Glyconutrients

Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. Methods This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. Results There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. Conclusions Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. Trial registration UMIN, UMIN000033536 . Registered 27 July 2018.

Serine protease inhibitors (serpins) family have a complex mechanism of inhibition that requires a large scale conformational change. Antithrombin (AT), a member of serpin superfamily serves as a key regulator of the blood coagulation cascade, deficiency of which leads to thrombosis. In recent years …

Accelerating the clearance of intracellular protein aggregates through elevation of autophagy represents a viable approach for the treatment of neurodegenerative diseases. In our earlier report, we have demonstrated the enhanced degradation of mutant huntingtin protein aggregates through autophagy p …

The HT-29 human adenocarcinoma cell line has been used extensively in the study of colonic cell differentiation and colon cancer. We report here that substitution of glucose with trehalose (alpha-D-glucopyranosyl-alpha-D-glucopyranoside) depresses growth and promotes mucin-producing, goblet-like mat …

This work aimed to determine the effect of homogenization pressures and addition of trehalose on the functional properties of mandarin juice enriched …

Purpose. This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). Methods. In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. Results. Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups ( each). Mean instillation frequency was 3.1 ± 2.6 drops/day when using HT and 1.9 ± 2.2 drops/day when using HTC-gel (). A significant improvement in the quality of sleep was observed with both treatments (). Conclusions. Our results show improvement in signs and symptoms of DED in both groups. While instillation of HTC-gel resulted in a lower instillation frequency, both formulations of trehalose showed good clinical efficacy. This trial is registered with NCT02980913.

Background: Chondroitin sulfate proteoglycans (CSPGs) are the major cause of axonal regeneration failure at the site of lesion in spinal cord injury (SCI). Inflammation is believed to stimulate the upregulation of CSPGs expression. Recent evidence showed that trehalose reduces the development of inflammation in SCI. The aim of this study was to investigate the effect of trehalose on neurocan and Neural-Glial Antigen 2 (NG2) mRNA levels in SCI in rats. Methods: In this experimental study, male rats were divided into six groups (n=15). Sham (laminectomy), SCI (laminectomy and SCI), vehicle (laminectomy and SCI, treated with phosphate buffer saline), and T10, T100 and T1000 (laminectomy and SCI, treated with 10, 100 and 1000 mM trehalose). Five rats in each group were sacrificed at 1, 3 and 7 days post-injury to measure neurocan and NG2 mRNA levels in lesion. Statistical analysis was performed using Kruskal-Wallis methods followed by the Mann-Whitney test. Results: Findings indicated that SCI upregulated neurocan and NG2 mRNA levels at all times. No significant difference was observed in neurocan and NG2 gene transcripts between SCI and vehicle groups (p>0.05). However, 10 mM trehalose downregulated the mRNA level of both neurocan (0.76 and 0.65 fold) and NG2 (0.75 and 0.70 fold) at 3 and 7 days post-SCI compared to vehicle group (p p

Trehalose (TRE), a disaccharide, is absorbed slowly and gradually increases the blood glucose (GLU) level along with reducing insulin secretion. The aim of this study was twofold. First, we examined exercise performance following ingestions of either GLU, TRE, or water (WAT). The second purpose was …

Background This pilot study was part of a larger study which compared the effect of subgingival air-polishing using trehalose powder with sonic scaling on clinical parameters during supportive periodontal therapy. Within this microbiological part of the investigation subgingival samples were taken from 10 participants to analyze the survival of different bacterial species after the two different treatments as a proof of principle. Methods In 10 participants two non-adjacent, single-root teeth requiring treatment (PD =5 mm with bleeding on probing (BOP) or > 5 mm) were selected following a split-mouth design and were treated either with a sonic scaler or air-polishing device and trehalose powder. For persistent pockets (PD =4 mm and BOP or > 4 mm), treatment was repeated after 3 months. Subgingival biofilm samples were taken at baseline (BL), subsequently and three and six months after treatment. After determination of the bacterial counts (TBL), isolated bacteria were identified by MALDI-TOF-MS. If unsuccessful, PCR and 16S rDNA sequencing were performed. Results In both treatment groups, TBL decreased immediately after treatment remaining at a lower level. This confirms the findings of the larger study regarding clinical parameters showing a comparable effect on PD, BOP and CAL. Immediately after treatment, the diversity of detected species decreased significantly more than in the sonic group (p = 0.03). After 3 months, the proportion of Gram-positive anaerobic rods was lower in the air-polishing group (powder/ sonic 7%/ 25.9%, p = 0.025). Also, there was a greater reduction of Gram-negative aerobic rods for this group at this time (air-polishing/ sonic − 0.91 / -0.23 Log10 cfu/ ml, p = 0.020). Conclusion Within the limitations of this study air-polishing and sonic treatment seem to have a comparable effect on the subgingival oral biofilm during supportive periodontal treatment. Trial registration The study was registered in an international trial register (German Clinical Trial Register number DRKS 00006296) on 10th of June 2015. HTML&TRIAL_ID = DRKS00006296.

Many neurodegenerative diseases, including Huntington's, Alzheimer's and Parkinson's diseases, are characterized by protein misfolding and aggregation. The capability of trehalose to interfere with protein misfolding and aggregation has been recently evaluated by several research groups. In the pres …

(2016). Effects of trehalose supplementation on the growth performance and intestinal innate immunity of juvenile chicks. British Poultry Science: Vol. 57, No. 3, pp. 375-380.

Dry preservation of biologics in sugar glasses is regarded as a promising alternative to conventional cryopreservation. Evidence from various studies has suggested that there is a critical range of water content beyond which the viability of preserved biologics can be greatly compromised. In this study the viability of T-cells was determined as a function of end water content after microwave-assisted drying in trehalose solutions. Hydrogen-bonding and clustering phenomena in trehalose solutions of the same moisture content were also evaluated using molecular dynamics simulation. Post-rehydration viability decreased dramatically within the range of 0.1–1 gH2O/gdw. Molecular modeling revealed that as the water content approached 0.1 gH2O/gdw the matrix formed a large interconnected trehalose skeleton with a minimal number of bound water molecules scattered in the bulk. The diffusion coefficients of trehalose oxygen atoms most distant from the glycosidic linkage fluctuated around 7.5 × 10−14 m2/s within the range of 0.02–0.1 gH2O/gdw and increased again to ~1.13 × 10−13 m2/s at 0.01 gH2O/gdw and below due to the loss of water in the free volume between trehalose molecules. These insights can guide the optimal selection of final moisture contents to advance dry preservation methods.

In this study, a trehalose lipid was added to a Rhodococcus pyridinivorans-inoculated MFC to improve the power output by enhancing electron transfer. …

Epoxy resins are ubiquitous in high-performance composite applications because of their excellent mechanical strength, thermal and chemical resistance, strong adhesion, and low shrinkage after curing. Bio-based epoxy resins derived from natural products such as carbohydrates offer tremendous potential for creating new polymeric materials. Sugars and their derivatives often offer great biodegradability and functionality such as the presence of multiple hydroxyl groups that impart highly cross-linked polymer networks. Moreover, their ring structures can afford polymers with high glass transition temperatures. To develop epoxy resins containing sustainably sourced feedstocks, we designed and synthesized trehalose- and β-cyclodextrin-based carboxylic acid hardeners for epoxy resins and examined the thermal, mechanical, and adhesive properties of the resulting materials. Trehalose and β-cyclodextrin were succinylated with excess succinic anhydride, and the resulting carboxylic acid hardeners formed homogeneous mixtures with trimethylolpropane triglycidyl ether (TTE) in different carboxyl–epoxide ratios. The cured resins were found to be thermally stable (Td5 > 300 °C) and display high Young’s moduli of up to 1.4 and 1.8 GPa with mechanical strengths of 47 and 64 MPa for the trehalose- and β-cyclodextrin-based epoxy resins, respectively. Preliminary adhesion tests showed that the cured resins exhibit excellent lap-shear strengths of 3600 and 2100 psi, respectively. The resins were also degradable into water-soluble components in both aqueous acidic and basic solutions but were relatively stable from hydrolysis in neutral aqueous conditions. These results imply that this novel class of hardeners are promising feedstocks for renewable high performance epoxy resins.

PhD Thesis Abstract Background: Cancer continues to represent the main cause of mortality in the world, the second leading cause of death worldwide next to cardiovascular disease. Therefore, it is important to find effective non-toxic, inexpensive, and suitable neoadjuvant therapy with methotrexate (MTX) to decrease its dosage without lowering its chemotherapeutic efficacy. Aim:  This study aimed to investigate the antitumor effect of trehalose (TRE) on mice bearing Ehrlich ascites carcinoma (EAC) and to test whether it can enhance the anticancer potential of MTX. Materials and Methods: In this experiment, mice were assigned into 8 groups were used for assessment of antitumor activity of TRE. The antitumor activity of TRE was assessed by measuring the survival time, counting tumor cells, monitoring autophagic activity at the cellular level by flow cytometry, monitoring autophagic and apoptotic regulated genes (Caspase 3, Bec1, and Bcl2 genes ) by real-time  PCR, as well as the biochemical parameters, oxidative stress markers in liver homogenate, complete blood picture (CBC) and histological studies of all groups. Results: Treatment of EAC mice with TRE or MTX alone or in combination resulted in a significant decrease in total, viable, and non-viable tumor cells count as well as the tumor volume in comparison with EAC mice. Treatment with TRE alone or in combination MTX induced a significant increase in the hepatic antioxidant status, a significant upregulation in the gene expression of caspase 3, with the highest expression in the combined group, as compared to the non-treated EAC group. On the other hand, the same treatments resulted in a significant downregulation of Bcl2 and Bec1 genes, with the lowest expression in the combined group. These results showed a significant decrease in autophagic activities in both TRE- and TRE+MTX -treated groups as compared to the non-treated EAC group. Histopathological examination revealed normal lobular architecture with central vein and radiating hepatic cell cords in normal control mice. Conclusion: TRE is considered as an autophagic inhibitor for cancer cells which could be used as a potential neoadjuvant for the antitumor drug, MTX, and probably other chemotherapeutic compounds. This new role of TRE coupled with its apoptotic induction property on tumor cells and lack of toxicity on normal cells increases the efficacy of an antitumor drug for treating a spectrum of cancers. (This Ph.D. thesis was approved by the Faculty of Science, Tanta University, Egypt by March 31, 2018).

Background The trehalose (Tre) pathway has strong effects on growth and development in plants through regulation of carbon metabolism. Altering either Tre or trehalose 6-phosphate (T6P) can improve growth and productivity of plants as observed under different water availability. As yet, there are no reports of the effects of modification of Tre orT6P on plant performance under limiting nutrition. Results Here we report that nitrogen (N) metabolism is positively affected by exogenous application of Tre in nitrogen-deficient growing conditions. Spraying foliage of tobacco (Nicotiana tabacum) with trehalose partially alleviated symptoms of nitrogen deficiency through upregulation of nitrate and ammonia assimilation and increasing activities of nitrate reductase (NR), glycolate oxidase (GO), glutamine synthetase (GS) and glutamine oxoglutarate aminotransferase (GOGAT) with concomitant changes in ammonium (NH4 +) and nitrate (NO3 −) concentrations, glutamine and amino acids. Chlorophyll and total nitrogen content of leaves and rates of photosynthesis were increased compared to nitrogen-deficient plants without applied Tre. Total plant biomass accumulation was also higher in Tre -fed nitrogen-deficient plants, with a smaller proportion of dry weight partitioned to roots, compared to nitrogen-deficient plants without applied Tre. Consistent with higher nitrogen assimilation and growth, Tre application reduced foliar starch. Minimal effects of Tre feeding were observed on nitrogen-sufficient plants. Conclusions The data show, for the first time, significant stimulatory effects of exogenous Tre on nitrogen metabolism and growth in plants growing under deficient nitrogen. Under such adverse conditions metabolism is regulated for survival rather than productivity. Application of Tre can alter this regulation towards maintenance of productive functions under low nitrogen. This has implications for considering approaches to modifying the Tre pathway for to improve crop nitrogen-use efficiency and production.

Objective: To demonstrate the safety and tolerability of repeated high dose IV administration of trehalose (Cabaletta) in OPMD patients, as part of a phase 2 therapy trial. Background: Trehalose is a disaccharide with protein stabilizing and autophagy enhancing properties. It showed efficacy in reducing abnormal protein aggregation in animal models of several human poly A- and poly Q- mediated hereditary neurological disorders (of which OPMD is an example). Design and Methods: Eleven patients with molecularly confirmed OPMD (age: mean 63 years, range 43-78; disease duration: mean 10.6 years, range 1-24) received weekly infusion of 30 gr Cabaletta for 9-16 weeks (at time of abstract submission). Results: No drug-related adverse effects were noted, in particular no cardiovascular changes were observed. A subtle increase (mean= 5 mg[percnt]) in plasma glucose concentrations was observed 1 hour after trehalose administration. No increase in insulin levels was found. Short term glycosuria was recorded, probably due to trehalase activity in the kidney. Levels of plasma trehalose after a single administration in humans reached the expected concentrations determined in the animal studies as necessary for intracellular activity of trehalose (max. levels of 1000-2000 mgr/mL after 1 hour) and were retained up to 5 hours. Conclusions: Based on these preliminary findings, high dose IV trehalose (Cabaletta) is safe in humans. Clinical trials in OPMD and spinocerebellar atrophy type 3 are currently going on. More disorders with similar PolyA/Poly Q genotypic changes may be suitable for such trials. Disclosure: Dr. Argov has received personal compensation for activities with BioBlast Pharma as chief medical officer. Dr. Vornovitsky has nothing to disclose. Dr. Blumen has received personal compensation for activities with Bioblast Pharma as a consultant. Dr. Caraco has received personal compensation for activities with Sanofi, NeuroDerm, and Roche as a consultant. Thursday, April 23 2015, 2:00 pm-6:30 pm

Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological ...

During an investigation of subvisible particles found in lyophilized formulations of intravenous immunoglobulin, we used resonant mass measurement tec…

Countries worldwide have confirmed a staggering number of COVID-19 cases, and it is now clear that no country is immune to the SARS-CoV-2 infection. Resource-poor countries with weaker health systems are struggling with epidemics of their own and are now in a more uncertain situation with this rapidly spreading infection. Frontline healthcare workers are succumbing to the infection in their efforts to save lives. There is an urgency to develop treatments for COVID-19, yet there is limited clinical data on the efficacy of potential drug treatments. Countries worldwide implemented a stay-at-home order to “flatten the curve” and relieve the pressure on the health system, but it is uncertain how this will unfold after the economy reopens. Trehalose, a natural glucose disaccharide, is known to impair viral function through the autophagy system. Here, we propose trehalose as a potential preventative treatment for SARS-CoV-2 infection and transmission.

A widespread epidemic of Zika virus (a mosquito-borne flavivirus) infection was reported from 2015 in South and Central America. A major concern associated with the infection is the significantly increased incidence of microcephaly in fetuses born to the mothers infected with Zika virus (Mlakar et al., 2016). Researchers studying monkeys have shown that one infection with Zika virus protects the animal against future infections. Neutralizing antibodies are detected at 21 days post infection. Re-challenge at 10 weeks after the initial inoculation resulted in no detectable viral replication, indicating successfully protective immunity against the virus (Dudley et al., 2016). They also found that non-pregnant animals could clear the virus within 10 days post infection, however the virus persisted in the blood of pregnant monkeys for 35 to 70 days (Dudley et al., 2016). One possible explanation for the persistence of the virus in pregnancy is that the immune system of the mother was compromised, and she simply was not able to clear the virus as fast as the non-pregnant one. However the pregnant animal (woman) still has a certain level of immunity. Both type I interferons and type III interferons are apparently induced by Zika virus infections, and the interferons have an ability to restrict Zika virus replication in human trophoblast cells (Bayer et al., 2016; Quicke et al., 2016). The other explanation, more provocative hypothesis is that the persistence of the virus is indic...

(2021). A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control. Critical Reviews in Food Science and Nutrition. Ahead of Print.

Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

Novel liposomes composed of L-α-dimyristoylphosphatidylcholine (DMPC) and trehalose surfactant (DMTreCn) were produced by the method of sonication in buffer solution. The thickness of fixed aqueous layer of DMTreCn was larger than that of DMPC liposomes and increased in a dose-dependent manner. The remarkable inhibitory effects of DMTreCn on the growth of human hepatocellular carcinoma (HCC) (Hep-G2 and HuH-7) cells were obtained along with apoptosis, without affecting the growth of normal cells. DMTreCn induced apoptosis of Hep-G2 and HuH-7 cells through the activation of caspase-3, 8 and 9. Release of cytochrome c from mitochondria and activation of Bcl-2 family protein (BAX) were recorded, indicating that DMTreCn induced apoptosis of Hep-G2 and HuH-7 cells through mitochondrial pathway via BAX. It is noteworthy that the remarkable inhibitory effects of DMTreCn on the growth of human HCC cells were obtained along with apoptosis for the first time.

The use of sucrose-alternative sweeteners in ice cream production could satisfy requirements of modern consumers focused on natural and nutritionally …

Human cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously reported that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inh …

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose—a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps—is a known inducer of autophagy. However, according to the literature, its anti-atherosclerotic and anti-steatotic potential seem to depend on the experimental setting. The aim of our study was to comprehensively describe the influence of a prolonged treatment with orally administered trehalose on the development of atherosclerotic lesions and hepatic steatosis in apolipoprotein E knockout (apoE−/−) mice in an experimental set up reflecting both moderate and severe proatherogenic conditions: male apoE−/− mice on a chow diet (CD) and female apoE−/− mice fed with a high-fat diet (HFD). We found that exogenous trehalose inhibited atherosclerosis and attenuated hepatic steatosis in apoE−/− mice. Such effects of trehalose were not associated with changes of plasma cholesterol, low-density lipoproteins (LDL), or high-density lipoproteins (HDL). Moreover, the anti-steatotic action of trehalose in the liver was associated with the induction of autophagy. The exact molecular mechanisms of both the anti-atherosclerotic action of trehalose and its inhibitory effect on liver steatosis require further clarification.