Inclusion Complexes of Litsea cubeba (Lour.) Pers Essential Oil into ß-Cyclodextrin: Preparation, Physicochemical Characterization, Cytotoxicity and Antifungal Activity.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with ß-cyclodextrin (ß-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:ß-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:ß-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into ß-CD was successful, as well as the preliminary biological results, evidencing that the ß-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

Advances in biotin biosynthesis and biotechnological production in microorganisms.

Biotin, also known as vitamin H or B7, acts as a crucial cofactor in the central metabolism processes of fatty acids, amino acids, and carbohydrates. Biotin has important applications in food additives, biomedicine, and other fields. While the ability to synthesize biotin de novo is confined to microorganisms and plants, humans and animals require substantial daily intake, primarily through dietary sources and intestinal microflora. Currently, chemical synthesis stands as the primary method for commercial biotin production, although microbial biotin production offers an environmentally sustainable alternative with promising prospects. This review presents a comprehensive overview of the pathways involved in de novo biotin synthesis in various species of microbes and insights into its regulatory and transport systems. Furthermore, diverse strategies are discussed to improve the biotin production here, including mutation breeding, rational metabolic engineering design, artificial genetic modification, and process optimization. The review also presents the potential strategies for addressing current challenges for industrial-scale bioproduction of biotin in the future. This review is very helpful for exploring efficient and sustainable strategies for large-scale biotin production.

Computational framework for identifying and evaluating mutagenic and xenoestrogenic potential of food additives.

Food additives are chemicals incorporated in food to enhance its flavor, color and prevent spoilage. Some of these are associated with substantial health hazards, including developmental disorders, increase cancer risk, and hormone disruption. Hence, this study aimed to comprehend the in-silico toxicology framework for evaluating mutagenic and xenoestrogenic potential of food additives and their association with breast cancer. A total of 2885 food additives were screened for toxicity based on Threshold of Toxicological Concern (TTC), mutagenicity endpoint prediction, and mutagenic structural alerts/toxicophores identification. Ten food additives were identified as having mutagenic potential based on toxicity screening. Furthermore, Protein-Protein Interaction (PPI) analysis identified ESR1, as a key hub gene in breast cancer. KEGG pathway analysis verified that ESR1 plays a significant role in breast cancer pathogenesis. Additionally, competitive interaction studies of the predicted potential mutagenic food additives with the estrogen receptor-α were evaluated at agonist and antagonist binding sites. Indole, Dichloromethane, Trichloroethylene, Quinoline, 6-methyl quinoline, Ethyl nitrite, and 4-methyl quinoline could act as agonists, and Paraldehyde, Azodicarbonamide, and 2-acetylfuranmay as antagonists. The systematic risk assessment framework reported in this study enables the exploration of mutagenic and xenoestrogenic potential associated with food additives for hazard identification and management.

Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study.

BACKGROUND: Experimental studies have suggested potential detrimental effects of emulsifiers on gut microbiota, inflammation, and metabolic perturbations. We aimed to investigate the associations between exposures to food additive emulsifiers and the risk of type 2 diabetes in a large prospective cohort of French adults. METHODS: We analysed data from 104 139 adults enrolled in the French NutriNet-Santé prospective cohort study from May 1, 2009, to April 26, 2023; 82 456 (79·2%) were female and the mean age was 42·7 years (SD 14·5). Dietary intakes were assessed with three 24 h dietary records collected over three non-consecutive days, every 6 months. Exposure to additive emulsifiers was evaluated through multiple food composition databases and ad-hoc laboratory assays. Associations between cumulative time-dependent exposures to food additive emulsifiers and the risk of type 2 diabetes were characterised with multivariable proportional hazards Cox models adjusted for known risk factors. The NutriNet-Santé study is registered at ClinicalTrials.gov (NCT03335644). FINDINGS: Of 104 139 participants, 1056 were diagnosed with type 2 diabetes during follow-up (mean follow-up duration 6·8 years [SD 3·7]). Intakes of the following emulsifiers were associated with an increased risk of type 2 diabetes: total carrageenans (hazard ratio [HR] 1·03 [95% CI 1·01-1·05] per increment of 100 mg per day, p<0·0001), carrageenans gum (E407; HR 1·03 [1·01-1·05] per increment of 100 mg per day, p<0·0001), tripotassium phosphate (E340; HR 1·15 [1·02-1·31] per increment of 500 mg per day, p=0·023), acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (E472e; HR 1·04 [1·00-1·08] per increment of 100 mg per day, p=0·042), sodium citrate (E331; HR 1·04 [1·01-1·07] per increment of 500 mg per day, p=0·0080), guar gum (E412; HR 1·11 [1·06-1·17] per increment of 500 mg per day, p<0·0001), gum arabic (E414; HR 1·03 [1·01-1·05] per increment of 1000 mg per day, p=0·013), and xanthan gum (E415, HR 1·08 [1·02-1·14] per increment of 500 mg per day, p=0·013). INTERPRETATION: We found direct associations between the risk of type 2 diabetes and exposures to various food additive emulsifiers widely used in industrial foods, in a large prospective cohort of French adults. Further research is needed to prompt re-evaluation of regulations governing the use of additive emulsifiers in the food industry for better consumer protection. FUNDING: European Research Council, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris, and Bettencourt-Schueller Foundation.

Risk assessment of feed components of botanical origin - Approaches taken in the European Union.

In view of a continuous trend in replacing synthetic feed additives and especially flavouring compounds by botanical preparations, different aspects of the safety evaluations of plants and plant-derived preparations and components in feed are discussed. This includes risk assessment approaches developed by the European Food Safety Authority (EFSA) for phytotoxins regarding unintentional exposure of target animals and of consumers to animal derived food via carry-over from feed. Relevant regulatory frameworks for feed additives and feed contaminants in the European Union are summarised and the essentials of existing guidelines used in the safety evaluation of botanicals and their preparations and components in feed are outlined. The examples presented illustrate how the safety of the botanicals, their preparations and components present in feed is assessed. An outlook on possible future developments in risk assessment by applying new in vitro and in silico methodologies is given.

Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model.

Intestinal fibrosis is a long-term complication of inflammatory bowel diseases (IBD). Changes in microbial populations have been linked with the onset of fibrosis and some food additives are known to promote intestinal inflammation facilitating fibrosis induction. In this study, we investigated how polysorbate 80, sucralose, titanium dioxide, sodium nitrite and maltodextrin affect the gut microbiota and the metabolic activity in healthy and IBD donors (patients in remission and with a flare of IBD). The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) with a static (batch) configuration was used to evaluate the effects of food additives on the human intestinal microbiota. Polysorbate 80 and sucralose decreased butyrate-producing bacteria such as Roseburia and Faecalibacterium prausnitzii. Both compounds, also increased bacterial species positively correlated with intestinal inflammation and fibrosis (i.e.: Enterococcus, Veillonella and Mucispirillum schaedleri), especially in donors in remission of IBD. Additionally, polysorbate 80 induced a lower activity of the aryl hydrocarbon receptor (AhR) in the three groups of donors, which can affect the intestinal homeostasis. Maltodextrin, despite increasing short-chain fatty acids production, promoted the growth of Ruminococcus genus, correlated with higher risk of fibrosis, and decreased Oscillospira which is negatively associated with fibrosis. Our findings unveil crucial insights into the potential deleterious effects of polysorbate 80, sucralose and maltodextrin on human gut microbiota in healthy and, to a greater extent, in IBD patients.

The food additive xylitol enhances the butyrate formation by the child gut microbiota developed in a dynamic colonic simulator.

The gut microbiota should be included in the scientific processes of risk assessment of food additives. Xylitol is a sweetener that shows low digestibility and intestinal absorption, implying that a high proportion of consumed xylitol could reach the colonic microbiota. The present study has evaluated the dose-dependent effects of xylitol intake on the composition and the metabolic activity of the child gut-microbiota. The study was conducted in a dynamic simulator of the colonic microbiota (BFBL Gut Simulator) inoculated with a child pooled faecal sample and supplemented three times per day, for 7 days, with increasing xylitol concentrations (1 g/L, 3 g/L and 5 g/L). Sequencing of 16S rRNA gene amplicons and group-specific quantitative PCR indicated a xylitol dose-response effect on the abundance of Lachnospiraceae, particularly the genera Blautia, Anaerostipes and Roseburia. The microbial changes observed with xylitol corresponded with a dose-dependant effect on the butyrate concentration that, in parallel, favoured an increase in epithelial integrity of Caco-2 cells. The study represents a detailed observation of the bacterial taxa that are the main contributors to the metabolism of xylitol by the child gut microbiota and the results could be relevant in the risk assessment re-evaluation of xylitol as a sweetener.

Extraction, purification, structural characteristics, bioactivity and potential applications of polysaccharides from Avena sativa L.: A review.

Avena sativa L. (A. sativa L.), commonly known as oat, is a significant cereal grain crop with excellent edible and medicinal value. Oat polysaccharides (OPs), the major bioactive components of A. sativa L., have received considerable attention due to their beneficial bioactivities. However, the isolation and purification methods of OPs lack innovation, and the structure-activity relationship remains unexplored. This review emphatically summarized recent progress in the extraction and purification methods, structural characteristics, biological activities, structure-to-function associations and the potential application status of OPs. Different materials and isolation methods can result in the differences in the structure and bioactivity of OPs. OPs are mainly composed of various monosaccharide constituents, including glucose, arabinose and mannose, along with galactose, xylose and rhamnose in different molar ratios and types of glycosidic bonds. OPs exhibited a broad molecular weight distribution, ranging from 1.34 × 105 Da to 4.1 × 106 Da. Moreover, structure-activity relationships demonstrated that the monosaccharide composition, molecular weight, linkage types, and chemical modifications are closely related to their multiple bioactivities, including immunomodulatory activity, antioxidant effect, anti-inflammatory activity, antitumor effects etc. This work can provide comprehensive knowledge, update information and promising directions for future exploitation and application of OPs as therapeutic agents and multifunctional food additives.

[Route to the Adoption of Quantitative NMR in the Japanese Pharmacopoeia].

Quantitative NMR (qNMR) is employed to determine the purity of reagents used as standards for HPLC quantification in the Japanese Pharmacopoeia (JP) and has become recognized as a new absolute quantification method in various fields such as pharmaceuticals, foods, and food additives. This report outlines how and why qNMR has been adopted as an official method in the JP and introduces its progression from JP16 to JP18. The results of a survey of companies in the Japan Pharmaceutical Manufacturers' Association regarding how and when to use qNMR from development to manufacturing stages are introduced. The issues involved in the expansion of the use of qNMR in the field of chemical pharmaceuticals in 2017 are discussed and how these were resolved.

[Standardization and Practical Application of Quantitative NMR (qNMR)].

In Japan, quantitative NMR (qNMR) has already been recognized as a standard method for determining the purity of quantitative samples not only in the Japanese Pharmacopoeia and the Japanese Standards and Specifications for Food Additives but also in the Japanese Industrial Standard (JIS K 0138: 2018). However, since there was no consensus on the establishment of a standard method, the international standardization of qNMR was initiated based on a proposal from Japan. After three years of discussion among experts, International Organization for Standardization/Technical Committee on Food (ISO/TC34) published ISO 24583: 2022 "Quantitative nuclear magnetic resonance spectroscopy-Purity determination of organic compounds used for foods and food products-General requirements for 1H-NMR internal standard method." Publication of this standard has resulted in an internationally agreed upon set of requirements for purity determination using qNMR. New technologies emerge from the cycle of basic research, practical use, and standardization, and qNMR is no exception. A novel chromatographic quantification method based on relative molar sensitivity (RMS) is now being put into practical use. The RMS of an analyte with respect to a different reference substance can be determined by using qNMR to accurately determine the molar ratio and then introducing it into the chromatographic system. This method uses the RMS determined by combining qNMR and chromatography instead of the analyte's reference material to determine its content in sample. This method has been adopted in the Japanese Pharmacopoeia, and the development of a general rule in the Japanese Agricultural Standards (JAS) is also under consideration.

Validating Enteroid-Derived Monolayers from Murine Gut Organoids for Toxicological Testing of Inorganic Particles: Proof-of-Concept with Food-Grade Titanium Dioxide.

Human exposure to foodborne inorganic nanoparticles (NPs) is a growing concern. However, identifying potential hazards linked to NP ingestion often requires long-term exposure in animals. Owing these constraints, intestinal organoids are a promising alternative to in vivo experiments; as such, an in vitro approach should enable a rapid and reliable assessment of the effects of ingested chemicals on the gut. However, this remains to be validated for inorganic substances. In our study, a transcriptomic analysis and immunofluorescence staining were performed to compare the effects of food-grade TiO2 (fg-TiO2) on enteroid-derived monolayers (EDMs) from murine intestinal organoids to the known impacts of TiO2 on intestinal epithelium. After their ability to respond to a pro-inflammatory cytokine cocktail was validated, EDMs were exposed to 0, 0.1, 1, or 10 µg fg-TiO2/mL for 24 h. A dose-related increase of the muc2, vilin 1, and chromogranin A gene markers of cell differentiation was observed. In addition, fg-TiO2 induced apoptosis and dose-dependent genotoxicity, while a decreased expression of genes encoding for antimicrobial peptides, and of genes related to tight junction function, was observed. These results validated the use of EDMs as a reliable model for the toxicity testing of foodborne NPs likely to affect the intestinal barrier.

Oral exposure to food grade titanium dioxide (E171) induces intestinal and behavioural alterations in adult mice but limited effects in young mice.

BACKGROUND: Food-grade titanium dioxide (E171), a white colourant widely used in ultra-processed food products, has been banned in the European Union. However, its usage is still permitted in medicines, and in several other countries. The estimated intake of E171 in children is higher than in adults, which led us to hypothesise that E171 induces differential effects depending on age, with adult mice being the most susceptible due to age, despite the lower dose. AIM: To evaluate the effects of oral administration of E171 on intestinal permeability, ileum, and colon histology, and how these effects impact anxious and depressive behaviour in young and adult mice of both sexes. METHODS: Young and adult mice of both sexes C57BL/6 mice received 10 mg/kgbw E171/3 times per week for 3 months. E171 was administered orally in water by pipetting, while control groups only received drinking water, then intestinal permeability, histology and animal behaviour were analysed. RESULTS: E171 showed an amorphous shape, primary particles sized below 1 µm and anatase crystalline structure. Oral administration of E171 disrupted the intestinal permeability in adult male and female mice, but no effects were observed in young mice of both sexes. E171 promoted ileal adenoma formation in half of the adult female population, moreover hyperplastic crypts, and hyperplastic goblet cells at histological level in adult mice of both sexes. The colon presented hyperplastic goblet cells, hyperchromatic nuclei, increased proliferation and DNA damage in adult mice of both sexes. The anxiety and depressive behaviour were only altered in adult mice treated with E171, but no changes were detected in young animals of both sexes. CONCLUSIONS: Adult mice displayed higher susceptibility in all parameters analysed in this study compared to young mice of both sexes.

Improved biocatalytic activity of steapsin lipase in supercritical carbon dioxide medium for the synthesis of benzyl butyrate: A commercially important flavour compound.

Enzymatic synthesis of flavours, fragrances and food additives compounds have great demand and market value. Benzyl butyrate is commercially important flavour and food additive compound having global use around 100 metric tons/year and widely used in various industrial sectors. However, industrial synthesis of food additive benzyl butyrate is carried out by conventional chemical process which demands for the green biobased sustainable synthetic process. The present work reports steapsin catalyzed synthesis of benzyl butyrate for the first time in supercritical carbon dioxide (Sc-CO2) reaction medium. All reaction variables are optimized in details to obtain competent conversion of 99% in Sc-CO2 reaction medium. The developed steapsin catalyzed synthesis in Sc-CO2 medium offered almost four-fold higher conversion to benzyl butyrate than organic (conventional) solvent. The steapsin biocatalyst was effectually recycled up to five reaction cycles in Sc-CO2 medium. Moreover, the developed steapsin catalyzed protocol in Sc-CO2 medium was extended to synthesize different ten industrially significant flavour fragrance compounds that offers 99% conversion and three to five-folds higher conversion than organic medium. Thus, the present steapsin catalyzed protocol offered improved synthesis of various commercially significant flavour compounds in Sc-CO2. medium.

Subatomic structure of orthorhombic thaumatin at 0.89 Å reveals that highly flexible conformations are crucial for thaumatin sweetness.

Thaumatin is a sweet-tasting protein that elicits a sweet taste at a threshold of approximately 50 nM. Structure-sweetness relationships in thaumatin suggest that the basicity of two amino acids residues, Arg82 and Lys67, are particularly responsible for sweetness. Using tetragonal crystals, our structural analysis suggested that flexible sidechain conformations of these two residues play an important role in sweetness. However, in tetragonal crystals, Arg82 is adjacent to symmetry-related residues, and its flexibility is relatively restrained by the crystal packing. To reduce and diminish these symmetry-related effects, orthorhombic crystals were prepared, and their structures were successfully determined at a resolution of 0.89 Å. Within the orthorhombic lattice, two alternative conformations were more clearly visible at Lys67 than in a tetragonal system. Interestingly, for the first time, three alternative conformations at Arg82 were only found in an orthorhombic system. These results suggest the importance of flexible conformations in sweetness determinants. Such subtle structural variations might serve to adjust the complementarity of the electrostatic potentials of sweet receptors, thereby eliciting the potent sweet taste of thaumatin.

Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

BACKGROUND: Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. METHODS AND FINDINGS: This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. CONCLUSIONS: In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Evaluating the Effects of Chronic Oral Exposure to the Food Additive Silicon Dioxide on Oral Tolerance Induction and Food Sensitivities in Mice.

BACKGROUND: The increasing prevalence of food sensitivities has been attributed to changes in gut microenvironment; however, ubiquitous environmental triggers such as inorganic nanoparticles (NPs) used as food additives have not been thoroughly investigated. OBJECTIVES: We explored the impact of the NP-structured food-grade silicon dioxide (fg-SiO2) on intestinal immune response involved in oral tolerance (OT) induction and evaluated the consequences of oral chronic exposure to this food-additive using a mouse model of OT to ovalbumin (OVA) and on gluten immunopathology in mice expressing the celiac disease risk gene, HLA-DQ8. METHODS: Viability, proliferation, and cytokine production of mesenteric lymph node (MLN) cells were evaluated after exposure to fg-SiO2. C57BL/6J mice and a mouse model of OT to OVA were orally exposed to fg-SiO2 or vehicle for 60 d. Fecal lipocalin-2 (Lcn-2), anti-OVA IgG, cytokine production, and immune cell populations were analyzed. Nonobese diabetic (NOD) mice expressing HLA-DQ8 (NOD/DQ8), exposed to fg-SiO2 or vehicle, were immunized with gluten and immunopathology was investigated. RESULTS: MLN cells exposed to fg-SiO2 presented less proliferative T cells and lower secretion of interleukin 10 (IL-10) and transforming growth factor beta (TGF-ß) by T regulatory and CD45+ CD11b+ CD103+ cells compared to control, two factors mediating OT. Mice given fg-SiO2 exhibited intestinal Lcn-2 level and interferon gamma (IFN-γ) secretion, showing inflammation and less production of IL-10 and TGF-ß. These effects were also observed in OVA-tolerized mice exposed to fg-SiO2, in addition to a breakdown of OT and a lower intestinal frequency of T cells. In NOD/DQ8 mice immunized with gluten, the villus-to-crypt ratio was decreased while the CD3+ intraepithelial lymphocyte counts and the Th1 inflammatory response were aggravated after fg-SiO2 treatment. DISCUSSION: Our results suggest that chronic oral exposure to fg-SiO2 blocked oral tolerance induction to OVA, and worsened gluten-induced immunopathology in NOD/DQ8 mice. The results should prompt investigation on the link between SiO2 exposure and food sensitivities in humans. https://doi.org/10.1289/EHP12758.

Oral Excretion Kinetics of Food-Additive Silicon Dioxides and Their Effect on In Vivo Macrophage Activation.

A food additive, silicon dioxide (SiO2) is commonly used in the food industry as an anti-caking agent. The presence of nanoparticles (NPs) in commercial food-grade SiO2 has raised concerns regarding their potential toxicity related to nano size. While recent studies have demonstrated the oral absorption and tissue distribution of food-additive SiO2 particles, limited information is available about their excretion behaviors and potential impact on macrophage activation. In this study, the excretion kinetics of two differently manufactured (fumed and precipitated) SiO2 particles were evaluated following repeated oral administration to rats for 28 d. The excretion fate of their intact particles, decomposed forms, or ionic forms was investigated in feces and urine, respectively. Monocyte uptake, Kupffer cell activation, and cytokine release were assessed after the oral administration of SiO2 particles. Additionally, their intracellular fates were determined in Raw 264.7 cells. The results revealed that the majority of SiO2 particles were not absorbed but directly excreted via feces in intact particle forms. Only a small portion of SiO2 was eliminated via urine, predominantly in the form of bioconverted silicic acid and slightly decomposed ionic forms. SiO2 particles were mainly present in particle forms inside cells, followed by ionic and silicic acid forms, indicating their slow conversion into silicic acid after cellular uptake. No effects of the manufacturing method were observed on excretion and fates. Moreover, no in vivo monocyte uptake, Kupffer cell polarization, or cytokine release were induced by orally administered SiO2 particles. These finding contribute to understanding the oral toxicokinetics of food-additive SiO2 and provide valuable insights into its potential toxicity.

Modified medication use in dysphagia: the effect of thickener on drug bioavailability-a systematic review.

INTRODUCTION: Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson's disease and frailty. Dysphagia affects 30-40% of the population aged over 65 years-old. Adults with dysphagia often experience long-term conditions requiring multiple medications (often > 5) to manage these. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines' solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners' effects on drug bioavailability. METHODOLOGY: We performed a literature search of MEDLINE & EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies. STUDIES INCLUDED: all genders, countries, > 18 years, community and hospital settings. PRISMA guidance was followed. RESULTS: Five hundred seventy results were found, and 23 articles identified following the reference list review. Following an abstract and full-text review, 18 were included. Most articles evaluated thickeners on dissolution profiles in-vitro, with a few investigating in-vivo. Most studies were single-centre prospective studies identifying that thickeners generally affect dissolution rates of medications. Few studies assessed bioavailability or used clinical outcomes. CONCLUSION: Dysphagia and polypharmacy are common in older adults, but little is known about the effects of altering liquid viscosity on the therapeutic effect of most medications. Further larger-scale studies are required to evaluate the therapeutic impact of thickener, on a bigger range of medications, factoring in other variables such as type of thickener, viscosity of thickener and duration of immersion.