Novel foods in the European Union: Scientific requirements and challenges of the risk assessment process by the European Food Safety Authority.

The European Food Safety Authority (EFSA) has been involved in the risk assessment of novel foods since 2003. The implementation of the current novel food regulation in 2018 rendered EFSA the sole entity of the European Union responsible for such safety evaluations. The risk assessment is based on the data submitted by applicants in line with the scientific requirements described in the respective EFSA guidance document. The present work aims to elaborate on the rationale behind the scientific questions raised during the risk assessment of novel foods, with a focus on complex mixtures and whole foods. Novel foods received by EFSA in 2003-2019 were screened and clustered by nature and complexity. The requests for additional or supplementary information raised by EFSA during all risk assessments were analyzed for identifying reoccurring issues. In brief, it is shown that applications concern mainly novel foods derived from plants, microorganisms, fungi, algae, and animals. A plethora of requests relates to the production process, the compositional characterization of the novel food, and the evaluation of the product's toxicological profile. Recurring issues related to specific novel food categories were noted. The heterogeneous nature and the variable complexity of novel foods emphasize the challenge to tailor aspects of the evaluation approach to the characteristics of each individual product. Importantly, the scientific requirements for novel food applications set by EFSA are interrelated, and only a rigorous and cross-cutting approach adopted by the applicants when preparing the respective application dossiers can lead to scientifically sound dossiers. This is the first time that an in-depth analysis of the experience gained by EFSA in the risk assessment of novel foods and of the reasoning behind the most frequent scientific requests by EFSA to applicants is made.

Approaches used to estimate bioavailability when deriving dietary reference values for iron and zinc in adults.

This review aims to describe approaches used to estimate bioavailability when deriving dietary reference values (DRV) for iron and zinc using the factorial approach. Various values have been applied by different expert bodies to convert absorbed iron or zinc into dietary intakes, and these are summarised in this review. The European Food Safety Authority (EFSA) derived zinc requirements from a trivariate saturation response model describing the relationship between zinc absorption and dietary zinc and phytate. The average requirement for men and women was determined as the intercept of the total absorbed zinc needed to meet physiological requirements, calculated according to body weight, with phytate intake levels of 300, 600, 900 and 1200 mg/d, which are representative of mean/median intakes observed in European populations. For iron, the method employed by EFSA was to use whole body iron losses, determined from radioisotope dilution studies, to calculate the quantity of absorbed iron required to maintain null balance. Absorption from the diet was estimated from a probability model based on measures of iron intake and status and physiological requirements for absorbed iron. Average dietary requirements were derived for men and pre- and post-menopausal women. Taking into consideration the complexity of deriving DRV for iron and zinc, mainly due to the limited knowledge on dietary bioavailability, it appears that EFSA has made maximum use of the most relevant up-to-date data to develop novel and transparent DRV for these nutrients.

Safety of pyrroloquinoline quinone disodium salt as a novel food pursuant to Regulation (EC) No 258/97.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on pyrroloquinoline quinone disodium salt (PQQ), trade name BioPQQ™, as a novel food pursuant to Regulation (EC) No 258/97. PQQ is produced by fermentation using Hyphomicrobium denitrificans CK-275 and purification process. PQQ has a minimum purity of 99.0%. The information provided on the composition, specifications, batch-to-batch variability, stability and production process of PQQ is sufficient and does not raise safety concerns. The applicant intends to market PQQ for use in food supplements for healthy adults, except pregnant and lactating women, at a maximum proposed level of consumption of 20 mg/day (corresponding to 0.29 mg/kg bw per day for a 70-kg person). The proposed level of consumption is at least 250 times higher than the estimated background intake of PQQ occurring naturally in foods. Information on the absorption, distribution, metabolism and excretion of PQQ in animals and humans is limited. Considering the no-observed-adverse-effect-level (NOAEL) of 100 mg/kg bw per day from a 90-day repeated dose oral toxicity study with BioPQQ™, and the maximum proposed level of consumption, the Panel concludes that the margin of exposure (of 344) is sufficient. The Panel concludes that the novel food, pyrroloquinoline quinone disodium salt (BioPQQ™), is safe under the intended conditions of use as specified by the applicant.

Meta-Analysis of Potassium Intake and the Risk of Stroke.

BACKGROUND: The possibility that lifestyle factors such as diet, specifically potassium intake, may modify the risk of stroke has been suggested by several observational cohort studies, including some recent reports. We performed a systematic review and meta-analysis of existing studies and assessed the dose-response relation between potassium intake and stroke risk. METHODS AND RESULTS: We reviewed the observational cohort studies addressing the relation between potassium intake, and incidence or mortality of total stroke or stroke subtypes published through August 6, 2016. We carried out a meta-analysis of 16 cohort studies based on the relative risk (RR) of stroke comparing the highest versus lowest intake categories. We also plotted a pooled dose-response curve of RR of stroke according to potassium intake. Analyses were performed with and without adjustment for blood pressure. Relative to the lowest category of potassium intake, the highest category of potassium intake was associated with a 13% reduced risk of stroke (RR=0.87, 95% CI 0.80-0.94) in the blood pressure-adjusted analysis. Summary RRs tended to decrease when original estimates were unadjusted for blood pressure. Analysis for stroke subtypes yielded comparable results. In the spline analysis, the pooled RR was lowest at 90 mmol of potassium daily intake (RRs=0.78, 95% CI 0.70-0.86) in blood pressure-adjusted analysis, and 0.67 (95% CI 0.57-0.78) in unadjusted analysis. CONCLUSIONS: Overall, this dose-response meta-analysis confirms the inverse association between potassium intake and stroke risk, with potassium intake of 90 mmol (≈3500 mg)/day associated with the lowest risk of stroke.

Multi-micronutrient-fortified biscuits decreased the prevalence of anaemia and improved iron status, whereas weekly iron supplementation only improved iron status in Vietnamese school children.

In Vietnam, nutrition interventions do not target school children despite a high prevalence of micronutrient deficiencies. The present randomised, placebo-controlled study evaluated the impact of providing school children (n 403) with daily multiple micronutrient-fortified biscuits (FB) or a weekly Fe supplement (SUP) on anaemia and Fe deficiency. Micronutrient status was assessed by concentrations of Hb, and plasma ferritin (PF), transferrin receptor (TfR), Zn and retinol. After 6 months of intervention, children receiving FB or SUP had a significantly better Fe status when compared with the control children (C), indicated by higher PF (FB: geometric mean 36·9 (95% CI 28·0, 55·4) µg/l; SUP: geometric mean 46·0 (95% CI 33·0, 71·7) µg/l; C: geometric mean 34·4 (95% CI 15·2, 51·2) µg/l; P < 0·001) and lower TfR concentrations (FB: geometric mean 5·7 (95% CI 4·8, 6·52) mg/l; SUP: geometric mean 5·5 (95% CI 4·9, 6·2) mg/l; C: geometric mean 5·9 (95% CI 5·1, 7·1) mg/l; P = 0·007). Consequently, body Fe was higher in children receiving FB (mean 5·6 (sd 2·2) mg/kg body weight) and SUP (mean 6·1 (sd 2·5) mg/kg body weight) compared with the C group (mean 4·2 (sd 3·3) mg/kg body weight, P < 0·001). However, anaemia prevalence was significantly lower only in the FB group (1·0%) compared with the C group (10·4%, P = 0·006), with the SUP group being intermediate (7·4%). Children receiving FB had better weight-for-height Z-scores after the intervention than children receiving the SUP (P = 0·009). Vitamin A deficiency at baseline modified the intervention effect, with higher Hb concentrations in vitamin A-deficient children receiving FB but not in those receiving the SUP. This indicates that vitamin A deficiency is implicated in the high prevalence of anaemia in Vietnamese school children, and that interventions should take other deficiencies besides Fe into account to improve Hb concentrations. Provision of biscuits fortified with multiple micronutrients is effective in reducing anaemia prevalence in school children.