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Sugar alcohols are widely used as food additives and drug excipients. Erythritol (INS 968) is an important four-carbon sugar alcohol in the food industry. Erythritol occurs naturally in certain fruits, vegetables, and fermented foods. Currently, HPLC and GC methods are in use for the quantification of erythritol in natural/processed foods. However,...
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... developed by making use of specific antibodies to meso- erythritol should serve as a sensitive analytical tool to detect and quantitate nanogram amounts of meso-erythritol in various biological samples, natural/processed foods, and pharmaceuticals containing erythritol as an excipient. The erythritol content of some natural and processed foods is listed in Table 1. In this paper, an immunoassay has been described for erythritol, and the method has been validated using a natural food (watermelon; Citrullus lanatus) and a processed food (red wine). ...
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Citations
... The sugar alcohol erythritol is naturally occurring in some fruits such as grapes, melons, pears and fermented products like soy sauce, red wine and cheese (1). In addition, erythritol is an endogenously occurring polyol (2). ...
... Interestingly, endogenous erythritol synthesis is also elevated in response to oxidative stress (6). It is known that the pentose-phosphate pathway is more active in subjects with preexisting cardiovascular disease (1,7). This could therefore explain the elevated erythritol concentrations measured in the cohorts, without consumption via food being a factor. ...
... Erythritol and xylitol were positively associated with 8-iso-PGF2a and 8-OHdG, respectively; they are sugar alcohols that occur naturally in fruits, vegetables and fermented foods (only erythritol) (Bond and Dunning, 2006;Sreenath and Venkatesh, 2016). Moreover, erythritol and D-xylitol are used as sweeteners and have potential antihyperglycemic properties (Wölnerhanssen et al., 2020). ...
Background
Exposure to pesticides has been associated with oxidative stress in animals and humans. Previously, we showed that an organic food intervention reduced pesticide exposure and oxidative damage (OD) biomarkers over time; however associated metabolic changes are not fully understood yet.
Objectives
We assessed perturbations of the urine metabolome in response to an organic food intervention for children and its association with pesticides biomarkers [3-phenoxybenzoic acid (3-PBA) and 6-chloronicotinic acid (6-CN)]. We also evaluated the molecular signatures of metabolites associated with biomarkers of OD (8-iso-PGF2a and 8-OHdG) and related biological pathways.
Methods
We used data from the ORGANIKO LIFE + trial (NCT02998203), a cluster-randomized cross-over trial conducted among primary school children in Cyprus. Participants (n = 149) were asked to follow an organic food intervention for 40 days and their usual food habits for another 40 days, providing up to six first morning urine samples (>850 samples in total). Untargeted GC–MS metabolomics analysis was performed. Metabolites with RSD ≤ 20% and D-ratio ≤ 50% were retained for analysis. Associations were examined using mixed-effect regression models and corrected for false-discovery rate of 0.05. Pathway analysis followed.
Results
Following strict quality checks, 156 features remained out of a total of 610. D-glucose was associated with the organic food intervention (β = −0.23, 95% CI: −0.37,−0.10), aminomalonic acid showed a time-dependent increase during the intervention period (βint = 0.012; 95% CI:0.002, 0.022) and was associated with the two OD biomarkers (β = −0.27, 95% CI:−0.34,−0.20 for 8-iso-PGF2a and β = 0.19, 95% CI:0.11,0.28 for 8-OHdG) and uric acid with 8-OHdG (β = 0.19, 95% CI:0.11,0.26). Metabolites were involved in pathways such as the starch and sucrose metabolism and pentose and glucuronate interconversions.
Discussion
This is the first metabolomics study providing evidence of differential expression of metabolites by an organic food intervention, corroborating the reduction in biomarkers of OD. Further mechanistic evidence is warranted to better understand the biological plausibility of an organic food treatment on children’s health outcomes.
... Enzyme-linked immunosorbent assay (ELISA) technique is widely used for detection of various additives in food industries for monitoring adventitious contamination of food products by allergenic ingredients. ELISA is one of the rapid technique with high sensitivity and specificity, low detection limit, mobility, simple, and convenience to field test (Li et al., 2011;Monaci & Visconti, 2010;Sreenath & Venkatesh, 2008). The immunogen and the coating antigen are designed by introducing a carboxyl group into Amaranth for the conjugation with carrier proteins. ...
Amaranth (E 123) is synthetic dyes which commonly used in the industry and scientifically applied as textiles and paper productions as well as for cosmetic and pharmaceutical production. However, higher consumption of Amaranth may lead to hyperactivity and other disturbed behaviour especially in children. World Health Organization (WHO) with Food and Agriculture Organization (FAO) has the acceptable daily intake (ADI) of Amaranth between 0 to 0.5 mg kg⁻¹. Several extraction and analytical methods have available for quantifying and identifying the existence level of Amaranth in food products. Herein, we critically discussed those existing analytical methods applied such as high performance liquid chromatography (HPLC), thin layer chromatography (TLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), spectrophotometric, electrochemical sensor and capillary zone electrophoresis (CZE). Additionally, a brief description on the uses of different extraction methods such as solid phase extraction (SPE), liquid-liquid extraction (LLE) and membrane filtration have presented. In this review incorporated valuable information’s that intended as a guideline or idea in choosing an appropriate method for detection of Amaranth in foodstuffs.
... Erythritol (1,2,3,4-butanetetrol) is a four-carbon sugar alcohol, or polyol, and a meso-butanetetrol ( Fig. 1). It occurs naturally in some mushrooms, some fruits (e.g., watermelon, grapes and pears) and in fermented foods including wine, cheese, sake and soy sauce [1,2]. Consumption of erythritol nat-Figure 1 Two possible stereoisomers of 1,2,3,4-butanetetrol are ...
Erythritol (1,2,3,4-butanetetrol) is a non-caloric C4 polyol made by fermentation that has a sweetness 60–70% that of sucrose. The safety of erythritol has been consistently demonstrated in animal and human studies. Erythritol has a higher digestive tolerance compared to all other polyols because about 90% of the ingested erythritol is readily absorbed and excreted unchanged in urine. Erythritol is used in a wide range of applications for sweetening and other functionalities, e.g., in beverages, chewing gum and candies. In this review, we summarise the health effects of erythritol described in the literature. We focus on studies involving the anti-cariogenic and endothelial protective effects of erythritol. We conclude that erythritol could be of great importance and could be considered to be the preferred sugar substitute for a rapidly growing population of people with diabetes or pre-diabetes to reduce their risk of developing diabetic complications.
... Erythritol is a four-carbon sugar alcohol, which is applied as flavour enhancer, formulation aid, humectants, stabilizer, thickener, and as low-calorie sweetener, of which the latter is the main utilization. It has a natural occurrence in several foods including beer, sake, wine, soy sauce, water melon, pear and grape (O'Donnell and Kearsley 2012; Sreenath and Venkatesh 2008) and is well tolerated by the human body (Munro et al. 1998 ). Erythritol can be chemically synthesized from dialdehyde starch with a nickel catalyst at high temperatures, but this process is not stereospecific and low in yield, and therefore, not industrialized (Moon et al. 2010). ...
Proteins with putative erythrose reductase activity have been identified in the filamentous fungi Trichoderma reesei, Aspergillus niger, and Fusarium graminearum by in silico analysis. The proteins found in T. reesei and A. niger had earlier been characterized as glycerol dehydrogenase and aldehyde reductase, respectively. Corresponding genes from all three fungi were cloned, heterologously expressed in Escherichia coli, and purified. Subsequently, they were used to establish optimal enzyme assay conditions. All three enzymes strictly require NADPH as cofactor, whereas with NADH no activity could be observed. The enzymatic characterization of the three enzymes using ten substrates revealed high substrate specificity and activity with D-erythrose and D-threose. The enzymes from T. reesei and A. niger herein showed comparable activities, whereas the one from F. graminearum reached only about a tenth of it for all tested substrates. In order to proof in vivo the proposed enzyme function, we overexpressed the erythrose reductase-encoding gene in T. reesei. An increased production of erythritol by the recombinant strain compared to the parental strain could be detected.
... An enantioselective immunoassay using antibodies as chiral molecules which can bind the enantiomers of a chiral analyte has been developed as an emerging technique for the enantioselective analysis of analytes or drugs in foods and biological fluids (14). An immunoassay for erythritol in foods was recently described by the authors using erythritol-specific antibodies (15), and this represented the first immunoassay for † any sugar alcohol. However, an immunoassay for xylitol has not been developed so far. ...
Sugar alcohols are widely used as food additives and drug excipients. d-Xylitol (INS 967), an important five-carbon sugar alcohol, is a natural constituent of many fruits and vegetables. The critical reagent for an immunoassay of haptens is the requirement of hapten-specific antibodies. Here, affinity-purified xylitol-specific antibodies generated earlier [Sreenath, K.; Venkatesh, Y. P. Reductively aminated D-xylose-albumin conjugate as the immunogen for generation of IgG and IgE antibodies specific to D-xylitol, a haptenic allergen. Bioconjugate Chem. 2007, 18, 1995-2003] have been utilized for developing an indirect competitive ELISA for xylitol. With xylitol-BSA conjugate as the coating antigen, a working range of 5-400 ng of xylitol could be determined in the immunoassay; the limit of detection was 1 ng of xylitol. Onion (Allium cepa) and strawberry (Fragaria nilgerrensis) were selected as the food sources containing D-xylitol. The amount of D-xylitol was found to be 12.6 and 44 mg/100 g fresh weight of onion and strawberry, respectively, and the results are in good agreement with the reported values by HPLC and GC. The recovery analyses showed that added amounts of D-xylitol were recovered fairly accurately with recoveries in the range of 89.2 to 94.9% in the case of onion, and 88.4 to 95.9% in the case of strawberry. The indirect competitive ELISA for xylitol quantification is a simple method using a 3 kDa ultrafiltrate of whole food extract, and does not require extensive sample preparation and derivatization as in the case of GC and HPLC analyses. This is the first immunoassay developed for the sugar alcohol, xylitol.
This opinion addresses the re‐evaluation of erythritol (E 968) as food additive and an application for its exemption from the laxative warning label requirement as established under Regulation (EU) No 1169/2011. Erythritol is a polyol obtained by fermentation with Moniliella pollinis BC or Moniliella megachiliensis KW3‐6, followed by purifications and drying. Erythritol is readily and dose‐dependently absorbed in humans and can be metabolised to erythronate to a small extent. Erythritol is then excreted unchanged in the urine. It does not raise concerns regarding genotoxicity. The dataset evaluated consisted of human interventional studies. The Panel considered that erythritol has the potential to cause diarrhoea in humans, which was considered adverse because its potential association with electrolyte and water imbalance. The lower bound of the range of no observed adverse effect levels (NOAELs) for diarrhoea of 0.5 g/kg body weight (bw) was identified as reference point. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) at the level of the reference point. An ADI of 0.5 g/kg bw per day was considered by the Panel to be protective for the immediate laxative effect as well as potential chronic effects, secondary to diarrhoea. The highest mean and 95th percentile chronic exposure was in children (742 mg/kg bw per day) and adolescents (1532 mg/kg bw per day). Acute exposure was maximally 3531 mg/kg bw per meal for children at the 99th percentile. Overall, the Panel considered both dietary exposure assessments an overestimation. The Panel concluded that the exposure estimates for both acute and chronic dietary exposure to erythritol (E 968) were above the ADI, indicating that individuals with high intake may be at risk of experiencing adverse effects after single and repeated exposure. Concerning the new application, the Panel concluded that the available data do not support the proposal for exemption.
Riboflavin (vitamin B2), a water-soluble vitamin, plays a key role in maintaining human health. Though, numerous methods have been reported for the determination of total riboflavin (TRF) content in foods and biological samples, very few methods are reported for quantifying riboflavin and its coenzymes [flavin mononucleotide (FMN); flavin adenine dinucleotide (FAD)] individually. Recently, we have demonstrated that antibodies specific to d-ribitol and d-ribitol-5-phosphate also recognize riboflavin and FMN, respectively, and not vice-versa. In this study, we have evaluated these two antibodies for the analysis of riboflavin and FMN by indirect competitive ELISA (icELISA) in selected foods and pharmaceuticals. Under the optimal assay conditions, 50% inhibition concentration (IC50) and limit of detection (LOD, IC10) were 3.41 ng/mL and 0.02 ng/mL for riboflavin, and 7.84 ng/mL and 0.24 ng/mL for FMN, respectively, with detectable concentration range between 0.1 and 100 ng of analytes and < 0.1% cross-reactivity with other water-soluble vitamins. The amounts of TRF in food samples, as analyzed by icELISA using ribitol antibody, were 90–95% of the reported values in the literature or label values. Quantification of individual flavins (riboflavin and FMN) from the same food samples showed variation in their values compared to TRF, and were in good agreement with values obtained from HPLC and AOAC methods. Further, spiking and recovery analysis of food samples and pharmaceuticals showed no significant matrix effects. The immunoassays were validated in terms of accuracy and precision using inter- and intra-assays. The immunoassays developed in this study are sensitive and appears feasible for screening a large number of samples in the quantification of riboflavin and FMN in various biological samples, pharmaceuticals and natural/processed foods.
Sugar alcohols such as sorbitol, mannitol, xylitol, erythritol, maltitol and lactitol are widely used as additives (alternative sweeteners) in foods and as excipients in pharmaceuticals. Intravenous infusion of mannitol is the therapeutic osmotic agent of choice in various clinical situations. Xylitol is used as a therapeutic agent for the treatment of osteoporosis and ear infections. Although these sugar alcohols have enjoyed an enviable record of safety, there have been some reports of adverse reactions since 1966. In recent years, a rare case of anaphylaxis to mannitol present in pomegranate, cultivated mushroom, and a chewable drug has been described in an atopic subject. Mannitol was identified as a haptenic allergen based on positive skin prick test, mannitol-specific IgE by ELISA, and double-blind placebo-controlled food challenge. Since mannitol is a small molecule and does not contain reactive groups, a hypothesis was proposed to explain the mechanism of sensitization and hypersensitivity. The hypothesis was validated by the use of mannitol-protein conjugates prepared by reductive amination of D-mannose with proteins. Three cases of allergic reactions to erythritol in foods and one case of oral erosive eczema to xylitol in chewing gum have been reported since 2000 from the U.S. and Japan. The mechanism of sensitization and hypersensitivity to any monosaccharitol can easily be explained on the basis of the hypothesis proposed for the allergenicity of mannitol. Nonenzymic glycation of proteins with sugars in vivo leads to the production of glycated sugars which appear to be responsible for the immunogenicity and allergenicity of sugar alcohols. The proposed hypothesis for the allergenicity of sugar alcohols has also been validated to prove the immunogenicity of sugar alcohols in experimental animals. Polyclonal antiserum was generated using sugar alcohol-protein (bovine serum albumin) conjugates in rabbits. Antibodies specific to sugar alcohol was purified from the immune serum by hapten affinity chromatography on sugar alcohol-protein (keyhole limpet hemocyanin)-solid phase matrix. The specificity of the purified antibodies towards sugar alcohols was demonstrated by hapten-inhibition in ELISA; most sugars and other sugar alcohols showed minimal cross-reactivity. Further, the inhibition studies provided evidence for the haptenic and mono-epitopic nature of monosaccharitols. IgG antibodies specific to mannitol, erythritol, and xylitol have been generated in rabbits; in addition, IgE antibodies specific to xylitol have been generated in BALB/c mice by repeated intradermal administration of xylitol-protein conjugate. Antibodies specific to erythritol and xylitol have been utilized for the analysis of the respective sugar alcohols in natural and processed foods by polyclonal antibody-based indirect competitive ELISA.
