EFSA’s Panel on Food Additives and Nutrient Sources added to Food (ANS) found the 10 orotic acid cations, required for DNA and RNA synthesis, was potentially hazardous, with one animal study demonstrating a tumour-promoting effect.
“The Panel concludes that in the light of the tumour-promoting effect of orotic acid in animal experimentation, the small margin of safety to this effect from foreseeable exposure, and the absence of any relevant studies on genotoxicity and of any developmental studies, the use of orotate … at the proposed levels of use is of safety concern,” the ANS stated.
The ANS was asked to provide opinion on the safety and bioavailability of magnesium orotate, zinc orotate, calcium orotate, chromium orotate, copper orotate, iron orotate, manganese orotate, potassium orotate, sodium orotate and choline orotate in food supplements.
The safety of the cations themselves, was not considered by the ANS.
It noted that proposed usage levels by the petitioners – Germany-based Pharmorgana and Lyomark and the UK Health Food Manufacturers’ Association (HFMA) – were provided for forms other than choline and sodium came in between 1.8-6206mg/day.
“For consumers who would consume several nutrients with orotates as source, the total anticipated combined exposure would amount over 11g/day,” ANS said.
“Little documentation on the bioavailability of the mineral salts of orotic acid has been submitted, but one study reveals that the bioavailability of zinc from zinc orotate is comparable to that of zinc from another organic source, as well as an inorganic salt,” it said, noting this would likely apply to the bioavailability of the other salts.
“No data were submitted on reproductive and developmental toxicity and only irrelevant data on genotoxicity.”
It highlighted a study that showed tumour formation in rats receiving repeated dosage of orotic acid at levels between 0.5 and two per cent of their total dietary intake.
It thus established a No Observed Adverse Effect Level (NOAEL) of 50mg/kg body weight/day, while the Lowest Observed Effect Level at 100 mg/kg bw/day.
Orotic acid occurs in cow’s milk but at higher levels in goat’s and sheep’s milk and has been found at levels of 15-118 mg/L in infant formula.
The opinion can be found here.