Choline Research Articles

Tissue-nonspecific alkaline phosphatase (TNAP) is primarily known for its role in skeletal mineralization, through the hydrolysis of inorganic pyrophosphate (PPi). Here we demonstrate that TNAP-knockout mice exhibit liver steatosis and reduced serum triglyceride levels, mirroring the effects of choline deficiency, which impairs phosphatidylcholine synthesis, an essential component of VLDL. In fasting WT mice, TNAP inhibition via SBI-425 administration decreases choline levels in blood and liver. Incubating mouse or human serum with SBI-425 inhibits the dephosphorylation of phosphocholine and phosphoethanolamine, an alternative substrate for hepatic phosphatidylcholine synthesis. In hepatocytes, TNAP inhibition impedes proliferation when the medium is supplemented with phosphocholine instead of choline. Recombinant TNAP hydrolyzes phosphocholine and phosphoethanolamine with similar efficiency than PPi. X-ray diffraction and cryo-EM identified the residues in TNAP’s active site interacting with phosphocholine, PPi and the TNAP inhibitor. In summary, TNAP is the phosphatase enabling cellular choline uptake during fasting, participating in hepatic lipid metabolism.

Establishment of a LC-MS/MS method for the simultaneous quantitative determination of trimethylamine N-oxide and four precursors in human saliva.

Various methionine metabolites used in the treatment of experimental liver diseases in animals demonstrate hepatoprotective properties. The prophylactic use of choline was shown to provide intensive liver regeneration. In this study, we aim to evaluate the hepatoprotective effects of choline bitartrate in piglets, with an assessment of cytokine expression associated with the hepatobiliary system. The research was conducted using experimental pigs reared at the age of 45 days, which corresponds to the period of their early development. The use of choline bitartrate significantly reduces the expression of β transforming growth factor (TGF-β1) and pro-inflammatory interleukin 6 (IL-6) genes, at the same time as providing a significant reduction in total cholesterol and a proportional increase in HDL concentration, which is a classical anti-atherogenic factor.

An efficient and eco-friendly method was developed for synthesizing coumarin-thiazolidinone hybrids using choline hydroxide as a green catalyst. A series of arylidene derivatives (3a-i, 5) were prepared and characterized. Antimicrobial screening against Gram-positive and Gram-negative bacteria, yeast, and fungi demonstrated significant activity, particularly for compound 3c, which produced inhibition zones of up to 30.8 mm against Staphylococcus aureus, and compound 3i, which showed a MIC of 6.25 µg/mL against Escherichia coli, comparable to standard antibiotics. Structure-activity relationship analysis revealed that electron-donating substituents (-OCH₃, indolyl) markedly enhanced potency, while halogen and nitro substituents reduced activity. DFT calculations supported these findings, with 3i showing a low HOMO-LUMO gap (3.183 eV) indicating high reactivity. Molecular docking against Staphylococcus aureus dihydrofolate reductase (PDB: 2XCT) confirmed strong binding, with compound 3c achieving a docking score of -8.6 kcal/mol. These results establish coumarin-thiazolidinone hybrids as promising scaffolds for antimicrobial drug development.

Classic homocystinuria is a sulfur metabolism disorder caused by cystathionine beta synthase (CBS) deficiency. The primary aim of treatment is to maintain plasma homocysteine (Hcy) concentration within the target range. This study investigated choline status and the effect of choline supplementation in CBS-deficient homocystinuria patients with elevated Hcy levels despite standard therapy. Fifteen CBS-deficient homocystinuria patients and 20 controls with normal Hcy levels were enrolled. The study group received 1000 mg/day of choline bitartrate for 8 weeks. The control group was not given any supplements. Anthropometric measurements, biochemical tests, liver magnetic resonance proton density fat fraction imaging, and food consumption records of the participants in the study group were evaluated at baseline and at the end of the study. All participants demonstrated inadequate dietary choline intake. Choline supplementation significantly increased plasma free and total choline levels (p < 0.01) and reduced average plasma Hcy levels from 123.1 ± 52.2 to 61.1 ± 42.9 µmol/L (p < 0.01). In three of the four patients with hepatic steatosis at the beginning of the study, the condition regressed with choline supplementation. In conclusion, choline supplementation should be considered in CBS-deficient homocystinuria patients with low plasma choline and high Hcy levels despite standard therapy. Choline supplementation further decreases plasma homocysteine levels in patients with classic homocystinuria who still have elevated plasma homocysteine levels on standard therapy. Choline supplementation led to a remarkable surge in plasma free and total choline levels, which marked a significant breakthrough for classic homocystinuria patients. Remarkably, choline supplementation reversed hepatic steatosis in three out of four patients, highlighting its powerful therapeutic potential.

Lactoferrin, a multifunctional protein found in breast milk, is important for the regulation of immune function. Non-alcoholic steatohepatitis (NASH), which is characterized by hepatitis and fibrosis, has no established drug treatment. In this study, we aimed to investigate the effects of lactoferrin on hepatocyte inflammation in a mouse model of NASH induced with a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). As a method, C57BL/6JJmsSlc mice were fed CDAHFD for 14 days and simultaneously intake lactoferrin (3.3 g/kg or 6.6 g/kg) of water. Then, plasma levels aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were measured and gene expression levels of inflammatory cytokines in the liver were examined. Plasma levels of ALT and AST significantly increased in the NASH model, indicating hepatocyte inflammation, and lactoferrin intake suppressed their elevation in a dose-dependent manner. Histological analysis revealed that lactoferrin alleviated the fatty liver-associated tissue damage. Additionally, lactoferrin suppressed the gene expression of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1β, and IL-6 and the macrophage migration factor (MCP)-1, suggesting inhibition of macrophage activation. Lactoferrin also significantly reduced the expression of apoptosis-related genes (caspase 3 and p53), indicating its anti-apoptotic effects. Furthermore, lactoferrin alleviated oxidative stress by suppressing inducible nitric oxide synthase expression. These findings suggest that lactoferrin prevented liver injury in the mouse model of NASH induced by CDAHFD feeding by inhibiting macrophage-mediated inflammation and alleviating oxidative stress caused by fat accumulation.

To overcome the instability and scalability challenges of perovskite solar cells, we engineer zwitterionic choline bitartrate as a dual-functional additive. Its tartrate anions passivate undercoordinated Pb2+ defects through multidentate coordination, while choline cations suppress halide vacancy migration. This synergistic mechanism enables CsFAMA-based devices to achieve 24.92% efficiency (0.05 cm2) with exceptional scalability of 24.12% (1 cm2) and 21.37% (36 cm2 modules), while suppressing PbI2 impurities, enlarging grains, and retaining >95% of the initial power conversion efficiency after 600 h at 85 °C, establishing a new paradigm for stable, high-performance perovskite photovoltaics.

Novel ternary deep eutectic solvent coupled with in-situ-ultrasound synergistic extraction of flavonoids from Epimedium wushanense: machine learning, mechanistic investigation, and antioxidant activity

Objective: The primary objective of this study was to compare the therapeutic efficacy of five commonly used topical agents Choline Salicylate Gel, Benzocaine Gel, Lidocaine Gel, Amlexanox Oral Paste, and Povidone-Iodine Solution in treating mouth ulcers. The study aimed to evaluate their effectiveness in pain relief, reduction of inflammation, ulcer healing time, and patient satisfaction, while also assessing their safety profiles. Materials &amp; Methods: A total of 150 patients diagnosed with mouth ulcers were enrolled and randomized into five equal groups, with each group receiving one of the specified treatments. Each treatment was applied as per standard dosage guidelines for seven days. Pain intensity was measured using a visual analog scale (VAS) at baseline, Day 3, and Day 7. Ulcer size was assessed using calipers, and healing time was noted. Patient satisfaction scores and any adverse effects were also recorded. Data were analyzed using ANOVA and paired t-tests to determine statistical significance between treatment outcomes. Results: All treatments were effective in reducing pain and inflammation, though to varying extents. Choline Salicylate Gel provided rapid pain relief, while Amlexanox Oral Paste significantly accelerated healing and reduced ulcer size by Day 7. Lidocaine Gel was effective for short-term pain management but showed moderate results for inflammation and healing. Benzocaine Gel demonstrated efficient numbing effects but slower overall recovery. Povidone-Iodine Solution was effective in preventing secondary infections, although its healing efficacy lagged behind others. No severe adverse effects were reported across all treatment groups. Conclusion: Choline Salicylate Gel and Amlexanox Oral Paste proved to be the most effective treatments for mouth ulcers, combining rapid pain relief and enhanced healing outcomes. These findings suggest their potential as first-line therapies for managing oral ulcers. However, individual patient needs and tolerances should guide the choice of treatment

Dietary choline deficiency potentiates Helicobacter pylori-driven gut-liver dysfunction via microbial metabolic rewiring.

Quantitative native speciation of ppb-level metals in semiconductor-manufacturing-used strong acids and a base.

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.

BackgroundCholine is an essential micronutrient crucial for fetal neurodevelopment. Numerous rodent studies reveal that compared to maternal consumption of standard chow, maternal prenatal choline deficiency produces lifelong offspring cognitive deficits, and maternal choline supplementation produces lifelong improvements in offspring cognition. Few studies have evaluated this question in humans, with mixed results. Nonetheless, the available data raise concerns about the low choline intakes of pregnant women and highlight the need for knowledge of the functional consequences of various choline intakes during pregnancy.ObjectiveThis study will evaluate the cognitive and affective functioning of adolescents born to women who participated in a randomized controlled trial (RCT) of 2 levels of choline intake during pregnancy, with the primary aim of assessing offspring attention and spatial memory.MethodsIn a double-blind, randomized controlled choline feeding trial 26 women beginning their third trimester of pregnancy were randomly assigned to 2 groups: daily choline consumption at 480 or 930 mg/day. In this 14-year follow-up, the offspring (n=21) of these women will complete cognitive tests proctored over videoconferencing software. Cognitive function domains will be assessed using web-based software from the Cambridge Neuropsychological Test Automated Battery (CANTAB Connect). We will also assess facets of mental health using the Achenbach System of Empirically Based Assessment (ASEBA). These assessments will test the hypothesis that third-trimester maternal choline intake exerts lasting effects on offspring attention, memory, executive function, and mental health.ResultsBetween January 2009 and October 2010, 26 women beginning their third trimester of pregnancy from the Ithaca area were enrolled in the original controlled feeding study. We successfully re-recruited 21 (80%) of the original 26 offspring to this 14-year remote follow-up study. Recruitment started in August 2023 and was concluded in October 2023. Analysis is ongoing, and the first results are expected to be submitted for publication in the fall of 2025. We hypothesize that adolescent offspring born to women in the 930 mg/day group will perform better in domains of attention, memory, executive function, and mental health than offspring of women in the 480 mg/day group. This study is unique because the total maternal choline intake is precisely known, and the offspring are followed into adolescence, a time when group differences are indicative of lifelong effects of prenatal intervention.ConclusionsThe findings will provide important new information concerning the lasting functional consequences of maternal choline intake during pregnancy for offspring neurobehavioral health, thereby informing dietary recommendations and supplementation policies for pregnant women.Trial RegistrationClinicalTrials.gov: NCT05859126; https://clinicaltrials.gov/study/NCT05859126International Registered Report Identifier (IRRID)DERR1-10.2196/73508

Homocysteine leads to aortic stiffening in a rabbit model of atherosclerosis.

Abstract Carbon quantum dots (CQDs) are considered as eco‐friendly nanomaterials and suitable alternatives for traditional metal quantum dots. However, their high hydrophilicity and nanoscale size of CQDs pose a significant risk to aquatic organisms considering their widespread application. In this study, Chlorella vulgaris was selected as a model organism to assess the ecotoxicity of CQDs synthesized using choline bitartrate via a pyrolysis method. The effects of the CQDs on algal growth, antioxidant activity, photosynthetic pigment, and malondialdehyde levels have been extensively studied. Algal growth was inhibited by CQDs with a median effective concentration (EC50) &gt; 271 mg/L. After 4 days of exposure, chlorophyll content, respiratory rate, and protein content of the green alga declined by 14.0–91.75%, 73.4% and 24.4%, respectively. The CQDs caused excessive accumulation of reactive oxygen species (ROS) in Chlorella vulgaris and induced oxidative stress and physical damage to the algal cells. Our findings contribute to the potential application and risks assessment of the CQDs.

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, inflammation, and hepatocyte damage. A Western-style diet characterized by excessive n-6 polyunsaturated fatty acid (n-6 PUFA) intake, which is metabolized to pro-inflammatory arachidonic acids (AAs), might contribute to the exacerbation of NASH. Investigating the interactive effects of choline deficiency and n-6 PUFA supplementation on NASH progression, we aimed to elucidate how AA metabolites, such as leukotrienes, prostaglandins, and the CYP2J3/epoxyeicosatrienoic acids (EET) pathway influence disease pathogenesis. Rats were fed one of four diets: choline-sufficient with low n-6 PUFA and high saturated fatty acid (SFA) (C1), choline-sufficient with high n-6 PUFA (C2), choline-deficient with high n-6 PUFA (D1), or choline-deficient with low n-6 PUFA and high SFA (D2). Liver damage, inflammation, and oxidative stress in D1 were more than compared to C2 and D2 groups. Aggravation of NASH in D1 was accompanied by reduced levels of 15-deoxy-Δ12,14-prostaglandin J2 and PPAR-γ, weakening anti-inflammatory effects and lipid metabolism. Decreased CYP2J3 expression along with reduced PPAR-α levels, likely contributed to reduced anti-inflammatory EET levels, while elevated soluble epoxide hydrolase increased pro-inflammatory dihydroxyeicosatrienoic acids. Additionally, higher leukotriene C4 and 15-hydroxyeicosatetraenoic acid levels via the lipoxygenase pathway exacerbated inflammation. The combined pathway alterations in the D1 group increased inflammation, leading to elevated NF-κB expression, Kupffer cell polarization to M1, and lipid peroxidation, with n-6 PUFA interacting with choline deficiency to exacerbate these effects. Correlational analysis revealed significant associations between these pathways and inflammatory/oxidative markers. Our findings suggest that high intake of n-6 PUFA could aggravate NASH.

In order to better understand how choline-based ionic liquids can improve the process of converting sugar to bioethanol, our study examined how d-fructose interacted with aqueous solutions of choline salicylate ([Ch][Sal]), choline formate ([Ch][For]), and choline acetate ([Ch][Ace]). A series of measurements including density, speed of sound, viscosity, and electrical conductivity were performed across varying temperatures and concentrations to assess the physicochemical performance of d-fructose in the studied solutions. The obtained properties including apparent molar volume (Vφ), apparent molar isentropic compressibility (κφ), viscosity B-coefficients, and molar conductivity (Λ) were analyzed to gain insights into the nature of intermolecular interactions. The calculated standard partial molar volume (Vφ0) of d-fructose indicated enhanced interactions between d-fructose and the ionic liquids. Hepler’s constant values pointed to a structure-making tendency of d-fructose, particularly in aqueous [Ch][Sal] solutions. To further probe these interactions, DFT-COSMO calculation was employed, revealing that [Ch][Sal] exhibits preferentially the most energetically favorable interactions. Additionally, values of apparent specific volume (ASV) and apparent specific isentropic compressibility (ASIC) suggested that the ILs have a negligible influence on the inherent physical characteristics of d-fructose. As the temprature increased, the hydration number of d-fructose decreased, which can be due to the weakening of hydrogen bonding with water. These results highlight [Ch][Sal] ionic liquid as a promising medium for potentially promoting sugar-to-bioethanol conversion.Graphical

Когнитивные расстройства являются одной из самых актуальных проблем в области неврологии. Эта категория заболеваний включает в себя широкий спектр нарушений, касающихся памяти, внимания, восприятия и других познавательных функций. Особое внимание следует уделять выявлению этих расстройств на ранних, додементных стадиях. Раннее обнаружение когнитивных нарушений имеет критическое значение, поскольку на этой стадии возможна реализация медицинских мероприятий, способствующих замедлению или даже приостановке прогрессирования когнитивного снижения. Важно отметить, что многие пациенты не осознают свои когнитивные проблемы, а их близкие часто воспринимают изменения в поведении как естественные возрастные изменения. В обзоре приводятся данные о влиянии на развитие когнитивного дефицита таких факторов, как возраст, сердечно-сосудистые заболевания, эмоциональные нарушения и т.д. Наличие двух или более таких факторов риска, как правило, увеличивает вероятность развития болезни Альцгеймера. Рассматриваются возможности медикаментозной профилактики нарастания когнитивного дефицита при начальных формах когнитивного снижения наряду с немедикаментозными методами коррекции, которые в настоящее время являются основными при ведении подобных пациентов. Обсуждается возможность применения обладающего многофакторным механизмом действия экстракта гинкго билоба, который отвечает регламентированному содержанию активных ингредиентов (флавоновых гликозидов, терпенлактонов и гинкголиевой кислоты), и препаратов, направленных на восстановление или модуляцию холинергической активности. Приводятся данные исследования комбинированной формулы продукта Холин Стронг®, которая представляет собой фиксированную комбинацию холина битартрата и экстракта гинкго билоба. Исследование показало потенциальное фармакокинетическое преимущество данного продукта и обосновывает необходимость дальнейших исследований для уточнения механизмов его действия. Cognitive disorders are one of the most pressing problems in the field of neurology. This category of diseases includes a wide range of disorders related to memory, attention, perception and other cognitive functions. Special attention should be paid to the detection of these disorders in the early, pre-stage stages. Early detection of cognitive impairment is of critical importance, since at this stage it is possible to implement medical measures that help slow down or even stop the progression of cognitive decline. It is important to note that many patients are unaware of their cognitive problems, and their loved ones often perceive behavioral changes as natural age-related changes. The review provides data on the influence of such factors as age, cardiovascular diseases, emotional disorders, etc. On the development of cognitive deficits. The presence of two or more such risk factors, as a rule, increases the likelihood of developing Alzheimer’s disease. The possibilities of drug prevention of the increase in cognitive deficits in the initial forms of cognitive decline are considered along with non-drug correction methods, which are currently the main ones in the management of such patients. The possibility of using ginkgo biloba extract with a multifactorial mechanism of action, which meets the regulated content of active ingredients (flavone glycosides, terpenactones and ginkgolic acid), and drugs aimed at restoration or modulation of cholinergic activity. The data from the study of the combined formula of the Choline Strong, which is a fixed combination of choline bitartrate and ginkgo biloba extract, are presented. The study showed the potential pharmacokinetic advantage of this product and justifies the need for further research to clarify the mechanisms of its action.

Quantification of trimethylamine-N-oxide (TMAO) and its main related trimethylammonium-containing compounds in human plasma by LC-MS/MS.

Choline has been proven to be effective in maintaining liver function. However, the effect of choline, in combination with other nutrients, on the improvement of non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aimed to investigate the potential effect of the nutraceutical complex containing choline bitartrate, zinc citrate, and dl-α-Tocopheryl acetate on NAFLD in the zebrafish model. The NAFLD model was induced in zebrafish by administering thioacetamide. Experimental groups were established, including a normal control group, the model control group, the positive control group, the nutraceutical complex intervention group, and the choline bitartrate alone intervention group. The intervention was administered to the zebrafish in a water-soluble form, while the positive control group received polyene phosphatidylcholine at a concentration of 50.0 μg/mL. Notably, the protective effect of the nutraceutical complex against NAFLD is more pronounced than that observed with choline bitartrate supplementation alone. The results of transcriptomics and quantitative real-time PCR showed that the potential mechanisms underlying the effects of the nutraceutical complex might involve the upregulation of acacia, acsl1a, fbp2 gene expression, and the downregulation of tbc1d1 gene expression. These results were further validated by western blotting and overexpression experiments. Our findings indicated that choline bitartrate, zinc citrate, and dl-α-Tocopheryl acetate can help improve NAFLD. The results of this study provide evidence for the application of the nutraceutical complex in the improvement of NAFLD.