Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead, methylmercury, arsenic) and polychlorinated biphenyls. If true, this assessment would be highly relevant considering the widespread fluoridation of drinking water and the worldwide use of fluoride in oral hygiene products such as toothpaste. To gain a deeper understanding of these assertions, we reviewed the levels of human exposure, as well as results from animal experiments, particularly focusing on developmental toxicity, and the molecular mechanisms by which fluoride can cause adverse effects. Moreover, in vitro studies investigating fluoride in neuronal cells and precursor/stem cells were analyzed, and 23 epidemiological studies published since 2012 were considered. The results show that the margin of exposure (MoE) between no observed adverse effect levels (NOAELs) in animal studies and the current adequate intake (AI) of fluoride (50 µg/kg b.w./day) in humans ranges between 50 and 210, depending on the specific animal experiment used as reference. Even for unusually high fluoride exposure levels, an MoE of at least ten was obtained. Furthermore, concentrations of fluoride in human plasma are much lower than fluoride concentrations, causing effects in cell cultures. In contrast, 21 of 23 recent epidemiological studies report an association between high fluoride exposure and reduced intelligence. The discrepancy between experimental and epidemiological evidence may be reconciled with deficiencies inherent in most of these epidemiological studies on a putative association between fluoride and intelligence, especially with respect to adequate consideration of potential confounding factors, e.g., socioeconomic status, residence, breast feeding, low birth weight, maternal intelligence, and exposure to other neurotoxic chemicals. In conclusion, based on the totality of currently available scientific evidence, the present review does not support the presumption that fluoride should be assessed as a human developmental neurotoxicant at the current exposure levels in Europe.

Background and Purpose: It used to be a common practice in the field of nutritional epidemiology to analyze separate nutrients, foods, or food groups. However, in reality, nutrients and foods are consumed in combination. The introduction of dietary patterns (DP) and their analysis has revolutionized this field, making it possible to take into account the synergistic effects of foods and to account for the complex interaction among nutrients and foods. Three approaches of DP analysis exist: (1) the hypothesis-based approach (based on prior knowledge regarding the current understanding of dietary components and their health relation), (2) the exploratory approach (solely relying on dietary intake data), and (3) the hybrid approach (a combination of both approaches). During the recent past, complementary approaches for DP analysis have emerged both conceptually and methodologically. Method: We have summarized the recent developments that include incorporating the Treelet transformation method as a complementary exploratory approach in a narrative review. Results: Uses, peculiarities, strengths, limitations, and scope of recent developments in DP analysis are outlined. Next, the narrative review gives an overview of the literature that takes into account potential relevant dietary-related factors, specifically the metabolome and the gut microbiome in DP analysis. Then the review deals with the aspect of data processing that is needed prior to DP analysis, particularly when dietary data arise from assessment methods other than the long-established food frequency questionnaire. Lastly, potential opportunities for upcoming DP analysis are summarized in the outlook. Conclusion: Biological factors like the metabolome and the microbiome are crucial to understand diet-disease relationships. Therefore, the inclusion of these factors in DP analysis might provide deeper insights.

Food-based dietary guidelines (FBDGs) are important tools for nutrition policies and public health. FBDGs provide guidelines on healthy food consumption and are based on scientific evidence. In the past, disease prevention and nutrient recommendations dominated the process of establishing FBDGs. However, scientific advances and social developments such as changing lifestyles, interest in personalized health, and concerns about sustainability require a reorientation of the creation of FBDGs to include a wider range of aspects of dietary behavior. The present review evaluates current European FBDGs with regard to the concepts and aspects used in their derivation, and summarizes the major aspects currently discussed to be considered in future establishment or updates of FBDGs. We identified English information on official European FBDGs through an Internet search (FAO, PubMed, Google) and analyzed the aspects used for their derivation. Furthermore, we searched literature databases (PubMed, Google Scholar) for conceptional considerations dealing with FBDGs. A total of 34 out of 53 European countries were identified as having official FBDGs, and for 15 of these, documents with information on the scientific basis could be identified and described. Subsequently, aspects underlying the derivation of current FBDGs and aspects considered in the literature as important for future FBDGs were discussed. Eight aspects were identified: diet-health relations, nutrient supply, energy supply, dietary habits, sustainability, food-borne contaminants, target group segmentation, and individualization. The first 4 have already been widely applied in existing FBDGs; the others have almost never been taken into account. It remains a future challenge to (re)conceptionalize the development of FBDGs, to operationalize the aspects to be incorporated in their derivation, and to convert concepts into systematic approaches. The current review may assist national expert groups and clarifies the options for future development of local FBDGs.

Epidemiologic studies have suggested an inverse association between flavonoids and cardiovascular disease (CVD). However, the results might have been influenced by the use of dietary assessment methods, which are error prone. The aim of this paper was to systematically review and analyse the literature for evidence of associations between polyphenol biomarkers and CVD and mortality risk in observational studies. Eligible studies were identified through PubMed, Web of Science, and reference lists. Multivariable adjusted associations were extracted. Data were log-transformed and pooled using the random effects model. In total, eight studies were included, investigating 16 different polyphenol biomarkers in association with CVD and mortality. Blood and urine were used as biospecimens, and enterolactone, a lignan metabolite, was most often investigated. Three meta-analyses were conducted investigating the association between enterolactone, and all-cause and CVD mortality, and non-fatal myocardial infarction. A 30% and 45% reduced all-cause and CVD mortality risk were revealed at higher enterolactone concentrations. Furthermore, inverse associations were observed between polyphenol biomarkers and all-cause mortality, kaempferol, and acute coronary syndrome. There is evidence to suggest that enterolactone is associated with a lower CVD mortality risk. This emphasises the importance of the role of the microbiota in disease prevention. To strengthen the evidence, more studies are warranted.