Following a request from the European Commission to the European Food Safety Authority (EFSA), the Panel on Food Additives and Nutrient Sources added to Food (ANS) has been asked to provide a scientific opinion on the safety of ChromoPrecise® cellular bound chromium yeast added for nutritional purposes as a source of chromium in food supplements and on the bioavailability of chromium from this source.
ChromoPrecise® chromium yeast is a yeast preparation with an enriched trivalent chromium (chromium(III)) content, obtained by culture of Saccharomyces cerevisiae in the presence of chromium(III) chloride. A daily intake of 100 µg chromium (III) is provided in a single tablet Much of the chromium accumulated by the yeast cells from a trivalent source such as chromium chloride, as in the case of ChromoPrecise® chromium yeast, is bound to amino acids and peptides in the cell and hence is present in an organic form. The Panel noted the lack of data on the actual identity of the chromium species contained in chromium-enriched yeast and their toxicokinetic and toxicodynamic behaviour in the body.
Limited information was provided by the applicant on the bioavailability of chromium from ChromoPrecise® chromium yeast. Although there are reports in the literature that chromium from organic sources such as chromium-enriched yeast is more bioavailable than chromium from inorganic chromium compounds such as chromium chloride, in general the available data do not permit a definite conclusion on this issue. Data from a number of clinical studies that have examined effects of supplementation with chromium-enriched yeasts demonstrate that chromium from chromium-enriched yeast is absorbed to some extent and is bioavailable. The Panel concluded that there are limited data on bioavailability in man of chromium from chromium-enriched yeast but bioavailability is potentially up to ten times higher than that of chromium from chromium chloride. The Panel noted that absorption of chromium (III) from inorganic sources and the diet (an uncharacterised combination of inorganic and organic forms) was low (0.5-2% and 0.5-3% respectively).
ChromoPrecise® chromium yeast is of low acute toxicity, with an LD50 in the rat of > 5 000 mg/kg. In a 90-day study in rats, ChromoPrecise® chromium yeast produced mortalities at the highest dose tested of 2 500 mg/kg bw/day, which were attributed by the study authors to misdosing. The Panel agreed with this conclusion. A slight but statistically significant increase in plasma glucose, triglycerides and plasma aspartate aminotransferase (ASAT) was seen in female rats receiving 2 500 mg/kg bw/day of the chromium yeast, in the absence of histopathological findings. The study authors concluded that these changes were not of toxicological importance and that a NOAEL of 2 500 mg/kg bw/day ChromoPrecise® chromium yeast, the highest dose tested, could be identified in this study. The Panel agreed with this conclusion. No evidence of adverse effects of chromium yeasts were seen in other animal studies in which the effects of dietary supplementation with chromium yeast on animal growth, general health and immune function, and in animal models of diabetes have been investigated.
ChromoPrecise® chromium yeast was non-genotoxic in a range of genotoxicity studies, comprising bacterial and mammalian cell mutagenicity assays, a chromosome aberration test and an in vitro micronucleus assay. Data on genotoxicity of other chromium (III) sources indicate that there is no concern for this endpoint.
No information was available on the chronic toxicity or carcinogenicity of ChromoPrecise® chromium yeast in experimental animals or in humans. Data on chronic toxicity and carcinogenicity of other chromium(III) sources indicate that there is no concern for these endpoints. There was also no information on the effects of ChromoPrecise® chromium yeast on reproductive performance or development. Limited data on other chromium yeasts provide no evidence of adverse effects on these endpoints.
No adverse effects have been reported in clinical efficacy trials with chromium yeasts, in which a range of parameters, in addition to assessment of insulin action, glucose tolerance and lipid profile, have been investigated. These trials have involved supplementation at levels from below 20 μg chromium(III)/day up to 1000 μg chromium(III)/day for periods from 2 months to up to 7.8 years in non-diabetic and diabetic subjects.
The toxicological data available on ChromoPrecise® chromium yeast indicating an overall low degree of toxicity is underpinned by the data available on other chromium(III) compounds such as chromium(III) chloride and chromium(III) sulphate. The Panel concluded that given the absence of adverse effects in toxicological studies in animals and in clinical efficacy trials in humans, the use of ChromoPrecise® chromium yeast in food supplements is not of concern, despite the lack of data on the actual nature and identity of the organic chromium compounds contained in the product and the absence of data on chronic toxicity, carcinogenicity, reproductive and developmental toxicity.
The Panel stresses that this conclusion only applies to ChromoPrecise® chromium yeast and not to other chromium-enriched yeasts for which equivalent safety data has not been provided.
Reported average European chromium intakes from the diet range from 61 µg/day in German males to 160 µg/day in an older Swedish study. The 97.5th percentile intake values of chromium were reported as ranging from 126 µg/day in French adults to 170 µg/day in UK adults. The first French total diet study reports average chromium intakes varying from 63 µg/day to 69 µg/day for children aged 3-10 years and 11-17 years, respectively, and high percentile intakes in the range of 107 µg/day to 119 µg/day in the same age classes (Leblanc et al., 2005)
Based on the information provided by the applicant, supplementation with ChromoPrecise® chromium yeast is intended to be in the range of 30-100 µg chromium(III)/day.
In the adult population, assuming a mean and a 97.5th percentile European dietary chromium(III) intake in the range of 60–160 µg/day and 126-170 µg/day, respectively, a consumption of an additional food supplement containing 100 µg chromium(III)/day (the upper level of daily intake of ChromoPrecise® chromium yeast for adults indicated by the applicant) would result in a total daily chromium intake varying between 160 and 260 µg chromium(III)/day in an adult at the average level of dietary exposure and between 226 and 270 µg/day for high consumers.
In children aged 3-17 years, assuming a mean and a 97.5th percentile dietary chromium(III) intake in the range of 63–69 µg/day and 107-119 µg/day (French data), respectively, a consumption of an additional food supplement containing 100 µg chromium(III)/day (the upper level of daily intake of ChromoPrecise® chromium yeast for adults indicated by the applicant) would result in a total daily chromium intake varying between 163 and 169 µg chromium(III)/day in an adult at the average level of dietary exposure and between 207 to 219 µg/day for high consumers.
The Panel noted that these total intakes cannot be compared with a tolerable upper intake level established by e.g. the SCF or the US Food and Nutrition Board (FNB), since such an upper level has not been established, but are below the daily intake of approximately 10 mg/person considered by EVM to be expected to be without adverse health effects. The Panel also noted that the total intakes of chromium for children aged 3-17 years have been based on consumption of the adult supplemental dose of 100 µg chromium(III)/day, which is a worst-case scenario.
The Panel has previously concluded that the intake of chromium(III) from PARNUTS and foods intended for the general population (including food supplements) should not exceed 250 μg/day, the value established by the WHO for supplemental intake of chromium that should not be exceeded. (WHO, 1996). The maximum intended use level of 100 μg chromium(III)/day proposed by the applicant for ChromoPrecise® chromium yeast is below this level. The Panel concluded that ChromoPrecise® chromium yeast as a source of trivalent chromium added for nutritional purposes to PARNUTS and foods intended for the general population (fortified foods and food supplements) would not be of concern provided that the amount of total supplemental intake of chromium does not exceed 250 μg/day
The Panel concluded that the ability of ChromoPrecise® chromium yeast to elicit allergic responses in individuals with yeast sensitivity cannot be ascertained, therefore those individuals with yeast sensitivity should be informed of the presence of yeast protein.
The Panel considered that the specification for chromium(VI) ≤ 0.2 % of total chromium in the product should be maintained.