part of its systematic re-evaluation programme for all previously authorised food additives. This is a routine process required for every approved additive and does not indicate a specific new safety concern. The re-evaluation had not concluded at the time this record was compiled.
EFSA opened a call for data on fumaric acid (E297) and succinic acid (E363) as part of the mandatory re-evaluation programme under Regulation (EU) No 257/2010.
RegulatoryEFSA call for data on re-evaluation of fumaric acid (E297) and succinic acid (E363)
Medical use at much higher doses: a separate context
Fumaric acid esters, particularly dimethyl fumarate, are used as pharmaceutical treatments for psoriasis and multiple sclerosis at doses many times higher than any food additive use. Side effects at therapeutic doses, including flushing and gastrointestinal upset, are not relevant to trace food additive use, but the medical literature sometimes creates confusion between the two contexts.
Dimethyl fumarate (a fumaric acid ester, not fumaric acid itself) is approved as a pharmaceutical for relapsing-remitting multiple sclerosis; side effects at therapeutic doses include flushing and gastrointestinal effects, occurring at exposures far above food-use levels.
RegulatoryEuropean Medicines Agency, dimethyl fumarate product information
