Search Results (15)

Background/Objectives: The aim of this study was to investigate whether Gliatamin (choline alphoscerate), an acetylcholine precursor originally used to treat dementia, improves depressive symptoms in patients with type 2 diabetes. Methods: We conducted a 6-month double-blind, randomized, and placebo-controlled trial involving 49 participants with type 2 diabetes, older than 50 years, and with mild depressive symptoms; 33 and 16 participants received choline alphoscerate (800 mg/day) and a placebo, respectively. Results: At 6 months, the Hamilton Depression Rating Scale was significantly decreased in both the choline alphoscerate (15.9 ± 6.5 to 12.6 ± 5.8, p = 0.001) and placebo (15.4 ± 4.7 to 10.2 ± 3.9, p = 0.004) groups compared with baseline, without inter-group difference (p = 0.297). Meanwhile, the choline alphoscerate group showed favorable results in insulin resistance-related parameters at 6 months, including the waist circumference (WC) and the low-density lipoprotein cholesterol (LDL)/high-density lipoprotein cholesterol (HDL) ratio (p for inter-group difference vs. placebo = 0.009 and 0.092). Even after adjusting for multiple confounding factors, choline alphoscerate use was associated with an increased odds for reduction in WC (OR 18.28 [95% CI 2.27–461.35]) and a decreased odds for a high LDL/HDL ratio at 6 months (OR 0.16 [95% CI 0.03–0.76]). Conclusions: Choline alphoscerate did not show superiority over the placebo in terms of the alleviation of depressive symptoms, despite significant pre-post changes observed within the choline alphoscerate group. Nevertheless, given its positive potential for insulin resistance, the effects of choline alphoscerate on depressive mood in relation to insulin resistance in patients with type 2 diabetes require further validation. Full article

Background and Objectives: Subthreshold depression (StD) presents with depressive symptoms similar to major depressive disorder (MDD) but of lower intensity. Despite its milder form, StD is significantly prevalent in the older population, affecting up to 12.9%. StD is associated with adverse outcomes, such as an increased risk of MDD and mild cognitive impairment (MCI). Treating StD in older adults is challenging due to the limited efficacy and side effects of traditional antidepressants. As a result, clinicians often adopt a “watchful waiting” strategy, which increases the risk of StD progressing into MDD or MCI. Choline alphoscerate (α-GPC), a cholinergic drug, is indicated in the treatment of pseudodepression in the elderly, a condition that corresponds to the actual definition of StD. This review highlights the role of α-GPC in the treatment of StD in older subjects. Methods: A comprehensive review of preclinical and clinical studies was conducted, focusing on the efficacy of α-GPC in improving cognitive and behavioral functions in mental conditions and in modulating neurotransmitter systems involved in depression, such as dopamine and serotonin. Results: Evidence points to the therapeutic benefits of using α-GPC in StD as it acts on cholinergic dysfunction and cognitive impairment. Additionally, it may improve mood regulation and motivation, key factors in StD and in depressive disorders. These findings suggest that α-GPC may reduce the risk of progression from StD to MDD or MCI. Conclusions: α-GPC represents an effective and safe therapeutic option for the treatment of StD in the older population, improving clinical outcomes and enhancing the quality of life in this high-risk group. Full article

Background: Choline is an essential nutrient required for proper cell functioning. Due to its status as a precursor to acetylcholine, an important neurotransmitter connected to cognition and neuromuscular function, maintaining or enhancing choline levels is of interest. Supplementation with alpha-glycerylphosphorycholine (A-GPC) can maintain choline levels, but its ability to offer support towards cognition remains an area of ongoing research. Methods: Using a randomized, double-blind, placebo-controlled, crossover approach, 20 resistance-trained males (31.3 ± 11.0 years, 178.6 ± 7.3 cm, 84.6 ± 11.4 kg, 15.4 ± 5.6% body fat) consumed either a placebo (PL), 630 mg A-GPC (HD), or 315 mg (LD) A-GPC (GeniusPure^®, NNB Nutrition, Nanjing, China). After resting hemodynamic assessments, participants took their assigned dose and had cognitive assessments (Stroop, N-Back, and Flanker), visual analog scales, and hemodynamics evaluated 60 min after ingestion. All participants then warmed up and completed vertical jumps and bench press throws before completing a bout of lower-body resistance exercise (6 × 10 repetitions using the Smith squat at a load of 70% 1RM). Venous blood was collected 5, 15, 30, and 60 min after completion of the squat protocol to evaluate changes in growth hormones, and follow-up visual analog scales and cognitive measurements were evaluated 30 min after completing the exercise bout. Results: When compared to PL, changes in Stroop total score were statistically greater after HD (13.0 ± 8.2 vs. 5.2 ± 9.0, p = 0.013, d = 0.61) and LD (10.8 ± 7.7 vs. 5.2 ± 9.0, p = 0.046, d = 0.48) administration, in addition to significantly faster times to complete the Stroop test in the HD group when compared to PL (−0.12 ± 0.09 s vs. −0.05 ± 0.09 s, p = 0.021, d = 0.56). No significant differences between groups were found for the Flanker and N-Back assessments, while a tendency was observed for HD to have faster reaction times when compared to PL during the Flanker test. No group differences were realized for visual analog scales, physical performance, or growth hormone. Statistically significant changes in heart rate and blood pressure were observed in all groups, with all recorded values aligning with clinically accepted normative values. Conclusions: HD and LD A-GPC supplementation significantly increased cognitive performance in a group of young, healthy males as measured by changes in the Stroop Total Score and completion time of the Stroop test. These results offer unique insight into the potential for A-GPC to acutely increase cognition in a group of young, healthy males. While previous research has indicated potential for A-GPC to acutely improve cognition in clinical populations, extending these outcomes to healthy individuals can be potentially meaningful for a wide variety of populations such as athletes, race car drivers, military operators, and other non-athletic populations who desire and have a need to improve their mental performance. This study was retrospectively registered as NCT06690619 on clinicaltrials.gov. Full article

Background: With the aging process in China showing an accelerated trend, cognitive decline and impairment have become a major issue in older people. Dietary choline supplement may be a changeable lifestyle to improve this situation. Method: We analyzed 7659 adults aged over 55 in the China Health and Nutrition Survey (CHNS), evaluated cognitive function by the global cognition score, and found the association between cognitive function and dietary intake of total choline or L-alpha-glycerylphosphorylcholine (GPC). Linear and logistic mixed models with three levels were applied to analyze the association between dietary total choline/GPC intake and global cognition score, and the risk of poor cognition. Results: The average dietary intake at baseline was 178.8 mg/d for total choline, and 16.3 mg/d for GPC. After an average follow up of 6.8 years, we found that higher intake of total choline (β = 0.083, 95%CI: 0.046,0.119, p < 0.001) and GPC (β = 0.073, 95%CI: 0.034–0.111, p < 0.001) had positively associated with global cognitive scores. Additionally, higher intake of total choline had a better effect on improving the cognitive function of women (β = 0.092, 95%CI: 0.042–0.142, p < 0.01) and individuals between 55–65 years old (β = 0.089, 95%CI: 0.046–0.132, p < 0.01). However, higher GPC intake had a better effect on the cognitive function of men (β = 0.080, 95%CI: 0.020–0.141, p < 0.05). Higher total choline intake had a protective factor against poor cognition (OR = 0.762, 95%CI: 0.676,0.860, p < 0.001); the protective effect was more pronounced for women (OR = 0.750, 95%CI: 0.639,0.879, p < 0.001) and individuals aged 55–65 (OR = 0.734, 95%CI: 0.636–0.848, p < 0.001). Conclusions: higher dietary choline and GPC intake were beneficial for cognitive function, although we found that higher dietary choline was more effective in improving global cognitive scores at older ages; dietary choline should be supplemented as early as possible in old age to prevent poor cognition. Full article

Vegetables and fruits, high in starch and sugars, are promising substrates for bioethanol production, but can also yield valuable nootropic compounds, such as α-glycerylphosphorylcholine (α-GPC). This compound is a known cognitive enhancer that works by increasing the release of acetylcholine, a neurotransmitter essential for learning and memory. In this study, select root and tuber crops, as well as fruits, were subjected to Saccharomyces cerevisiae fermentation to observe the co-production of ethanol and α-GPC. The ethanol yields from these substrates were comparable to those from wheat (var. AC Andrew), ranging from 30.44 g/L (beet) to 70.04 g/L (lotus root). Aside from ethanol, α-GPC was also produced, with purple top turnip yielding 0.91 g/L, the second highest concentration after wheat (used as a reference), which produced 1.25 g/L. Although α-GPC yields in the tested substrates were lower than those from cereal grains (e.g., wheat and barley), a noteworthy observation was the production of methanol in many of these substrates. Methanol was detected in all feedstocks except wheat, with concentrations ranging from 0.10 g/L (cassava) to 1.69 g/L (purple top turnip). A linear regression analysis revealed a strong correlation between methanol and α-GPC content (R² = 0.876; slope = 0.52), suggesting a potential link in their biosynthetic pathways. These feedstocks not only proved effective as substrates for bioethanol production, but also showed potential for generating value-added compounds such as α-GPC. This dual-purpose potential presents new market opportunities for producers by leveraging both biofuel and nootropic compound production. Furthermore, the observed relationship between methanol and α-GPC production warrants further investigation to elucidate the metabolic pathways involved. Full article

L-α-Glycerylphosphorylcholine (L-α-GPC) has mainly been produced by two methods: extraction from plants rich in phosphatidylcholine and chemical synthesis. However, production through extraction involves difficult processes, such as fermentation, extractions and ripening, and conventional chemical synthesis methods with high-cost reactants and a batch reactor. These methods are not ideal for large-quantity production. Thus, it is important to develop a simple production method of L-α-GPC, which is suitable for mass production without the need for expensive reactants. Here, we studied synthetic L-α-GPC methods that are applicable to a flow synthesis system, which can provide selectivity, reproducibility, scalability, and a high yield in short reaction time using inexpensive starting materials. We developed a two-step synthetic route to produce L-α-GPC, including the synthesis of phosphoryl choline using choline chloride and phosphoryl oxychloride (POCl₃) as a first step and synthesis of L-α-GPC by reacting phosphoryl choline with (R)-($-$)-3-chloro-1,2-propanediol (CPD) as a second step under basic conditions. Both steps were separately performed in a customized flow reactor, and reaction conditions were optimized. Finally, phosphoryl choline and L-α-GPC, the products first and second reactions, were successfully synthesized with high conversion yields of 97% and 79%, respectively. Full article

Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients. From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis. Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (<12 mos) (38.3 vs. 24.0 mos, p = 0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314–0.900). Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings. Full article

The current study examined the effects of Alpha-Glycerylphosphorylcholine (A-GPC) on heart rate variability (HRV) and hemodynamic responses following a sprint interval exercise (SIE) in women who were overweight or obese. Participants (n = 12, 31.0 ± 4.6 years; 29.4 ± 2.1 kg/m²) consumed 1000 mg of A-GPC or a placebo after eating breakfast in a randomized, double-blind cross-over design. After 60 min, participants performed two bouts of the SIE (30 s Wingate) interspersed with 4 min of active recovery (40 rpm). Hemodynamic variables and HRV domains were measured before and 60 min after the A-GPC consumption, immediately after SIE, and every 15 min up to 120 min during recovery. A-GPC consumption increased resting levels of both the time domain (Standard Deviation of RR wave intervals [SDNN] and percentage of interval differences of adjacent RR intervals greater than 50 ms [pNN50%]) and frequency domain (high frequency [HF] and low frequency [LF]) variables of HRV (p < 0.05). Moreover, HRV variables (except for LF/HF) decreased (p < 0.05) immediately after SIE in the A-GPC and placebo sessions. Systolic and diastolic blood pressure increased (p < 0.05) immediately after SIE in both trials. Both HRV and hemodynamic variables recovered (p < 0.05) faster in the A-GPC compared to the placebo session. We concluded that A-GPC consumption recovers HRV and blood pressure faster following strenuous exercise in overweight and obese women, and that it might favorably modify cardiac autonomic function. Full article

Phospholipase B (PLB) harbors three distinct activities with broad substrate specificities and application fields. Its hydrolyzing of sn-1 and sn-2 acyl ester bonds enables it to catalyze the production of L-alpha-glycerylphosphorylcholine (L-α-GPC) from phosphatidylcholine (PC) without speed-limiting acyl migration. This work was intended to obtain high-level active PLB and apply it to establish an efficient system for L-α-GPC synthesis. PLB from Pseudomonas fluorescens was co-expressed with five different molecular chaperones, including trigger factor (Tf), GroEL-GroES (GroELS), DnaK-DnaJ-GrpE (DnaKJE), GroELS and DnaKJE, or GroELS and Tf or fused with maltose binding protein (MBP) in Escherichia coli BL21(DE3) to improve PLB expression. PLB with DnaKJE-assisted expression exhibited the highest catalytic activity. Further optimization of the expression conditions identified an optimal induction OD₆₀₀ of 0.8, IPTG concentration of 0.3 mmol/L, induction time of 9 h, and temperature of 25 °C. The PLB activity reached a maximum of 524.64 ± 3.28 U/mg under optimal conditions. Subsequently, to establish an efficient PLB-catalyzed system for L-α-GPC synthesis, a series of organic-aqueous mixed systems and surfactant-supplemented aqueous systems were designed and constructed. Furthermore, the factors of temperature, reaction pH, metal ions, and substrate concentration were further systematically identified. Finally, a high yield of 90.50 ± 2.21% was obtained in a Span 60-supplemented aqueous system at 40 °C and pH 6.0 with 0.1 mmol/L of Mg²⁺. The proposed cost-effective PLB production and an environmentally friendly PLB-catalyzed system offer a candidate strategy for the industrial production of L-α-GPC. Full article

L-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC supplementation increases incident stroke risk thus its potential adverse effects warrant further investigation. Here we show that GPC promotes atherosclerosis in hyperlipidemic Apoe^−/− mice. GPC can be metabolized to trimethylamine N-oxide, a pro-atherogenic agent, suggesting a potential molecular mechanism underlying the observed atherosclerosis progression. GPC supplementation shifted the gut microbial community structure, characterized by increased abundance of Parabacteroides, Ruminococcus, and Bacteroides and decreased abundance of Akkermansia, Lactobacillus, and Roseburia, as determined by 16S rRNA gene sequencing. These data are consistent with a reduction in fecal and cecal short chain fatty acids in GPC-fed mice. Additionally, we found that GPC supplementation led to an increased relative abundance of choline trimethylamine lyase (cutC)-encoding bacteria via qPCR. Interrogation of host inflammatory signaling showed that GPC supplementation increased expression of the proinflammatory effectors CXCL13 and TIMP-1 and activated NF-κB and MAPK signaling pathways in human coronary artery endothelial cells. Finally, targeted and untargeted metabolomic analysis of murine plasma revealed additional metabolites associated with GPC supplementation and atherosclerosis. In summary, our results show GPC promotes atherosclerosis through multiple mechanisms and that caution should be applied when using GPC as a nutritional supplement. Full article

Alpha-glycerylphosphorylcholine (αGPC) is a precursor of acetylcholine and can increase acetylcholine concentration in the brain. In addition, αGPC has a role in cholinergic function as well as monoaminergic transmission, including dopaminergic and serotonergic systems. These monoaminergic systems are related to feelings and emotions, including motivation, reward processing, anxiety, and depression. However, the precise effects of αGPC on human feelings and emotions remain to be elucidated. In this study, we investigated changes in the subjective feelings of healthy volunteers using the KOKORO scale before and after administering αGPC. Thirty-nine volunteers participated in a single-blind, placebo-controlled design. Participants completed a KOKORO scale test to quantify self-reported emotional states, three times each day for two weeks preceding treatment and then for a further two weeks while self-administering treatment. αGPC treatment show a tendency to increase motivation during the intervention period. Furthermore, motivation at night was significantly higher in the αGPC group than in the placebo group (p < 0.05). However, αGPC did not show any effects on anxiety. These data suggest that αGPC can be used to increase motivation in healthy individuals. Full article

As barley and oat production have recently increased in Canada, it has become prudent to investigate these cereal crops as potential feedstocks for alcoholic fermentation. Ethanol and other coproduct yields can vary substantially among fermented feedstocks, which currently consist primarily of wheat and corn. In this study, the liquified mash of milled grains from 28 barley (hulled and hull-less) and 12 oat cultivars were fermented with Saccharomyces cerevisiae to determine concentrations of fermentation products (ethanol, isopropanol, acetic acid, lactic acid, succinic acid, α-glycerylphosphorylcholine (α-GPC), and glycerol). On average, the fermentation of barley produced significantly higher amounts of ethanol, isopropanol, acetic acid, succinic acid, α-GPC, and glycerol than that of oats. The best performing barley cultivars were able to produce up to 78.48 g/L (CDC Clear) ethanol and 1.81 g/L α-GPC (CDC Cowboy). Furthermore, the presence of milled hulls did not impact ethanol yield amongst barley cultivars. Due to its superior ethanol yield compared to oats, barley is a suitable feedstock for ethanol production. In addition, the accumulation of α-GPC could add considerable value to the fermentation of these cereal crops. Full article

Heat stress (HS) negatively affects meat quality by affecting material and energy metabolism, and exploring the mechanism underlying the muscle response to chronic HS in finishing pigs is important for the global pork industry. This study investigated changes in the metabolic profiles of the longissimus dorsi (LD) muscle of finishing pigs under high temperature using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) and multivariate data analysis (MDA). Castrated male DLY pigs (Duroc × Landrance × Yorkshire pigs, n = 24) from 8 litters were divided into three treatment groups: constant optimal ambient temperature at 22 °C and ad libitum feeding (CR, n = 8); constant high ambient temperature at 30 °C and ad libitum feeding (HS, n = 8); and constant optimal ambient temperature 22 °C and pair-feeding to the control pigs (PF, n = 8). The metabolic profile data from LD muscle samples were analyzed by MDA and external search engines. Nine differential metabolites (L-carnosine, acetylcholine, inosinic acid, L-carnitine, L-anserine, L-α-glycerylphosphorylcholine, acetylcarnitine, thiamine triphosphate, and adenosine thiamine diphosphate) were involved in antioxidant function, lipid metabolism, and cell signal transduction, which may decrease post mortem meat quality and play important roles in anti-HS. Four metabolites (L-carnosine, acetylcholine, inosinic acid, and L-carnitine) were verified, and it was indicated that the muscle L-carnitine content was significantly lower in HS than in CR (p < 0.01). The results show that constant HS affects the metabolites in the LD muscle and leads to coordinated changes in the endogenous antioxidant defense and meat quality of finishing pigs. These metabonomics results provide a basis for researching nutritional strategies to reduce the negative effects of heat stress on livestock and present new insights for further research. Full article

Microenvironment modification within nanoconfinement can maximize the catalytic activity of enzymes. Phospholipase A₁ (PLA₁) has been used as the biocatalyst to produce high value L-α-glycerylphosphorylcholine (L-α-GPC) through hydrolysis of phosphatidylcholine (PC). We successfully developed a simple co-precipitation method to encapsulate PLA₁ in a metal–surfactant nanocomposite (MSNC), then modified it using alkalescent 2-Methylimidazole (2-Melm) to promote catalytic efficiency in biphasic systems. The generated 2-Melm@PLA₁/MSNC showed higher catalytic activity than PLA₁/MSNC and free PLA₁. Scanning electron microscopy and transmission electron microscopy showed a typical spherical structure of 2-Melm@PLA₁/MSNC at about 50 nm, which was smaller than that of 2-Melm@MSNC. Energy disperse spectroscopy, N₂ adsorption isotherms, Fourier transform infrared spectrum, and high-resolution X-ray photoelectron spectroscopy proved that 2-Melm successfully modified PLA₁/MSNC. The generated 2-Melm@PLA₁/MSNC showed a high catalytic rate per unit enzyme mass of 1.58 μmol mg^-1 min^-1 for the formation of L-α-GPC. The 2-Melm@PLA₁/MSNC also showed high thermal stability, pH stability, and reusability in a water–hexane biphasic system. The integration of alkaline and amphiphilic properties of a nanocomposite encapsulating PLA₁ resulted in highly efficient sequenced reactions of acyl migration and enzymatic hydrolysis at the interface of a biphasic system, which cannot be achieved by free enzyme. Full article

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional ¹H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n = 15) and IDH2 (n = 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38, P_c < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, P_c = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine. Full article