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Search Results (196)

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Keywords = choline intake

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16 pages, 384 KB  
Article
Metabolic and Reproductive Responses to Peripartum Feed Supplementation in Hyperprolific Gilts
by Julia Cantin, Carlos Cantin, Olga Mitjana, Maria Teresa Tejedor, Carlos Gil-Rubio, Ana Maria Garrido and Maria Victoria Falceto
Life 2026, 16(3), 416; https://doi.org/10.3390/life16030416 - 4 Mar 2026
Viewed by 414
Abstract
Gilts have a lower capacity for voluntary feed intake and body reserves than multiparous sows, which limits their ability to cope with the needs of gestation and lactation. In this study, a nutritional supplement was formulated to support gilts during the peripartum period. [...] Read more.
Gilts have a lower capacity for voluntary feed intake and body reserves than multiparous sows, which limits their ability to cope with the needs of gestation and lactation. In this study, a nutritional supplement was formulated to support gilts during the peripartum period. Both control (C, n = 64) and treatment (T, n = 63) groups received standard commercial diets. Group T received 300gr of supplement per gilt and day for the last 35 days of gestation until the fifth day of lactation. This supplement contained calcium (Ca; 4.1%), sodium (Na; 4.0%), lysine (Lys; 1.96%), methionine (Met; 1.32%), vitamin B12 (0.3 mg/kg), choline chloride (600 mg/kg), betaine (475 mg/kg), and L-carnitine (500 mg/kg). Supplementation significantly reduced (p < 0.050) stillbirth rate, neonatal diarrhea, postpartum hypophagia, and both β-hydroxybutyrate (BHBA) and creatinine (CREA) concentrations (effect sizes: 0.240–0.993). Also, supplementation significantly increased (p < 0.050) piglet weight at birth and at 15 days of lactation and maternal backfat thickness at 26 days of lactation (effect sizes: 0.491–0.719). The concentrations of BHBA and CREA showed significant and negative associations with several productive parameters (p < 0.05); the strength of the associations was low–medium. Targeted peripartum supplementation represents a feasible nutritional strategy for commercial herds characterized by large litter sizes and limited voluntary feed intake capacity. Full article
(This article belongs to the Section Animal Science)
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16 pages, 672 KB  
Review
The Case for Establishing Choline Intake Recommendations Throughout Europe—A Narrative Review on the Importance of Choline for the European Population
by Nikolaus Rittenau and Klaus Günther
Dietetics 2026, 5(1), 12; https://doi.org/10.3390/dietetics5010012 - 25 Feb 2026
Viewed by 6361
Abstract
Choline is an essential nutrient whose physiological importance has not yet been sufficiently recognized by many European nutrition authorities. Despite convincing evidence of its crucial role in liver lipid export, one-carbon metabolism, cell membrane integrity, and nervous system development, explicit dietary recommendations for [...] Read more.
Choline is an essential nutrient whose physiological importance has not yet been sufficiently recognized by many European nutrition authorities. Despite convincing evidence of its crucial role in liver lipid export, one-carbon metabolism, cell membrane integrity, and nervous system development, explicit dietary recommendations for choline are still lacking in most European countries. In contrast, its importance has long been recognized in the national guidelines of the United States, Australia, China, and other regions. The current and rapidly spreading dietary shifts toward plant-based and vegan diets—characterized by a lower proportion of animal foods, the main sources of choline—increase the risk of suboptimal intake in broad segments of the population. Given the considerable interindividual differences in endogenous choline biosynthesis, which are influenced by sex hormones, physical activity, nutrient interactions, and genetic polymorphisms, adequate dietary intake is essential to meet physiological needs, especially during periods of increased demand such as pregnancy, lactation, and high-performance sports. This narrative review summarizes the evidence for the essentiality of choline, outlines the rationale for deriving intake recommendations for different life stages, and identifies an urgent need for coordinated action by European nutrition societies to address the growing risk of population-wide undersupply. Full article
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19 pages, 957 KB  
Article
Metabolic and Lactation Effects of Rumen-Protected Choline Supplementation in Peripartum Dairy Cows and Its Effects on Calf Growth Until Weaning
by Ugur Serbester and Melisa Topaktas
Metabolites 2026, 16(2), 122; https://doi.org/10.3390/metabo16020122 - 10 Feb 2026
Viewed by 528
Abstract
Background: This study evaluated the effects of rumen-protected choline (RUPCHOL) supplementation in dairy cows from 21 days before calving to 28 days postpartum. The objective was to determine how RUPCHOL influences metabolic status, milk composition, and subsequent calf growth until weaning. Methods: Twenty-seven [...] Read more.
Background: This study evaluated the effects of rumen-protected choline (RUPCHOL) supplementation in dairy cows from 21 days before calving to 28 days postpartum. The objective was to determine how RUPCHOL influences metabolic status, milk composition, and subsequent calf growth until weaning. Methods: Twenty-seven pregnant Holstein cows were assigned to a Control group (n = 13) or an RUPCHOL group (n = 14), both receiving a total mixed ration (TMR), with the RUPCHOL group supplemented with 15 g/day of choline chloride. Cows were monitored during prepartum, calving, and postpartum periods for body weight, body condition score, dry matter intake, rectal temperature, milk yield and composition, and blood metabolites. Results: RUPCHOL supplementation tended to reduce serum aspartate aminotransferase and lowered concentrations of non-esterified fatty acids and β-hydroxybutyrate, indicating improved metabolic status. Milk total solids, fat, and protein percentages were higher in RUPCHOL-fed cows, suggesting enhanced milk quality. Maternal supplementation did not affect colostrum immunoglobulin G (IgG) content or calf body weight and body measurements (heart girth, wither height, hip height, and body length) from birth to weaning. Conclusions: In summary, RUPCHOL supplementation improved indicators of metabolic health and milk composition of dairy cows during the peripartum period without altering calf growth outcomes. Full article
(This article belongs to the Section Animal Metabolism)
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26 pages, 4478 KB  
Article
Integration of Serum and Liver Metabolomics with Antioxidant Biomarkers Elucidates Dietary Energy Modulation of the Fatty Acid Profile in Donkey Meat
by Li Li, Yanli Zhao, Yongmei Guo, Binlin Shi, Jing Zhang, Fanzhu Meng, Fang Hui, Qingyue Zhang, Xiaoyu Guo and Sumei Yan
Antioxidants 2026, 15(1), 140; https://doi.org/10.3390/antiox15010140 - 21 Jan 2026
Viewed by 489
Abstract
Donkey meat is valued for its high protein, unsaturated fats, and low cholesterol. Fatty acid (FA) composition critically influences meat quality and is modulated by dietary energy levels. Twenty-four meat donkeys (male) were randomly divided into three groups: a low-energy group (LEG), a [...] Read more.
Donkey meat is valued for its high protein, unsaturated fats, and low cholesterol. Fatty acid (FA) composition critically influences meat quality and is modulated by dietary energy levels. Twenty-four meat donkeys (male) were randomly divided into three groups: a low-energy group (LEG), a medium-energy group (MEG), and a high-energy group (HEG). The trial lasted for 135 days, with dietary digestible energy levels adjusted during the pre-fattening, mid-fattening, and late-fattening phases according to the experimental design. The results showed that MEG and HEG interventions significantly upregulated tissue polyunsaturated fatty acid (PUFA) and n-3 PUFA content while reducing n-6/n-3 ratios, concomitant with enhanced activity and gene expression of most lipid-metabolizing enzymes. Notably, MEG further elevated antioxidant enzyme activities and anti-inflammatory mediators while suppressing pro-inflammatory factors. MEG and HEG significantly upregulated serum cholestane-3,7,12,25-tetrol-3-glucuronide and cortisol, along with hepatic choline, lysoPC(20:2(11Z,14Z)), glycocholic acid, and cholestane-3,7,12,25-tetrol-3-glucuronide. These modified metabolites were predominantly enriched in key metabolic pathways: pentose and glucuronate interconversions, primary bile acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, purine metabolism, and glutathione metabolism. Additionally, compared to HEG, MEG improved the antioxidant activities and immune signaling molecule levels with elevated pyroglutamic acid, glutathione, choline, inosine, adenine, and uric acid. Thus, moderately elevated dietary energy levels may enhance FA profiles in muscular and adipose tissues through coordinated regulation of lipid-metabolizing enzymes and associated gene expression, with serum and hepatic metabolites actively participating in these regulatory pathways. However, excessive energy intake could induce oxidative stress in donkeys. Full article
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13 pages, 1128 KB  
Article
Dietary Choline Intake During Pregnancy and Congenital Heart Defects in a Chinese Population
by Yue-Hua Li, Ziqi Xiao, Rui Guo, Baligen Rekemubieke, Wanting Hu, Xin Liu and Jiaomei Yang
Nutrients 2026, 18(1), 126; https://doi.org/10.3390/nu18010126 - 31 Dec 2025
Cited by 3 | Viewed by 839
Abstract
Background/Objectives: The impact of choline on congenital heart defects (CHDs) in humans remains unclear. This study aimed to investigate the associations between maternal dietary intakes of choline and choline derivatives during pregnancy and CHD. Methods: This case–control study included 474 cases [...] Read more.
Background/Objectives: The impact of choline on congenital heart defects (CHDs) in humans remains unclear. This study aimed to investigate the associations between maternal dietary intakes of choline and choline derivatives during pregnancy and CHD. Methods: This case–control study included 474 cases and 948 controls from hospitals in Northwest China. Pregnant women admitted for delivery were enrolled and completed a validated food frequency questionnaire to assess their dietary intake during pregnancy. A standardized questionnaire was also administered to collect additional pregnancy-related information. Mixed logistic regression models were used to estimate ORs (95%CIs) for CHD in association with choline intake. Results: Higher intakes of total choline, phosphatidylcholine, sphingomyelin, glycerophosphocholine, and phosphocholine in pregnancy were associated with reduced risks of total CHD, ventricular septal defects, and atrial septal defects, with all trend tests showing statistical significance (all p < 0.05). The ORs (95%CIs) of total CHD, comparing the highest with the lowest tertiles of intake, were 0.38 (0.24–0.61) for total choline, 0.51 (0.38–0.70) for phosphatidylcholine, 0.37 (0.26–0.51) for sphingomyelin, 0.34 (0.21–0.53) for glycerophosphocholine, and 0.53 (0.34–0.82) for phosphocholine. The inverse associations remained unchanged according to maternal age, work, education, parity, passive smoking, anemia, medication use, or folate/iron supplements use in pregnancy; however, these associations appeared to be more pronounced among pregnant women in urban areas. Conclusions: Higher maternal intake of dietary choline during pregnancy may be associated with a lower risk of CHD. Promoting choline intake in pregnant women could serve as a potential strategy for the primary prevention of fetal CHD in China. Full article
(This article belongs to the Special Issue Nutrition, Diet and Metabolism in Pregnancy)
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24 pages, 1046 KB  
Review
Eggs as a Nutrient-Rich Food with Potential Relevance to Sleep Metabolic Health, and Well-Being During the Menopausal Transition: A Narrative Review
by Lilia Convit, Christa-Marie Nicola, Charles S. Urwin, Spencer S. H. Roberts, Sze-Yen Tan, Samantha M. Hoffmann, Dominique Condo, Robin M. Daly, D. Lee Hamilton and Rhiannon M. J. Snipe
Nutrients 2025, 17(24), 3837; https://doi.org/10.3390/nu17243837 - 8 Dec 2025
Viewed by 3499
Abstract
Perimenopause and the menopausal transition are characterised by hormonal fluctuations that disrupt thermoregulation, metabolism, and sleep, contributing to adverse changes in body composition and increased cardiometabolic risk. Despite these challenges, food-based strategies to support sleep, appetite regulation, and metabolic health remain underexplored. This [...] Read more.
Perimenopause and the menopausal transition are characterised by hormonal fluctuations that disrupt thermoregulation, metabolism, and sleep, contributing to adverse changes in body composition and increased cardiometabolic risk. Despite these challenges, food-based strategies to support sleep, appetite regulation, and metabolic health remain underexplored. This narrative review synthesised current evidence on the nutritional factors influencing these outcomes, with emphasis on the potential role of eggs as a nutrient-dense, accessible dietary option for midlife women. Literature searches identified studies examining hormonal mechanisms and the effects of nutrients abundant in eggs, including high-quality protein, choline, tryptophan, melatonin, vitamin D, and antioxidants. Evidence suggests that adequate protein and choline intake may enhance sleep duration, satiety, and preserve lean mass, while vitamin D and antioxidant compounds may support muscle function and mitigate oxidative stress associated with hormonal decline. Collectively, eggs represent a practical whole-food source of nutrients that may play a role in supporting sleep, appetite regulation, and body-composition maintenance during the menopausal transition; however, further high-quality intervention studies are needed to confirm these effects. Full article
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15 pages, 1581 KB  
Perspective
Future Directions in Choline: From Neurodevelopment to Cardiometabolic Health
by Evan M. Paules, Hannah G. Petry, Jessica K. Sprinkles and Isis Trujillo-Gonzalez
Nutrients 2025, 17(22), 3618; https://doi.org/10.3390/nu17223618 - 20 Nov 2025
Cited by 2 | Viewed by 3329
Abstract
Although choline was established as an essential nutrient over three decades ago, critical questions remain about how choline regulates brain, liver, and cardiometabolic health across the lifespan. This Perspective summarizes emerging insights presented at the Future Directions in Choline Symposium: A Tribute to [...] Read more.
Although choline was established as an essential nutrient over three decades ago, critical questions remain about how choline regulates brain, liver, and cardiometabolic health across the lifespan. This Perspective summarizes emerging insights presented at the Future Directions in Choline Symposium: A Tribute to Steven H. Zeisel, which outlined three converging areas of research: (i) choline-dependent mechanisms in neurodevelopment and cognition, (ii) the link between choline metabolism and obesity, and (iii) the role of trimethylamine N-oxide (TMAO) in cardiovascular disease. Evidence from clinical and preclinical studies confirms that maternal choline intake is critical for neurogenesis, cognition, and visual system development, and that higher choline availability buffers the fetal brain against environmental and psychosocial stressors. Choline supplementation improves cognitive outcomes in fetal alcohol spectrum disorder and mitigates neurodegenerative pathology in Alzheimer’s models. In cardiometabolic health, recent data challenge the interpretation of TMAO as a causal toxin, positioning it instead as a marker of renal function. Moving forward, the field must develop validated biomarkers of choline adequacy in free-living populations, harmonize intervention protocols, and define context-specific requirements across obesity, pregnancy, and glucagon-like peptide-1 (GLP-1)-based therapy use. These efforts will refine dietary recommendations and solidify choline’s role in lifelong brain and metabolic health. Full article
(This article belongs to the Section Micronutrients and Human Health)
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19 pages, 986 KB  
Review
Selected Lipidome Components and Their Association with Perinatal Depression
by Dominika Ładno, Beata Nowak, Aleksandra Palka, Dominik Strzelecki and Oliwia Gawlik-Kotelnicka
Nutrients 2025, 17(22), 3590; https://doi.org/10.3390/nu17223590 - 17 Nov 2025
Viewed by 1489
Abstract
Background/Objectives: Perinatal depression affects approximately 21% of pregnant women and 15% postpartum, significantly impacting both maternal and child health. Lipid metabolism alterations, particularly involving fatty acids and lecithin, have been associated with mood disorders during the perinatal period. Omega-3 PUFAs (polyunsaturated fatty [...] Read more.
Background/Objectives: Perinatal depression affects approximately 21% of pregnant women and 15% postpartum, significantly impacting both maternal and child health. Lipid metabolism alterations, particularly involving fatty acids and lecithin, have been associated with mood disorders during the perinatal period. Omega-3 PUFAs (polyunsaturated fatty acids) play a key role in mood regulation and neuroinflammatory processes, while lecithin significantly influences neurotransmitter synthesis. Methods: A narrative review was conducted using PubMed, Scopus and Google Scholar for relevant articles which were qualitatively analyzed. Most of the literature included was published between 2020 and 2025 with selected earlier studies used, primarily, to outline the theoretical background. Results: This narrative review highlights substantial evidence linking components of lipidome, particularly omega-3 fatty acids and lecithin, and the occurrence of perinatal depression. Omega-3 deficiency increases antenatal depression risk by up to 6-fold. Inflammation, manifested by elevated levels of inflammatory markers (interleukin-6, tumor necrosis factor, C-reactive protein), and kynurenine pathway activation appear as central mechanisms, both of which can be modulated by PUFAs. Supplementation shows variable outcomes, with greatest efficiency for eicosapentaeonic acid (EPA)-predominant formulations (EPA/DHA ≥ 1.5). Choline is essential for fetal neurodevelopment, though evidence on lecithin and choline is inconclusive. Presumably, excessive intake and trimethylamine N-oxide (TMAO) production may contribute to depressive symptoms. Conclusions: Omega-3 PUFAs deficiency may increase the risk of perinatal depression, while supplementation appears beneficial for prevention. The findings regarding other lipid-derived compounds, specifically choline and lecithin, are inconclusive. Despite promising findings, further research is necessary to confirm the effectiveness of dietary interventions. Full article
(This article belongs to the Special Issue The Relationship Between Nutrition and Mental Health)
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25 pages, 2753 KB  
Article
Disease and Medication Context Shape Ex Vivo Metabolite Stability: A Pilot Study in Systemic Lupus Erythematosus
by Fabian Schmitt, Susanne Nguyen, Paul Christoph Claßen, Myriam Meineck, Mathias Hagen, Julia Weinmann-Menke and Thierry Schmidlin
Metabolites 2025, 15(11), 738; https://doi.org/10.3390/metabo15110738 - 12 Nov 2025
Viewed by 902
Abstract
Background/Objectives: Pre-analytical variation is a major challenge in metabolomics, yet most stability studies have focused on healthy volunteers and have overlooked the impact of disease and medication. To address this gap, we conducted a pilot study in systemic lupus erythematosus (SLE) to [...] Read more.
Background/Objectives: Pre-analytical variation is a major challenge in metabolomics, yet most stability studies have focused on healthy volunteers and have overlooked the impact of disease and medication. To address this gap, we conducted a pilot study in systemic lupus erythematosus (SLE) to assess serum metabolite stability under delayed centrifugation. Methods: Peripheral blood from 10 SLE patients and 5 healthy controls (HC) was stored at room temperature for 1–24 h before processing and analyzed by untargeted LC-MS-based metabolomics. This design enabled direct evaluation of the effect of pre-analytical delay within the context of clinical heterogeneity. Results: Principal component trajectories showed reproducible temporal shifts in HC but dispersed patterns in SLE, indicating disease- and treatment-related influences. Linear mixed-effects models identified metabolites with condition-specific kinetics, including glucose, choline, glycerophosphocholine, and pyroglutamic acid. Mycophenolate intake was further associated with distinct AMP dynamics. Conclusions: These findings demonstrate that both disease state and medication reshape apparent metabolite stability, highlighting the need for strictly controlled sample handling and well-characterized clinical cohorts in metabolomics studies. Full article
(This article belongs to the Topic Application of Analytical Technology in Metabolomics)
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16 pages, 1490 KB  
Article
Comparative Bioavailability of Vitamin C After Short-Term Consumption of Raw Fruits and Vegetables and Their Juices: A Randomized Crossover Study
by Mijoo Choi, Juha Baek, Jung-Mi Yun, Young-Shick Hong and Eunju Park
Nutrients 2025, 17(21), 3331; https://doi.org/10.3390/nu17213331 - 23 Oct 2025
Viewed by 6605
Abstract
Background/Objectives: Vitamin C plays a vital role in human health, functioning as a powerful antioxidant and enzymatic cofactor. Although vitamin C bioavailability from food versus supplements has been debated, few studies have examined how intake form affects absorption and physiological markers. Methods: This [...] Read more.
Background/Objectives: Vitamin C plays a vital role in human health, functioning as a powerful antioxidant and enzymatic cofactor. Although vitamin C bioavailability from food versus supplements has been debated, few studies have examined how intake form affects absorption and physiological markers. Methods: This randomized, controlled, crossover trial aimed to compare the bioavailability of vitamin C consumed as a supplement, through raw fruits and vegetables, or through fruit and vegetable juice. Twelve healthy adults underwent three 1-day crossover trials, each separated by a 2-week washout. Participants consumed 101.7 mg of vitamin C via powder, raw fruits and vegetables (186.8 g), or juice (200 mL). Plasma and urinary vitamin C concentrations, urinary metabolites (1H NMR), and antioxidant activity (ORAC and TRAP) were assessed over 24 h. Results: All interventions elevated plasma vitamin C levels, with juice yielding the highest AUC (25.3 ± 3.2 mg/dL·h). Urinary vitamin C increased in all groups. Metabolomics revealed increased urinary excretion of mannitol, glycine, taurine, dimethylglycine (DMG), and asparagine, and decreased choline and dimethylamine (DMA). Notably, urinary mannitol increased only in the morning. Choline significantly decreased after powder intake (p = 0.001), with similar trends observed in the other groups. DMG and glycine increased following raw and juiced vegetable intake. Antioxidant activity showed transient ORAC elevation post-powder but no sustained improvements. Conclusions: Vitamin C is bioavailable from all intake forms, with juice providing the most efficient absorption. Urinary metabolite changes suggest microbiota-related modulation, while antioxidant activity improvements were limited. Full article
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12 pages, 499 KB  
Article
Impact of Feeding Level and Multi-Nutrient Blocks with Polyherbals on Weight Changes and Greenhouse Gas Emissions in Lambs
by Nallely Sánchez-López, Germán David Mendoza-Martínez, María Eugenia de la Torre-Hernández, Pedro Abel Hernández-García, Cesar Díaz-Galván, Gilberto Carlos Ortega-Navarro, Mariela Hada Fuentes Ponce, Abel Jaime Leal-González, Santiago López Ridaura and Jelle Van Loon
Animals 2025, 15(17), 2541; https://doi.org/10.3390/ani15172541 - 29 Aug 2025
Viewed by 1072
Abstract
In small-scale livestock production systems, low-quality diets constrain animal performance and increase enteric emissions, but both these impacts can be remediated using optimized feeding strategies. An experiment was conducted with lambs fed at two levels—maintenance (MN) and growth (GR)—using multi-nutrient blocks formulated with [...] Read more.
In small-scale livestock production systems, low-quality diets constrain animal performance and increase enteric emissions, but both these impacts can be remediated using optimized feeding strategies. An experiment was conducted with lambs fed at two levels—maintenance (MN) and growth (GR)—using multi-nutrient blocks formulated with different concentrations of polyherbal nutraceuticals to compare the lambs’ reactions in terms of their productive performance and estimated enteric methane emissions. Thirty-two lambs were fed at two feeding levels—(a) maintenance (MN) at 9% CP and 1.85 Mcal ME/kg DM and (b) growth (GR) at 13.24% CP and 2.15 Mcal ME/kg DM)—and did or did not have access to MBs with different polyherbal percentages (BioCholine®, OptiLysine®, and OptiMethione® (0:0:0, 3:0:0, 3:0.75:0.25)). No interactions between the feeding level and supplementation were detected. Lambs fed at the MN level showed lower productive indicators (p < 0.001) than those fed at the GR level, with a lower dry matter intake (DMI, 512 vs. 1009 g/d), MB consumption (61 vs. 84 g/d), and daily weight gain (26 vs. 187 g/d), resulting in lower enteric methane emissions (8.74 vs. 18.18 g CH4 /d) and a lower emission intensity (15.25 vs. 16.55 CH4 g/kg DM). Supplementation with MBs improved the average daily weight gain (ADG) (p < 0.001) at the GR level, but no differences were detected at the MN level. However, lambs in the control group lost weight (−20 g/d) and those supplemented gained weight (g/d), with increases of 49 (0:0:0), 25 (3:0:0), and 52 (3:0.75:0.25). The highest ADG for lambs in the GR group was observed with MBs containing all three polyherbals (215a, 3:0.75:0.25), an intermediate ADG was seen with MBs without herbals or with Biocholine (200.75ab, 0:0:0; 198ab, 3:0:0), and the lowest ADG was observed with no MBs (134c g/d). The use of MBs reduces the time to reach market weight by 265 days, resulting in a 50% reduction in the enteric methane emissions per product (animal by animal), making multi-nutrient blocks a viable option to improve production indicators and reduce enteric methane emissions. Full article
(This article belongs to the Section Animal Nutrition)
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17 pages, 1315 KB  
Review
The Shuttling of Methyl Groups Between Folate and Choline Pathways
by Jonathan Bortz and Rima Obeid
Nutrients 2025, 17(15), 2495; https://doi.org/10.3390/nu17152495 - 30 Jul 2025
Cited by 8 | Viewed by 6317
Abstract
Methyl groups can be obtained either from the diet (labile methyl groups) or produced endogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine (SAM). The essential nutrients folate and choline (through betaine) are metabolically entwined to feed their methyl groups into C1-metabolism. A choline-deficient [...] Read more.
Methyl groups can be obtained either from the diet (labile methyl groups) or produced endogenously (methylneogenesis) via one-carbon (C1-) metabolism as S-adenosylmethionine (SAM). The essential nutrients folate and choline (through betaine) are metabolically entwined to feed their methyl groups into C1-metabolism. A choline-deficient diet in rats produces a 31–40% reduction in liver folate content, 50% lower hepatic SAM levels, and a doubling of plasma homocysteine. Similarly, folate deficiency results in decreased total hepatic choline. Thus, sufficient intakes of both folate and choline (or betaine) contribute to safeguarding the methyl balance in the body. A significant amount of choline (as phosphatidylcholine) is produced in the liver via the SAM-dependent phosphatidylethanolamine methyltransferase. Experimental studies using diets deficient in several methyl donors have shown that supplemental betaine was able to rescue not only plasma betaine but also plasma folate. Fasting plasma homocysteine concentrations are mainly determined by folate intake or status, while the effect of choline or betaine on fasting plasma homocysteine is minor. This appears to contradict the finding that approximately 50% of cellular SAM is provided via the betaine-homocysteine methyltransferase (BHMT) pathway, which uses dietary choline (after oxidation to betaine) or betaine to convert homocysteine to methionine and then to SAM. However, it has been shown that the relative contribution of choline and betaine to cellular methylation is better reflected by measuring plasma homocysteine after a methionine load test. Choline or betaine supplementation significantly lowers post-methionine load homocysteine, whereas folate supplementation has a minor effect on post-methionine load homocysteine concentrations. This review highlights the interactions between folate and choline and the essentiality of choline as a key player in C1-metabolism. We further address some areas of interest for future work. Full article
(This article belongs to the Section Nutrigenetics and Nutrigenomics)
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17 pages, 916 KB  
Review
Choline—An Essential Nutrient with Health Benefits and a Signaling Molecule
by Brianne C. Burns, Jitendra D. Belani, Hailey N. Wittorf, Eugen Brailoiu and Gabriela C. Brailoiu
Int. J. Mol. Sci. 2025, 26(15), 7159; https://doi.org/10.3390/ijms26157159 - 24 Jul 2025
Cited by 6 | Viewed by 12657
Abstract
Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and [...] Read more.
Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states. Full article
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14 pages, 569 KB  
Article
Assessing Choline, Carnitine, and Betaine Intake and Their Effects on Trimethylamine N-Oxide Levels: Validation of a Dietary Questionnaire in a Central European Population
by Witold Streb, Anna Olma, Mateusz Pajor, Alex Suchodolski, Wiktoria Staśkiewicz-Bartecka, Anita Stanjek-Cichoracka, Katarzyna Mitręga, Jacek Kowalczyk and Zbigniew Kalarus
Nutrients 2025, 17(14), 2263; https://doi.org/10.3390/nu17142263 - 9 Jul 2025
Viewed by 2213
Abstract
Background/Objectives: Trimethylamine N-oxide (TMAO) is implicated in the development of atherosclerosis and cardiovascular diseases. Preventive strategies must recognize the excessive consumption of products rich in choline, carnitine, and betaine, which are substrates essential for TMAO synthesis. The aim of this study was to [...] Read more.
Background/Objectives: Trimethylamine N-oxide (TMAO) is implicated in the development of atherosclerosis and cardiovascular diseases. Preventive strategies must recognize the excessive consumption of products rich in choline, carnitine, and betaine, which are substrates essential for TMAO synthesis. The aim of this study was to develop and validate a dietary questionnaire to assess the consumption of these compounds and investigate the correlation with serum TMAO levels in a Central European population. Methods: A dietary questionnaire was designed based on a literature review identifying foods high in TMAO precursors. The tool was validated in a prospective study with 94 participants. The theoretical relevance and reliability of the tool were assessed using factor analysis and statistical indices. Reproducibility was evaluated in a subgroup of 10 participants who completed the questionnaire a second time 24 h later. The results of the questionnaire helped us to determine factors contributing to serum TMAO levels. Results: The final questionnaire consisted of 15 questions, providing acceptable data quality (KMO = 0.654). Three main dietary factors were detected: (1) the consumption of fish products and legumes (SS loadings = 1.72; 10.78% variance), (2) the consumption of cereal products and root vegetables (SS loadings = 1.61; 10.05% variance), and (3) the consumption of meat (SS loadings = 1.47; 9.22% variance). Conclusions: The validated questionnaire is a useful tool for assessing the intake of TMAO-promoting foods in post-myocardial infarction patients from Central Europe. It may support dietary risk assessment and nutritional counseling in clinical practice, particularly for secondary cardiovascular prevention. Full article
(This article belongs to the Section Nutrition Methodology & Assessment)
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10 pages, 847 KB  
Article
Impact of a 12-Week Hypocaloric Weight Loss Diet with Mixed Tree Nuts vs. Pretzels on Trimethylamine-N-Oxide (TMAO) Levels in Overweight Adults
by Onkei Lei, Jieping Yang, Hannah H. Kang and Zhaoping Li
Nutrients 2025, 17(13), 2137; https://doi.org/10.3390/nu17132137 - 27 Jun 2025
Cited by 1 | Viewed by 1884
Abstract
Trimethylamine N-oxide (TMAO), a gut microbiome metabolite linked to cardiovascular health, can be influenced by dietary factors like choline intake and diet quality. This study compared the effects of mixed tree nuts (MTNs) and pretzels, as part of a 12-week hypocaloric weight loss [...] Read more.
Trimethylamine N-oxide (TMAO), a gut microbiome metabolite linked to cardiovascular health, can be influenced by dietary factors like choline intake and diet quality. This study compared the effects of mixed tree nuts (MTNs) and pretzels, as part of a 12-week hypocaloric weight loss diet, on TMAO levels and identified dietary predictors. Methods: Plasma samples from 95 overweight individuals consuming either 1.5 oz. of mixed tree nuts (MTNs, n = 56) or isocaloric pretzels (n = 39) daily for 12 weeks were analyzed. Nutritional data were collected at baseline and week 12 through dietary recall using the Automated Self-Administered 24 h Dietary Assessment Tool (ASA24), and the overall diet quality was assessed via the Healthy Eating Index (HEI) score. TMAO levels were determined and analyzed using linear mixed-effect models, adjusting for covariates. Wilcoxon signed-rank tests compared baseline and week 12 TMAO and weight. Multiple linear regression identified baseline predictors of TMAO. Results: Baseline demographics, anthropometric measures, HEI scores, and dietary choline intake were similar between the MTN and pretzel groups. A significant positive association was observed between baseline dietary choline and plasma TMAO levels (p = 0.012). The 12-week hypocaloric diet led to significant weight reduction in both groups (p < 0.01), but the magnitude of weight loss did not differ significantly between the MTN (−3.47 lbs) and pretzel (−4.25 lbs) groups (p = 0.18). Plasma TMAO levels decreased significantly in both groups (p < 0.01), but the between-group difference in reduction was not significant. (MTNs: −0.34 vs. pretzels: −0.37; p = 0.43). HEI scores and dietary choline intake remained unchanged, with no significant time–intervention interaction. Participants with low baseline HEI scores (≤53.72) had a more pronounced reduction in TMAO levels in the MTN group compared to the pretzel group (MTN: −0.54 vs. pretzel: −0.23; p = 0.045) over 12 weeks, despite similar weight loss. This difference was not observed in participants with higher HEI scores. Conclusions: The 12-week hypocaloric diet reduced body weight and plasma TMAO levels similarly in both MTN and pretzel groups. Participants with lower dietary quality saw a greater reduction in TMAO levels in the MTN group, suggesting MTNs may better modulate TMAO levels, especially for those with poorer baseline diets. Full article
(This article belongs to the Special Issue Impact of Optimized Nutritional Strategies on Weight Control)
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