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Food & Function

Royal Society of Chemistry (RSC)

All preprints, ranked by how well they match Food & Function's content profile, based on 13 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Inducing a synergistic anti-obesity effect by increasing the bioavailability of the flavonoid rutin with a L. plantarum species

Kang, Y.-G.; Jang, S.; Seo, J.; Kim, A.-R.

2024-10-28 microbiology 10.1101/2024.10.28.620556 medRxiv
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Flavonoids, plant-derived compounds, are broadly categorized into glycoside (sugar-bonded) and aglycone (sugar-removed) forms and are predominantly found as glycosides in nature. Rutin, a glycoside, is a widely recognized flavonoid with significant potential as an anti-obesity agent. However, its low bioavailability in the body presents challenges in obesity treatment. We aimed to enhance the bioavailability and anti-obesity effect of rutin through microbial involvement. Lactiplantibacillus plantarum HAC03, one of the candidates, demonstrated the ability to hydrolyze rutin into isoquercetin and quercetin in vitro. In a diet-induced obesity mouse model, the combination of rutin and the L. plantarum strain resulted in significant weight loss, reduced adipocyte size and lowered obesity-related biomarkers in the blood, decreased fat-synthesis related gene expression, and increased fatty acid {beta}-oxidation related gene expression compared to other test groups. This includes groups treated with rutin or quercetin alone or in combination with a different species from the same Lactobacillus genus, known for its anti-obesity effect but lacking the ability to hydrolyze rutin. This synergistic combination also alleviated insulin resistance and reduced fat in the liver. Gut microbiota analysis revealed localization of L. plantarum in the ileum and beneficial changes in disrupted microbiota in the intestine. These findings provide insights into underlying mechanisms causing the synergistic effect and suggest a novel combination that is as safe as microbial monotherapies with L. plantarum or L. rhamnosus but more effective in anti-obesity treatment.

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Encapsulated Salmon Polar Lipids Modestly Reduce Postprandial Platelet Sensitivity to PAF and Thrombin in Healthy Adults: A Pilot Study.

Lordan, R.; Tsoupras, A.; Jakeman, P.; Zabetakis, I.

2025-12-04 nutrition 10.64898/2025.12.02.25341455 medRxiv
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The postprandial effects of a novel food-grade extracted salmon polar lipids (SPL) supplement against platelet-activating factor (PAF) and thrombin-induced platelet aggregation in a human pilot study was evaluated. This study was double-blinded, crossover, and placebo controlled in design. Five healthy volunteers completed 4 h time-course trials on 5 separate days. Blood was drawn at baseline before subjects consumed a standardized breakfast with one of the following treatments: a low-dose (0.25 g) or a high-dose (0.5 g) of SPL encapsulated within a stomach resistant capsule (LDSR and HDSR respectively) or a non-resistant capsule (LDSNR and HDSNR, respectively), or placebo capsules containing food-grade glycerin (0.5 g; Placebo). Blood was analyzed at 1 h intervals for 4 h. Among the treatments tested, the high-dose non-resistant capsule (HDSNR) produced the clearest postprandial effects, inducing significant increases in EC50 (reduced platelet sensitivity) for PAF at 2-3 h and for thrombin at 3-4 h post-ingestion. Smaller or delayed effects were observed with the high-dose resistant capsule (HDSR), while low-dose formulations produced minimal changes. Postprandial plasma glucose, lipid profile (TC, HDL-C, LDL-C, TG), fibrinogen, prothrombin time, and activated partial thromboplastin time remained unaffected across all trials. This pilot study provides the first in vivo indication that SPL supplementation may modestly attenuate platelet responsiveness to both PAF and thrombin without altering standard haemostatic or metabolic biomarkers. Larger controlled studies are warranted to confirm these preliminary findings and define optimal dosing and formulation strategies.

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In-vitro digestion models to examine the effects of Plant-Based Meat substitutes on Gut Microbial Metabolites

Izquierdo-Sandoval, D.; Duan, X.; Fryganas, C.; Portoles, T.; Sancho, J. V.; Rubert, J.

2023-10-26 microbiology 10.1101/2023.10.24.562654 medRxiv
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The increasing popularity of plant-based meat alternatives (PBMAs) has triggered a contentious debate about their impact on gut health in comparison to traditional animal-based meats. This study investigates the digestibility and bioavailability of a beef patty, a commercial PBMA, and a homemade pea protein-based patty by examining their influence on gut microbial metabolism. Fecal samples from five different donors were utilized to replicate colonic fermentation in vitro, with samples collected at various time points (0, 6, 12, 24, 32, and 48 hours). A rapid biochemical profiling, comparing red meat and meat analogs in terms of traditional biomarkers of gut health (ammonia, phenols, indoles, pH, and short-chain fatty acids), was conducted. Additionally, an untargeted metabolomics workflow specially designed for time-series studies, utilizing ultra-high performance liquid chromatography hyphenated to a quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS), was implemented to assess differences in terms of protein-related gut microbial metabolites (GMMs). The findings of this approach revealed notable differences in the production of intestinal inflammation markers, metabolites related to the carnitine pathways, and GMMs with signaling functions in the intestinal tract during the fermentation of animal- and plant-based burgers.

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Dietary intake of plant bioactives among European adults

Michelini, C.; Bergamo, F.; Rosi, A.; Del Rio, D.; Mena, P.

2026-04-17 nutrition 10.64898/2026.04.14.26350848 medRxiv
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This work explores the dietary intake of plant bioactives in the European adult population. The information available in the scientific literature is quite fragmented, with only partial knowledge of dietary bioactive intake and their health effects, and without harmonised figures across populations and phytochemical families. In this context, we comprehensively evaluated the intake of (poly)phenols, terpenoids, N-containing compounds, and miscellaneous phytochemicals in the European adult population, using public data from 26 countries reporting on 38,944 individuals. Further research was conducted to investigate the contributions of classes, subclasses, and individual compounds, as well as their relationships. Main food sources of each class and subclass of phytochemicals were also identified. Finally, variability in phytochemical intake across European countries was evaluated. This work significantly advances the current knowledge of plant bioactive intake and sets the stage for future research in nutrition and health fields.

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Tomato-Soy Juice Reduces Inflammation and Modulates Urinary Metabolome in Adults with Obesity

Sholola, M. J.; Miller, J.; Bilbrey, E. A.; Novotny, J. A.; Francis, D. M.; Mace, T. A.; Cooperstone, J. L.

2025-09-12 nutrition 10.1101/2025.09.11.25334465 medRxiv
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ScopeChronic, low-grade inflammation is a hallmark of many noncommunicable diseases, including obesity. Diets enriched with tomatoes and soy have been associated with better health outcomes in inflammation-related illnesses, with lycopene and isoflavones considered key bioactive components, respectively. On the basis that whole food combinations may exert greater effects than isolated phytochemicals, we examine the anti-inflammatory and metabolic effects of tomato-soy juice compared to a low carotenoid tomato juice control in obesity. Methods and resultsIn a randomized, crossover trial, 12 healthy adults with obesity were provided either tomato-soy juice (54 mg lycopene/d, 189.9 mg isoflavones/d) or a low carotenoid tomato juice (no isoflavones) daily for 4 weeks, then crossed over to the other treatment following a washout period. Plasma carotenoids, cytokines, and the urine metabolome were measured pre- and post-interventions. Plasma lycopene significantly increased by 2.48-fold after tomato-soy intake. IL-5, IL-12p70, and GM-CSF significantly decreased (P < 0.05), and TNF- trended downward (P = 0.052) following tomato-soy. Soy isoflavones and their metabolites primarily distinguished post-tomato-soy urine profiles. Both interventions induced some shared metabolomic changes in the urine, indicating tomato-driven effects independent of lycopene. ConclusionTomato-soy intake reduced some pro-inflammatory cytokines and altered the urine metabolomic profile in adults with obesity, supporting future studies using this functional food product for other inflammation-related conditions.

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Short-Chain Oat Fiber Improves Gastrointestinal Tolerance and Regulates Glucose Metabolism: A Two-Week Open-Label Study in Healthy Adults

Marcobal, A. M.; Ng, K. M.; Drexler, R. A.; McConnell, B. R.; Amicucci, M. J.

2026-01-23 nutrition 10.64898/2026.01.21.26343795 medRxiv
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IntroductionFiber intake is the most common nutritional inadequacy in the Western diet, with most adults consuming less than half of the recommended intake with only 5% of adults meeting the RDI. A novel, short-chain beta-glucan derived from oats (scOat Fiber), with improved solubility, low viscosity and enhanced palatability, compared to conventional oat fibers, was investigated for its benefits as a source of fiber supplementation. MethodsA 14-day pilot study evaluated the gastrointestinal tolerance and functional benefits of scOat Fiber in 63 healthy adults randomized to receive 5, 10 or 20 g daily doses. The primary outcome, gastrointestinal tolerability, was assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcome included glycemic response during rice challenges, measured via continuous glucose monitoring (CGM). CGM was also used to explore overall glucose dynamics. Additional exploratory outcomes (mood, energy, appetite and sleep) were assessed via validated questionnaires. ResultsscOat Fiber was exceptionally well tolerated across all doses, with no increase in GSRS scores, which remained in the low to mild range. Significant reductions in total GSRS scores were observed, with benefits evident after just one week at 5 g/day and maintained over time at both 5 and 10 g/day groups. Evaluation of GSRS sub-categories revealed that the 5 g/day and 10 g/day dose groups experienced significant reductions in abdominal pain symptoms. Both dose groups also demonstrated a significant decrease in constipation at the end of the study. Postprandial glucose responses were attenuated following product use, with a significant reduction in peak glucose during rice challenges after 2 weeks in the 20 g/day group. Both 10 and 20 g/day doses were associated with significant improvement in glycemic metrics during the study, including reductions in glucose mean, all glycemic excursions, and an increase in time-in-range. Exploratory analysis suggested that scOat Fiber may improve mental health and concentration in participants with elevated baseline symptoms. ConclusionsDespite the lack of a placebo control and short duration, the dose-dependent nature of the results supports the potential of scOat Fiber as a well-tolerated and functional source of fiber with benefits including glycemic control, digestive health and mental health (NCT06739941)

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Metabolic Responses to an Acute Glucose Challenge: The Differential Effects of Eight Weeks of Almond vs. Cracker Consumption in Young Adults

Dhillon, J.; Pandey, S.; Newman, J. W.; Fiehn, O.; Ortiz, R. M.

2024-05-20 nutrition 10.1101/2024.05.19.24307571 medRxiv
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This study investigated the dynamic responses to an acute glucose challenge following chronic almond versus cracker consumption for 8 weeks (clinicaltrials.gov ID: NCT03084003). Seventy-three young adults (age: 18-19 years, BMI: 18-41 kg/m2) participated in an 8-week randomized, controlled, parallel-arm intervention and were randomly assigned to consume either almonds (2 oz/d, n=38) or an isocaloric control snack of graham crackers (325 kcal/d, n=35) daily for 8 weeks. Twenty participants from each group underwent a 2-hour oral glucose tolerance test (oGTT) at the end of the 8-week intervention. Metabolite abundances in the oGTT serum samples were quantified using untargeted metabolomics, and targeted analyses for free PUFAs, total fatty acids, oxylipins, and endocannabinoids. Multivariate, univariate, and chemical enrichment analyses were conducted to identify significant metabolic shifts. Findings exhibit a biphasic lipid response distinguished by higher levels of unsaturated triglycerides in the earlier periods of the oGTT followed by lower levels in the latter period in the almond versus cracker group (p-value<0.05, chemical enrichment analyses). Almond (vs. cracker) consumption was also associated with higher AUC120 min of aminomalonate, and oxylipins (p-value<0.05), but lower AUC120 min of L-cystine, N-acetylmannosamine, and isoheptadecanoic acid (p-value<0.05). Additionally, the Matsuda Index in the almond group correlated with AUC120 min of CE 22:6 (r=- 0.46; p-value<0.05) and 12,13 DiHOME (r=0.45; p-value<0.05). Almond consumption for 8 weeks leads to dynamic, differential shifts in response to an acute glucose challenge, marked by alterations in lipid and amino acid mediators involved in metabolic and physiological pathways.

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Aged-black garlic (Abg10+) supplementation effect in blood lipoprotein profile in Grade I Hypertensive subjects. A randomized, triple-blind controlled trial.

Serrano, J. C.; Castro-Boque, E.; Garcia Carrasco, A.; Moran Valero, M. I.; Diez Municio, M.; Bermudez Lopez, M.; Valdivielso, J. M.; Espinel, A. E.; Portero-Otin, M.

2026-04-30 nutrition 10.64898/2026.04.20.26351262 medRxiv
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Aged black garlic (ABG) is rich in organosulfur compounds such as Sallylcysteine (SAC) and may influence lipid metabolism, although evidence from controlled trials remains limited. The aim of this study was to evaluate the impact of a low-dose SAC-optimized ABG on blood lipid profiles in Grade I hypertensive individuals. A randomized, triple-blind, placebo-controlled trial was conducted with 75 Grade I hypertensive participants receiving either 250 mg of ABG or a placebo daily for 12 weeks. Plasma lipoproteins and subclass composition were quantified by NMR spectroscopy, and metabolic clusters were explored using kmeans and PLSDA. ABG supplementation led to a significant reduction in the total number of particles and HDL particles. Detailed analysis of XXL-VLDL particles showed a significant decrease in the percentage of both free and esterified cholesterol, alongside an increase in triglyceride percentage. Conversely, large HDL particles exhibited a beneficial remodeling characterized by an increase in phospholipid content and a decrease in triglyceride percentage. Furthermore, cluster analysis demonstrated that participants with a more adverse baseline metabolic profile experienced a significant reduction in total triglycerides and VLDL-lipid content after ABG intake. These results suggest that low-dose ABG supplementation induces specific qualitative improvements in lipoprotein subclasses, particularly enhancing HDL functionality markers and reducing the cholesterol load in large VLDL particles, which may provide cardiovascular benefits in hypertensive individuals with metabolic impairment

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Oat protein nanofibril-iron hybrids as a stable, high-absorption iron delivery platform for human nutrition

Zhou, J.; Gowachirapant, S.; Zeder, C.; Wieczorek, A.; Kutzli, I.; Siol, S.; von Meyenn, F.; Zimmermann, M.; Mezzenga, R.

2025-01-27 nutrition 10.1101/2025.01.24.25321072 medRxiv
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Iron deficiency and anemia are significant global health issues, affecting nearly two billion people worldwide. The World Health Organization recommends iron fortification of foods as an effective strategy to reduce anemia rates. Available iron fortificants, however, are limited by low absorption and/or poor sensory performance. Developing new iron compounds that deliver highly bioavailable ferrous iron in foods without compromising sensory quality remains a challenge. In this work, we introduce oat protein nanofibrils (OatNF) carrying ultrasmall iron nanoparticles as promising iron fortificants for foods and beverages. Tailored synthesis of OatNF hybrids can produce iron nanoparticles in either the ferrous or ferric state. When sodium ascorbate (SA) is used as the reducing agent, the OatNF carry stabilized ferrous iron which is remarkably well absorbed in humans. In iron-deficient women, geometric mean absorption is found to be 46.2% (95% CI: 39.1%-54.7%) when given with water and 13.4% (95% CI: 9.8%-18.3%) when given with a polyphenol-rich food, representing 76% and 66% higher absorption, respectively, than the reference compound, FeSO4. When NaOH is used as the reducing agent, the OatNF carry mainly ferric iron, which is well-absorbed and shows superior sensory performance in reactive food matrices. These promising results introduce OatNF hybrids as a possible cost-effective, plant-based and organoleptic-friendly solution to the global challenge of iron deficiency anemia.

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Discovering a new biocatalytic potential of milk fat globules: in situ conversion of exogenous docosahexaenoic acid to its oxylipins

Hernandez Barrueta, T.; Nitin, N.; Taha, A. Y.

2026-05-29 biochemistry 10.64898/2026.05.26.727978 medRxiv
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Milk fat globules (MFG) are complex structures that emulsify the fat in milk and exhibit various biological activities. Using docosahexaenoic acid (DHA) as a model polyunsaturated fatty acid, we demonstrate for the first time that a MFG-enriched fraction (isolated from commercial raw and unhomogenized bovine milk) catalyzes the oxidation of exogenous polyunsaturated fatty acid to its oxylipins. Static incubation of the MFG-enriched fraction (at 20% w/v in phosphate buffer and 5% v/v ethanol) with 150 {micro}M of DHA for 1 h resulted in the production of [~]13 pmol/mg cream of DHA-derived oxylipins in free and esterified (i.e., bound) forms. High enrichment in free DHA-oxylipins was observed, wherein incubation with DHA resulted in >80% of all free oxylipins being derived from DHA, in contrast to control samples in which only <8% of all free oxylipins were DHA derivatives. The most abundant products generated were 17-hydroxydocosahexaenoic acid and 19(20)-epoxydocosapentaenoic acid. Oxylipin generation was dependent on the structural integrity of MFG, with mechanical disruption (vortexing) impairing oxylipin synthesis more severely than thermal treatment. These findings suggest that MFGs harbor multiple metabolically active enzymes, including cytochrome P450, lipoxygenases, acyl-CoA synthetases, and acyltransferases, that act cooperatively to synthesize and esterify DHA-derived oxylipins. In summary, this study highlights the dual potential of MFGs to serve both as a food-grade biocatalyst for the synthesis of DHA-derived oxylipins and as carriers for these bioactive lipids. Future studies should evaluate the bioavailability and physiological relevance of these metabolites when consumed in the diet.

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A 2-year calorie restriction intervention reduces glycomic biological age biomarkers.

Pribic, T.; Das, J. K.; Derek, L.; Belsky, D. W.; Orenduff, M.; Huffman, K. M.; Kraus, W. E.; Deris, H.; Simunovic, J.; Stambuk, T.; Hodzic, A. F.; Kraus, V. B.; Das, S. K.; Racette, S. B.; Banskota, N.; Ferruci, L.; Pieper, C.; Lewis, N. E.; Lauc, G.; Krishnan, S.

2024-12-05 nutrition 10.1101/2024.12.04.24318451 medRxiv
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Background/ObjectiveIn a subset of participants from the CALERIE Phase 2 study we evaluated the effects of 2y of [~]25% Calorie Restriction (CR) diet on IgG N-glycosylation (GlycAge), plasma and complement C3 N-glycome as markers of aging and inflammaging. MethodsPlasma samples from 26 participants in the CR group who completed the CALERIE2 trial and were deemed adherent to the intervention ([~]>10 % CR at 12 mo) were obtained from the NIA AgingResearchBiobank. Glycomic investigations using UPLC or LC-MS analyses were conducted on samples from baseline (BL), mid-intervention (12 mo) and post-intervention (24 mo), and changes resulting from the 2y CR intervention were examined. In addition, anthropometric, clinical, metabolic, DNA methylation (epigenetic) and skeletal muscle transcriptomic data were analyzed to identify aging-related changes that occurred in tandem with the N-glycome changes. ResultsFollowing the 2y CR intervention, IgG galactosylation was higher at 24mo compared to BL (p = 0.051), digalactosylation and GlycAge (the IgG-based surrogate for biological age) were not different between BL and 12mo or BL and 24mo, but increased between 12mo and 24mo (p = 0.016, 0.027 respectively). GlycAge was also positively associated with TNF- and ICAM-1 (p=0.030, p=0.017 respectively). Plasma highly branched glycans were decreased by the 2y intervention (BL vs 24 mo: p=0.013), but both plasma and IgG bisecting GlcNAcs were increased (BL vs 24mo: p<0.001, p = 0.01 respectively). Furthermore, total complement C3 protein concentrations were reduced (BL vs 24mo: p <0.001), as were Man9 glycoforms (BL vs 24mo: p<0.001), and Man10 (which is glucosylated) C3 glycoforms (BL vs 24mo: p = 0.046). Conclusions24-mos of CR was associated with several favorable, anti-aging, anti- inflammatory changes in the glycome: increased galactosylation, reduced branching glycans, and reduced GlycAge. These promising CR effects were accompanied by an increase in bisecting GlcNAc, a known pro-inflammatory biomarker. These intriguing findings linking CR, clinical, and glycomic changes may be anti-aging and inflammatory, and merit additional investigation.

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Supplementation with Berry Juice and Vitamin E Ameliorates Blood Cholesterol Level and Alters Gut Microbiota Composition

Chen, B.; Li, Y.; Li, Z.; Hu, X.; Zhen, H.; Chen, H.; Nie, C.; Hou, Y.; Jin, X.; Xiao, L.; LI, T.

2023-05-28 nutrition 10.1101/2023.05.22.23290321 medRxiv
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ScopeAntioxidants, including vitamin E (VE) and grape seed extract, as anti-aging supplementation have been widely used to improve human health. However, the role of gut microbiota in dietary antioxidant supplementation is debatable. This study aimed to assess the longitudinal impact of dietary supplementation with antioxidant compounds on body health and the gut microbiota. Methods and resultsOne hundred and twenty healthy individuals were randomly divided into a placebo group (amylodextrin) and three experimental groups ingesting different supplement (VE, grape seed extract, or mixed berry juice). Blood and fecal samples were collected during three intervention phases. We found that VE and mixed berry juice ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances of Lachnospira sp. and Faecalibacterium spp. increased in the VE and berry juice groups. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species. ConclusionJuice and VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids.

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Absorption Kinetics of Vitamins and Minerals from a Novel Nutritional Product in Healthy Adults: A Randomized, Double Blind, Placebo-Controlled Crossover Trial

Sapp, P. A.; Townsend, J. R.; Kirby, T. O.; Edwards, C. G.; LaMonica, M. B.; Ziegenfuss, T. N.; Vernge, M. J.; Akers, W. S.; Esposito, R.

2026-01-06 nutrition 10.64898/2026.01.05.25342664 medRxiv
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Background/ObjectivesNutrient interactions in multi-ingredient supplements may influence absorption and bioavailability, yet pharmacokinetic data in this context remains limited. This clinical trial assessed the post-prandial absorption kinetics of key micronutrients in AG1, a comprehensive supplement containing vitamins, minerals, probiotics, and phytonutrients. MethodsIn a randomized, double-blind, placebo-controlled crossover trial 16 healthy adults (8 males and 8 females) consumed a single serving (13g) of AG1 or a taste- and appearance-matched placebo mixed in water, following a 10-hour overnight fast. Each condition was separated by a 1-week washout. Blood samples were collected pre-consumption and at 30, 60, 90, 120, 180, 240, 360, and 480 minutes post-ingestion. Plasma concentrations of folate, calcium, zinc, vitamin C, biotin, nicotinamide, pyridoxine, riboflavin, thiamin, and hesperidin were measured. Area under the curve (AUC0-480 min) was used to assess nutrient absorption. Safety and tolerability were assessed throughout the study. Statistical analysis included repeated measures ANOVA and paired t-tests. ResultsAG1 significantly increased AUC0-480 min values (p<0.05) for all measured nutrients except pyridoxine which revealed a strong trend (p = 0.075) and hesperidin (p = 0.224). Both AG1 and placebo were well tolerated, with no serious adverse events reported. ConclusionsAcute consumption of AG1 resulted in measurable increases in circulating levels of most of the tested micronutrients, indicating effective absorption and bioavailability. These findings support the potential of AG1 to contribute meaningfully to nutritional status and overall health.

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Health benefits of a five-day at-home modified fasting program: a randomised controlled trial

Grundler, F.; Ducarmon, Q. R.; Holley, A.; Knufinke, M.; Strathmeyer, S.; Heelemann, S.; Geyer, R.; Martinez Tellez, B.; MacArthur, M. R.; Zeller, G.; Wilhelmi de Toledo, F.; Mesnage, R.

2024-11-04 nutrition 10.1101/2024.11.01.24316348 medRxiv
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BackgroundFasting has been shown to be one of the most cost-effective methods to improve cardiometabolic health. We studied a 5-day hypocaloric ([~]600 kcal/day) and ketogenic, modified fasting program (MFP) for at-home interventions. We hypothesised that this MFP induces metabolic changes comparable to 5 days of prolonged fasting (75-250kcal/day). MethodsWe tested the MFP in a two-arm randomised controlled trial where sixty-four healthy subjects were randomised to MFP or control group. Serum biochemistry analyses and questionnaires allowed for determining effects on cardiometabolic risk factors. Emotional well-being, possible side effects and physical activity were assessed with questionnaires. Biological pathways and metabolic processes were explored with nuclear magnetic resonance blood metabolomics and gut metagenomics analyses. ResultsMFP participants (n=32) experienced weight loss (-3.1 {+/-} 1.1 kg) persisting one month after the intervention. The MFP induced significant, but transient reductions, in systolic (-6.4 {+/-} 11.5 mmHg) and diastolic (-4.4 {+/-} 7.7 mmHg) blood pressure, glucose levels, HbA1c and coagulation factors. The MFP led to greater reductions in BMI (p=0.006), diastolic pressure (p = 0.009), cholesterol (p = 0.02), and LDL (p = 0.02) in individuals at risk of cardiometabolic diseases compared to healthy individuals. Total cholesterol, LDL-C and HDL-C levels continued decreasing during food reintroduction. The MFP also increased emotional and physical well-being. Blood metabolomics revealed a significant decrease in chronic inflammation markers. Shotgun metagenomics of the gut microbiome showed trends in the changes in relative abundance of the majority of bacterial species and their genomic repertoire of carbohydrate-active enzymes (CAZymes). This reflected a decrease in families metabolising dietary fibre substrates and an increase in families metabolising host-derived glycan substrates. Comparing MFP effects with a previous cohorts 5-day prolonged fasting showed similar metabolic changes. ConclusionThis MFP is safe and effectively improves cardiometabolic health and emotional well-being in healthy individuals. It offers comparable metabolic benefits to those observed during 5-day prolonged fasting in a clinic. It is safe to be practised at home, widely accessible and compatible with individuals everyday life.

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Probiotic Lactiplantibacillus plantarum VB165 improves metabolic disorders in Insulin-Resistant Mice

Xu, T.; Zhang, W.; Jiang, K.; Duan, T.; Wu, X.; Zheng, Z.; Yang, Y.; Du, Z.; Zhou, H.; Hui, Y.; Han, S.; Chen, D.; Yang, J.

2026-03-30 microbiology 10.64898/2026.03.29.715178 medRxiv
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This study investigated the effects of Lactiplantibacillus plantarum VB165, a probiotic strain with intrinsic -glucosidase inhibitor (AGI) activity, on metabolic disorders in high-fat diet (HFD)-induced insulin-resistant (IR) mice. Male C57BL/6 mice were divided into four groups: normal control diet (NCD), NCD supplemented with VB165, HFD, and HFD supplemented with VB165. After 16 weeks, VB165 supplementation significantly attenuated HFD-induced weight gain and reduced epididymal and inguinal white adipose tissue indices. VB165 also improved glucose intolerance and insulin resistance (IR), as demonstrated by oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT), and lowered fasting blood glucose, fasting insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels. Additionally, it ameliorated dyslipidemia by reducing serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), while alleviating hepatic steatosis and adipocyte hypertrophy. Mechanistically, VB165 enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1 and Occludin), reduced systemic inflammation by lowering LPS, IL-6, and IL-1{beta}. Gut microbiota analysis revealed that VB165 modulated community composition, suppressing HFD-enriched genera (e.g., Ileibacterium and Coriobacteriaceae_UCG_002) and promoting beneficial taxa (e.g., Faecalibaculum and Oscillibacter). These findings demonstrate that L. plantarum VB165 improves HFD-induced metabolic disorders via multi-target mechanisms, highlighting its potential as a probiotic intervention for IR and related metabolic diseases.

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Konjac Glucomannan Improves Body Composition and Reduced Blood Cholesterol, Inflammation, and Cardiovascular Risk in Adults with Excess Weight: A Triple-Blind, Placebo-Controlled Randomized Clinical Trial

Escobar, J. S.; Corrales-Agudelo, V.; Ortega-Sierra, O. L.; Villota-Salazar, N. A.; Rivera, D. A.; Pulgarin-Zapata, I. C.; Hernandez-Londono, M.; Lara-Guzman, O. J.; Sierra, J. A.; Alvarez-Quintero, R.; Polanco, J. P.; Munoz-Durango, K.

2026-04-20 nutrition 10.64898/2026.04.18.26351176 medRxiv
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Obesity and related cardiometabolic diseases pose significant global health challenges. Konjac glucomannan, a soluble dietary fiber, has shown promise in managing these conditions. However, rigorous studies are necessary to establish its benefits on human health. We designed a parallel-arm, triple-blind, placebo-controlled RCT to test the effects of glucomannan (3 g/day, 12 weeks) on body weight and composition, lipid profile, glucose metabolism, inflammation, adipokines, intestinal permeability, gut microbiota, and fecal metabolites in 40 adults. Participants were randomly assigned to either the glucomannan or placebo group, with both groups adhering to personalized hypocaloric diets and moderate physical activity. Outcomes were analyzed as intention-to-treat using linear mixed-effect models. Irrespective of the treatment, our intervention reduced body weight (mean: -2.39 kg; 95% CI: -3.38, -1.40), BMI (-0.83 kg/m2; -1.15, -0.52), and waist (-2.70 cm; -3.87, -1.53). Glucomannan promoted additional benefits not obtained with the placebo, reducing body fat measured by DEXA (body fat%: -2.16%; -3.04, -1.28; VAT: -20.0 cm2; - 29.2, -10.8; FMI: -0.98 kg/m2; -1.34, -0.62), LDL (-14.1 mg/dL; -23.4, -4.9), and the atherogenic index (-0.50; -0.80, -0.21). It also diminished the Framingham score of 10-year risk of coronary heart disease (-0.370; -0.625, -0.115), C reactive protein (-1.01 mg/L; -2.18, 0.15), leptin (-2.06 ng/mL; -4.48, 0.365), and leptin/adiponectin (-0.282; -0.603, 0.040). The two treatments had similar intakes, physical activity, and adherence to the intervention. There were no adverse effects. This intervention fostered health benefits in a population at high risk of cardiometabolic diseases. Konjac glucomannan was an effective co-adjuvant for further reducing risk factors.

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An empirical evaluation of simulated gastrointestinal digestion platforms for use in plant breeding, using common bean (Phaseolus vulgaris L.) as a model

Bolt, T. M.; Riggs, M.; Sun, W.; Tian, L.; Gepts, P.; Palkovic, A.; Parker, T.; Bornhorst, G. M.; Diepenbrock, C. H.

2024-05-10 plant biology 10.1101/2024.05.09.592089 medRxiv
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There remains a disconnect in plant breeding between increasing nutrient levels in crops at time of harvest and increasing bioaccessible levels of those nutrients during digestion. This study aims to develop and compare simulated digestion models for use in plant breeding and examine bioaccessible nutrient levels in common bean samples with differing seed coat coloration and patterning. The highest trait values (starch and protein hydrolysis, total phenolics, and antioxidant power) were observed from more dynamic digestion models, but even simple dynamic models showed higher trait values than a commonly used static digestion model. The use of these models provided insight on nutrient bioaccessibility; e.g., differences were observed during digestion between common bean genotypes for protein hydrolysis and between growing environments for both total phenolics and protein hydrolysis. Together, these results inform potential future pathways for applying simulated digestion models in plant breeding to improve bioaccessible nutrient levels in crops.

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Mediterranean diet related metabolite profiles and cognitive performance in a Greek population

Papandreou, C.; Papagiannopoulos, C.; Koutsonida, M.; Kanellopoulou, A.; Markozannes, G.; Polychronidis, G.; Tzakos, A. G.; Fragkiadakis, G. A.; Evangelou, E.; Ntzani, E.; Tzoulaki, I.; Aretouli, E.; Tsilidis, K.

2022-09-30 nutrition 10.1101/2022.09.29.22280504 medRxiv
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BackgroundEvidence suggests that adherence to the Mediterranean diet (MedDiet) affects human metabolism and may contribute to better cognitive performance. However, the underlying mechanisms are not clear. ObjectiveWe generated a metabolite profile for adherence to MedDiet and evaluated its cross-sectional association with aspects of cognitive performance. MethodsA total of 1,250 healthy Greek middle-aged adults from the Epirus Health Study cohort were included in the analysis. Adherence to the MedDiet was assessed using the 14-point Mediterranean Diet Adherence Screener (MEDAS); cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. A targeted metabolite profiling (n = 250 metabolites) approach was applied, using a high-throughput nuclear magnetic resonance platform. We used elastic net regularized regressions, with a 10-fold cross-validation procedure, to identify a metabolite profile for MEDAS. We evaluated the associations of the identified metabolite profile and MEDAS with cognitive tests, using multivariable linear regression models. ResultsWe identified a metabolite profile composed of 42 metabolites, mainly lipoprotein subclasses and fatty acids, significantly correlated with MedDiet adherence (Pearson r = 0.35, P-value = 5.5 x 10-37). After adjusting for known risk factors and accounting for multiple testing, the metabolite profile and MEDAS were not associated with the cognitive tests. ConclusionsA plasma metabolite profile related to better adherence to the MedDiet was not associated with the tested aspects of cognitive performance, in a middle-aged Mediterranean population.

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Development and application of a Phytochemical Food Database (PhytoFooD) to assess the intake of dietary plant bioactives

Michelini, C.; Rosi, A.; Bergamo, F.; Mignogna, C.; Scazzina, F.; Del Rio, D.; Mena, P.

2026-03-11 nutrition 10.64898/2026.03.10.26348068 medRxiv
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Plant-based foods are complex systems, where a multitude of bioactive molecules, such as (poly)phenols and carotenoids are the outcome of endless interactions defining food chemical composition. Significant progress has been made to develop reliable food composition databases that can be used to assess the intake of dietary plant bioactives. However, many lesser-known phytochemicals, like glucosinolates and monoterpenoids are often excluded, also due to the fragmented information available in the literature. Therefore, we present PhytoFooD, a comprehensive phytochemical food database that collects qualitative and quantitative information on 1,067 bioactive compounds in 1,410 plant-based foods. We evaluated the intake of main plant bioactives in European diets and demonstrated the role of concentration variability within foods in intake assessments. This database represents a promising tool for dietary intake assessors and researchers in nutrition, paving the way for a comprehensive and accurate knowledge of our diet and the interconnected health effects of plant bioactives.

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Gut microbiome couples gut and brain during calorie restriction in treating obesity

Zeng, Q.; Wang, Q.; Xiang, T.; Ou, L.; Wu, X.; Cai, K.; Geng, C.; Han, M.; Li, Z.; Li, Z.; Wang, W.; Yang, T.; Li, F.; Ma, H.; Zhao, X.; Gao, H.; Mi, N.; Zhang, C.; Tong, L.; Wang, L.; Yan, B.; Yu, Z.; Lan, C.; Wang, Z.; Wang, X.; Li, Y.; Wang, J.

2020-12-05 microbiology 10.1101/2020.12.04.406579 medRxiv
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Calorie restriction (CR) has been widely recognized for its effect in reducing body weight and alleviating diabetes in humans, as well as prolonging life span in animal studies. Gut microbiome shifts contribute to part of the effects of CR, but little is known regarding their influences except on metabolism and immunity. Here we monitored gut microbiome using metagenomics and metatranscriptomics in obese individuals undergoing CR, and revealed microbial determinants that could contribute to successful weight loss. Microbiome changes are linked to changes in blood metabolome and hormones, which eventually correlate to brain functional changes as studied using functional magnetic resonance imaging (fMRI). Brain functional shifts indicate response of central neural system (CNS) to CR, and microbiome constitutes the keystone of gut-brain axis. Animal experiment further reaffirms the gut microbiome changes, metabolic and hormonal shifts of CR, while proteomic analysis of brain tissues suggest that epigenetic modifications of key proteins could explain responses of CNS to CR. Our study establishes linkage between CR, gut microbiome, metabolome/ hormones and CNS function, and demonstrates that CR has multi-facet, coordinated effects on the host, of which many could contribute to weight loss and other beneficial effects.