-
Frontiers in Endocrinology 2023In this comprehensive review, we examine the main preclinical and clinical investigations assessing the effects of different forms of choline supplementation currently... (Review)
Review
In this comprehensive review, we examine the main preclinical and clinical investigations assessing the effects of different forms of choline supplementation currently available, including choline alfoscerate (CHNOP), also known as alpha-glycerophosphocholine (α-GPC, or GPC), choline bitartrate, lecithin, and citicoline, which are cholinergic compounds and precursors of acetylcholine. Extensively used as food supplements, they have been shown to represent an effective strategy for boosting memory and enhancing cognitive function.
Topics: Choline; Glycerylphosphorylcholine; Acetylcholine; Dietary Supplements; Cytidine Diphosphate Choline
PubMed: 36950691
DOI: 10.3389/fendo.2023.1148166 -
Current Opinion in Gastroenterology Mar 2012Choline is an essential nutrient and the liver is a central organ responsible for choline metabolism. Hepatosteatosis and liver cell death occur when humans are deprived... (Review)
Review
PURPOSE OF REVIEW
Choline is an essential nutrient and the liver is a central organ responsible for choline metabolism. Hepatosteatosis and liver cell death occur when humans are deprived of choline. In the last few years, there have been significant advances in our understanding of the mechanisms that influence choline requirements in humans and in our understanding of choline's effects on liver function. These advances are useful in elucidating why nonalcoholic fatty liver disease (NAFLD) occurs and progresses sometimes to hepatocarcinogenesis.
RECENT FINDINGS
Humans eating low-choline diets develop fatty liver and liver damage. This dietary requirement for choline is modulated by estrogen and by single-nucleotide polymorphisms in specific genes of choline and folate metabolism. The spectrum of choline's effects on liver range from steatosis to development of hepatocarcinomas, and several mechanisms for these effects have been identified. They include abnormal phospholipid synthesis, defects in lipoprotein secretion, oxidative damage caused by mitochondrial dysfunction, and endoplasmic reticulum stress. Furthermore, the hepatic steatosis phenotype can be characterized more fully via metabolomic signatures and is influenced by the gut microbiome. Importantly, the intricate connection between liver function, one-carbon metabolism, and energy metabolism is just beginning to be elucidated.
SUMMARY
Choline influences liver function, and the dietary requirement for this nutrient varies depending on an individual's genotype and estrogen status. Understanding these individual differences is important for gastroenterologists seeking to understand why some individuals develop NAFLD and others do not, and why some patients tolerate total parenteral nutrition and others develop liver dysfunction.
Topics: Animals; Choline; Disease Progression; Fatty Liver; Humans; Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
PubMed: 22134222
DOI: 10.1097/MOG.0b013e32834e7b4b -
Nutrients Aug 2020Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon... (Review)
Review
Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.
Topics: Animals; Biological Availability; Cardiovascular Diseases; Choline; Diet; Dysbiosis; Gastrointestinal Microbiome; Genotype; Humans; Inflammatory Bowel Diseases; Liver; Methylamines; Non-alcoholic Fatty Liver Disease; Renal Insufficiency, Chronic
PubMed: 32764281
DOI: 10.3390/nu12082340 -
Signal Transduction and Targeted Therapy Jul 2022Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO...
Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR's metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P < 0.05; *P < 0.05), and 37 and 35% in plasma (***P < 0.001; *P < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.
Topics: Animals; Atherosclerosis; Choline; Cricetinae; Gastrointestinal Microbiome; Methylamines; Vitamins
PubMed: 35794102
DOI: 10.1038/s41392-022-01027-6 -
FASEB Journal : Official Publication of... Apr 2018Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the... (Randomized Controlled Trial)
Randomized Controlled Trial
Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.
Rodent studies demonstrate that supplementing the maternal diet with choline during pregnancy produces life-long cognitive benefits for the offspring. In contrast, the two experimental studies examining cognitive effects of maternal choline supplementation in humans produced inconsistent results, perhaps because of poor participant adherence and/or uncontrolled variation in intake of choline or other nutrients. We examined the effects of maternal choline supplementation during pregnancy on infant cognition, with intake of choline and other nutrients tightly controlled. Women entering their third trimester were randomized to consume, until delivery, either 480 mg choline/d ( n = 13) or 930 mg choline/d ( n = 13). Infant information processing speed and visuospatial memory were tested at 4, 7, 10, and 13 mo of age ( n = 24). Mean reaction time averaged across the four ages was significantly faster for infants born to mothers in the 930 ( vs. 480) mg choline/d group. This result indicates that maternal consumption of approximately twice the recommended amount of choline during the last trimester improves infant information processing speed. Furthermore, for the 480-mg choline/d group, there was a significant linear effect of exposure duration (infants exposed longer showed faster reaction times), suggesting that even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.
Topics: Adult; Child Development; Choline; Dietary Supplements; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Mental Processes; Pregnancy; Pregnancy Trimester, Third; Visual Perception
PubMed: 29217669
DOI: 10.1096/fj.201700692RR -
Advances in Nutrition (Bethesda, Md.) Jan 2018
Topics: Adolescent; Adult; Child; Child, Preschool; Choline; Choline Deficiency; Diet; Female; Humans; Infant; Infant, Newborn; Liver Diseases; Male; Pregnancy; Recommended Dietary Allowances
PubMed: 29438456
DOI: 10.1093/advances/nmx004 -
Clinical Chemistry and Laboratory... Mar 2013
Topics: Aging; Choline; Dementia; Dietary Supplements; Humans; Risk Factors; Vascular Diseases; Vitamin B Complex
PubMed: 23449523
DOI: 10.1515/cclm-2013-0004 -
Nutrients Feb 2022Fetal alcohol spectrum disorder (FASD) is common and represents a significant public health burden, yet very few interventions have been tested in FASD. Cognitive... (Review)
Review
Fetal alcohol spectrum disorder (FASD) is common and represents a significant public health burden, yet very few interventions have been tested in FASD. Cognitive deficits are core features of FASD, ranging from broad intellectual impairment to selective problems in attention, executive functioning, memory, visual-perceptual/motor skills, social cognition, and academics. One potential intervention for the cognitive impairments associated with FASD is the essential nutrient choline, which is known to have numerous direct effects on brain and cognition in both typical and atypical development. We provide a summary of the literature supporting the use of choline as a neurodevelopmental intervention in those affected by prenatal alcohol. We first discuss how alcohol interferes with normal brain development. We then provide a comprehensive overview of the nutrient choline and discuss its role in typical brain development and its application in the optimization of brain development following early insult. Next, we review the preclinical literature that provides evidence of choline's potential as an intervention following alcohol exposure. Then, we review a handful of existing human studies of choline supplementation in FASD. Lastly, we conclude with a review of practical considerations in choline supplementation, including dose, formulation, and feasibility in children.
Topics: Child; Choline; Dietary Supplements; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Humans; Pregnancy; Vitamins
PubMed: 35277047
DOI: 10.3390/nu14030688 -
Nutrients Jul 2017Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects... (Meta-Analysis)
Meta-Analysis Review
Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (² = 84%, -value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality.
Topics: Adult; Aged; Betaine; Cardiovascular Diseases; Choline; Diet; Female; Humans; Male; Middle Aged; Prospective Studies; Risk; Risk Factors
PubMed: 28686188
DOI: 10.3390/nu9070711 -
Magnetic Resonance in Medicine Oct 2017To develop a novel diffusion-weighted magnetic resonance spectroscopy (DW-MRS) technique in conjunction with J-resolved spatially localized spectroscopy (JPRESS) to...
PURPOSE
To develop a novel diffusion-weighted magnetic resonance spectroscopy (DW-MRS) technique in conjunction with J-resolved spatially localized spectroscopy (JPRESS) to measure the apparent diffusion coefficients (ADCs) of brain metabolites beyond N-acetylaspartic acid (NAA), creatine (Cr), and choline (Cho) at 3T. This technique will be useful to probe tissue microstructures in vivo, as the various metabolites have different physiological characteristics.
METHODS
Two JPRESS spectra were collected (high b-value and low b-value), and the ADCs of 16 different metabolites were estimated. Two analysis pipelines were developed: 1) a 2D pipeline that uses ProFit software to extract ADCs from metabolites not typically accessible at 3T and 2) a 1D pipeline that uses TARQUIN software to extract the metabolite concentrations from each line in the 2D dataset, allowing for scaling as well as validation.
RESULTS
The ADCs of 16 different metabolites were estimated from within six subjects in parietal white matter. There was excellent agreement between the results obtained from the 1D and 2D pipelines for NAA, Cr, and Cho.
CONCLUSION
The proposed technique provided consistent estimates for the ADCs of NAA, Cr, Cho, glutamate + glutamine, and myo-inositol in all subjects and additionally glutathione and scyllo-inositol in all but one subject. Magn Reson Med 78:1235-1245, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Topics: Adult; Aspartic Acid; Brain; Choline; Creatine; Diffusion; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Phantoms, Imaging
PubMed: 27797114
DOI: 10.1002/mrm.26514