Figure 1
Schematic of the inter-relation of choline with the methionine- homocysteine cycle. Reactions catalyzed by: 1 ) methionine adenosyltransferase, 2 ) phosphatidylethanolamine- N -methyltransferase (PEMT), 3 ) choline oxidase, 4 ) betaine aldehyde dehydrogenase, 5 ) betaine homocysteine methyltransferase (BHMT), 6 ) SAH hydrolase, 7 ) cystathionine b synthase, 8 ) 5-methyltetra- hydrofolate homocysteine methyltransferase (methionine synthase), and 9 ) 5, 10 methylene tetrahydrofolate reductase (MTHFR).
Source publication
Cystic fibrosis (CF) is associated with many clinical complications including steatosis for which the relation to defective CF transmembrane conductance regulator protein is unclear. Choline deficiency results in hepatic steatosis. Choline is the precursor of betaine, which donates methyl groups for remethylation of homocysteine to methionine and d...
Contexts in source publication
Context 1
... role as a component of phosphatidylcholine, thus functioning in membrane lipids, lipoproteins, bile lipid, and lung surfactant, in the neurotransmitter acetylcholine, and as a precursor to betaine, which functions as a source of labile methyl groups (12). The metabolism of choline intersects with the methionine- homocysteine cycle at 2 steps (Fig. 1). The sequential transfer of methyl groups from S-adenosylmethionine (SAM) to phospha- tidylethanolamine by phosphatidylethanolamine-N-methyl trans- ferase (PEMT) leads to de novo synthesis of choline in phosphatidylcholine (PC) (13). PC can also be formed via cytidine diphosphocholine, but this pathway requires preformed choline ...
Context 2
... homocysteine involves 5,10- methylenetetrahydrofolate reductase (MTHFR) and methionine synthase, and is usually considered the major pathway. In the folate-independent pathway, betaine-homocysteine S-methyl- transferase (BHMT) transfers methyl groups from betaine to homocysteine to regenerate methionine with dimethylglycine as the other product ( Fig. 1) (15). Betaine is synthesized from choline by choline oxidase and betaine adehyde dehydrogenase. Further metabolism of dimethylglycine generates two 1-carbon units, thereby recovering all 3 methyl groups donated from SAM to form choline (16,17). The MTHFR and BHMT pathways show reciprocal interaction such that choline oxidase and BHMT ...
Context 3
... The meta- bolism of choline intersects with the methionine-homocysteine cycle at the de novo synthesis of choline, in which the sequential methylation of phosphatidylethanolamine with methyl groups derived from methionine via SAM, catalyzed by PEMT, leads to the formation of PC, and through the betaine-dependent remethylation of homocysteine (Fig. 1). An increase in SAM: SAH in children with CF, as shown in Innis et al. (26; Table 1), can result in reduced activity of several methyltransferases, including PEMT (14,33), which raises the possibility that de novo synthesis of choline is reduced in CF secondary to the increased homocysteine and decreased SAM:SAH. Possible explanations ...
Similar publications
Previous studies showed that chronic ethanol administration alters methionine metabolism in the liver, resulting in increased intracellular S-adenosylhomocysteine (SAH) levels and increased homocysteine release into the plasma. We showed further that these changes appear to be reversed by betaine administration. This study compared the effects of b...
Background:
Previous studies indicated that nonpurified and purified commercially available control murine diets have different metabolic effects with potential consequences on hepatic methionine metabolism and liver histology.
Methods:
We compared the metabolic and histological effects of commercial nonpurified (13% calories from fat; 57% calor...
Citations
... Homocysteine rises when remethylation is limiting. 44 Choline, sarcosine, glycine, and serine, which furnish labile methyl groups for the remethylation of homocysteine, were not well differentiated in kwashiorkor and marasmic-kwashiorkor, relative to other participants ( Table 2). In contrast, betaine, a methyl donor and intracellular osmolyte, was notably higher in kwashiorkor (P = 0¢047) and marasmickwashiorkor (P < 0¢0001), relative to controls ( Table 2). ...
Background
Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children.
Methods
Blood was collected from children aged 12–60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups.
Findings
Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor.
Interpretation
Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation.
Funding
The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.
... The samples were then shipped to the University of CaliforniaeDavis for processing and data were sent to the University of CaliforniaeSan Diego and Emory University. Estimates of maternal choline, betaine, and DMG were obtained using a UPLC-Micro triplequad MS/MS (Waters, Micromass) using modified Holms' procedures (Holm, Ueland, Kvalheim, & Lien, 2003;Innis & Hasman, 2006). Change in choline and its metabolites, betaine and dimethylglycine (DMG), were computed by subtracting baseline concentrations from levels obtained at the second visit. ...
The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) on attentional regulation skills was explored in a randomized clinical trial conducted in Ukraine. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to one of three groups (No study-provided supplements, Multivitamin/Mineral Supplement (MVM), or MVM plus Choline). Their offspring were seen in the preschool period and a reaction time task was administered. Participants were asked to press a response button as quickly as possible as thirty stimuli from the same category (animals) were presented consecutively and then followed by 6 stimuli from a novel category (vehicles). Number correct, mean latency of the response over trials, and variability in the latency were analyzed separately by sex. During the initial animal trials, boys whose mothers received MVM during pregnancy had more correct responses and reduced response latency compared to boys whose mothers had no MVM treatment. During vehicle trials, maternal choline supplementation was associated with increased response speed in males without a PAE history. Females receiving supplements did not show the same benefits from micronutrient supplementation and were more adversely impacted by prenatal alcohol exposure. Relationships between maternal levels of choline, betaine, and dimethylglycine (DMG) and task performance were also assessed. Although no effects were found for choline after adjusting for multiple comparisons, lower baseline DMG level was associated with greater accuracy and shorter latency of responses in the initial animal trials and shorter latency in the vehicle trials in female preschoolers. Level of betaine in Trimester 3 was associated with reduced variability in the latency of male responses during the animal trials. Maternal micronutrient supplementation in pregnancy appears to improve preschool reaction time performance but the effects varied as a function of sex and PAE exposure status.
... 5-Oxoproline was quantified by LC-MS/MS, as described previously (21). Choline, betaine, dimethylglycine (DMG), methionine, cysteine, and total homocysteine were analyzed by HPLC-MS/MS as previously described in detail by Friesen et al. (21) and Innis and Hasman (22). ...
Background:
Recently, we showed that there are higher protein, lysine, and phenylalanine requirements in late stages of pregnancy compared with early stages. Animal studies have suggested an increased dietary need for specific dispensable amino acids in pregnancy; whether such a need exists in human pregnancies is unknown.
Objective:
The objective of the current study was to examine whether healthy pregnant women at midgestation (20-29 wk) and late gestation (30-40 wk) have a dietary demand for glycine, a dispensable amino acid, using the indicator amino acid oxidation method and measurement of plasma 5-oxoproline concentrations.
Methods:
Seventeen healthy women (aged 26-36 y) randomly received different test glycine intakes (range: 5-100 mg·kg-1·d-1) during each study day in midgestation (∼26 wk, n = 17 observations in 9 women) and late gestation (∼35 wk, n = 19 observations in 8 women). Diets were isocaloric with energy at 1.7 × resting energy expenditure. Protein was given as a crystalline amino acid mixture based on egg protein composition at current estimated average requirement (EAR; 0.88 g·kg-1·d-1). Breath samples were collected at baseline and isotopic steady state to measure oxidation of L-[1-13C]phenylalanine to 13CO2 (F13CO2). Plasma was collected at the sixth hour of the study day. Linear regression crossover analysis and simple linear regression were used to assess responses in F13CO2 and plasma 5-oxoproline concentrations to different glycine intakes.
Results:
No statistically significant responses were observed in midgestation. However, in late gestation, lower glycine intakes resulted in higher rates of F13CO2 (suggesting low protein synthesis) with a breakpoint for phenylalanine oxidation at >37 mg glycine·kg-1·d-1 and higher plasma 5-oxoproline (suggesting low glycine availability) with a breakpoint >27 mg glycine·kg-1·d-1.
Conclusions:
The findings suggest that glycine should be considered a "conditionally" indispensable amino acid during late gestation, especially when protein intakes are at 0.88 g·kg-1·d-1, the current EAR. This trial was registered at clinicaltrials.gov as NCT02149953.
... (p = 0.0137). At V5 (d49 (45)(46)(47)(48)(49)(50)(51)) there was no improvement seen yet (69.9 [60.1-82.5]%). Similarly, forced vital capacity (FVC) and forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75) increased, with median improvements of 5.4 (−0.3-8.2)% and 7.6 (−0.8-8.4)%, ...
... We further investigated whether choline supplementation increased plasma PC concentration and influenced its metabolism in these patients. Endogenous plasma PC concentration prior to choline supplementation was 1.00 (0.85-1.19) mmol/L, and was not altered after 49 (45)(46)(47)(48)(49)(50)(51) Figure 6A shows that the molecular composition of plasma PC was identical prior to (white panels) and after (black panels) choline supplementation, with PC containing an oleic (C18 De novo PC synthesis, reflected by D9-PC [13,27], resulted in preferential synthesis of C18:1-D9-PC and C18:2-D9-PC ( Figure 6A, grey panels). By contrast, PC synthesis via the methylation of phosphatidylethanolamine, resulting in D3-PC by using (D9-)betaine for the synthesis of D3methionine as a methyl donor [13,27] (Figure 6A, dotted panels), was preferential for the synthesis of PC containing an arachidonic (C20:4-D3-PC) and docosahexaenoic acid residue (C22:6-D3-PC). ...
... We further investigated whether choline supplementation increased plasma PC concentration and influenced its metabolism in these patients. Endogenous plasma PC concentration prior to choline supplementation was 1.00 (0.85-1.19) mmol/L, and was not altered after 49 (45)(46)(47)(48)(49)(50)(51) Figure 6A shows that the molecular composition of plasma PC was identical prior to (white panels) and after (black panels) choline supplementation, with PC containing an oleic (C18:1-PC), linoleic (C18:2-PC) or arachidonic (C20:4-PC) acid residue dominating over PC containing docosahexaenoic acid (C22:6-PC). ...
Background: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. Methods: 10 adult male CF patients were recruited (11/2014–1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84–91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D9]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. Results: Supplementation increased plasma choline from 4.8 (4.1–6.2) µmol/L to 10.5 (8.5–15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D9-labeled PC was decreased (12.2 [10.5–18.3] µmol/L vs. 17.7 [15.5–22.4] µmol/L, p < 0.01), indicating D9-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9–74.8)% to 78.3 (60.1–83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37–8.82)% to 0.84 (0.56–1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. Conclusions: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.
... Plasma concentrations of free choline, betaine and dimethylglycine were quantified by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) as described [17,21], using a Waters Iclass ACQUITY UPLC system connected to a Quattro Micro tandem MS configured with an electrospray source (Waters Corporation, Milford, MA, USA). The LC was equipped with a pre-column (2.1 × 12.1 mm) and a column (2.1 × 150 mm), both Zorbax Rx-SIL with a particle size of 5 μm (Agilent Technologies, Santa Clara, CA, USA). ...
Background:
Plasma concentrations of choline and its metabolites might serve as biomarkers for the health outcomes of several pathological states such as cardiovascular disease and cancer. However, information about the reliability of biomarkers of choline status is limited. We investigated biological variations in repeated measures of choline and metabolites in healthy adults to assess them as biomarkers.
Methods:
Blood samples were collected after an overnight fast at three-time points 12 days apart from 40 adults (mean age, 33 y; male, n = 21). A subset (n = 19; [male, n = 8]) provided one additional sample after a breakfast meal. Plasma free choline, betaine and dimethylglycine were measured using liquid chromatography-tandem mass spectrometry, and plasma phosphatidylcholine, sphingomyelin and lysophosphatidylcholine were measured using high-performance liquid chromatography.
Results:
The biological variations observed for choline and metabolites were ≤ 13% for adult fasting samples. This corresponded to intra-class correlations (ICC) that ranged from 0.593 to 0.770 for fasting values for choline and metabolites. A similar ICC range was also obtained between fasting and post-prandial states. Although most post-prandial concentrations of choline and metabolites were significantly higher (P < .05) than fasting, all fell within a calculated reference interval. The participants were correctly classified in tertiles for fasting and post-prandial states for choline (68%) and metabolites (range = 32% phosphatidylcholine and 79% for sphingomyelin).
Conclusions:
These findings indicate that biological variations of choline and metabolites are low in healthy adults and values from a single blood sample can be used as a biomarker. However, choosing phosphatidylcholine as a biomarker is less reliable.
... Plasma was separated by centrifugation (2000 × g; 15 min; 4°C) within 20 min, placed into aliquots, and stored at −70°C until later analysis. Plasma free choline, betaine, and dimethylglycine concentrations were quantified by stable isotope dilution LC-tandem MS, as described previously (24). All CVs were <5%. ...
Background:
Choline is an important nutrient during development. However, there are limited data on dietary choline intake and status in toddlers and the relation to neurodevelopmental outcomes.
Objective:
This study assessed dietary choline intake and status in healthy toddlers at ages 1 and 2 y and determined the relation to neurodevelopmental outcomes.
Methods:
This is a secondary analysis of data from healthy toddlers enrolled in a double-blind, randomized controlled trial of long-chain polyunsaturated fatty acid supplementation between ages 1 and 2 y. Dietary intakes of betaine and choline were estimated by 3-d food records; plasma free choline, betaine, and dimethylglycine were quantified by liquid chromatography-tandem mass spectrometry. Developmental outcomes were assessed at age 2 y with the use of the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), Cognitive and Language composites, and the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI).
Results:
The mean ± SD daily intake for total choline at age 1 y was 174 ± 56.2 mg/d and increased (P < 0.001) to 205 ± 67.5 mg/d at age 2 y. At ages 1 and 2 y, 71.8% and 55.8%, respectively, of toddlers did not meet the recommended 200-mg/d Adequate Intake (AI) for dietary choline. At age 1 y, mean ± SD plasma free choline, betaine, and dimethylglycine concentrations were 10.4 ± 3.3, 41.1 ± 15.4, and 4.1 ± 1.9 µmol/L, respectively. Plasma free choline (8.5 ± 2.3 µmol/L) and dimethylglycine (3.2 ± 1.3 µmol/L) concentrations were lower (P < 0.001) at age 2 y. Plasma betaine concentrations were positively associated with the Beery-VMI (β = 0.270; 95% CI: 0.026, 0.513; P = 0.03) at age 2 y.
Conclusions:
These findings suggest that most toddlers are not meeting the recommended AI for dietary choline and that higher plasma betaine concentrations are associated with better visual-motor development at age 2 y. Further work is required to investigate choline metabolism and its role in neurodevelopment in toddlers. The trial is registered at clinicaltrials.gov as NCT01263912.
... [6,7] Amino acid metabolism is complex and involves various micronutrients such as choline, folic acid and vitamin B 12 . Choline depletion and elevated vitamin B 12 concentrations have been described in children with CF. [8,9] Little is known about the effect of choline supplementation on amino acid status, particularly in the CF care setting where the daily intake from CF-specific vitamin products results in serum vitamin B 12 concentrations that are relatively high. [10] In a study by Innis et al [11], high dose choline supplementation for two weeks in children with CF improved choline status, reduced plasma homocysteine and increased methionine concentrations. ...
... Choline (μmol/L) was quantified from calibration curves generated from reference materials (SigmaAldrich-Fluka, St. Louis, MO) of choline chloride (50-1.6 μM) spiked with identical amount of internal standard compound as the plasma extracts. The calibration standards and plasma extracts were assayed as previously reported [8] using a Waters AcquityTM UPLC system/AB Sciex 5500 mass spectrometer at 0.5 mL/minute flow of 81:19 (v/v) acetonitrile: 15 mM ammonium formate with the addition of a 60:40 (v/v) acetonitrile: 15 mM ammonium formate mobile phase to elute the more polar GPC and CDPC compounds from an Agilent RX-Sil (2.1 × 50 mm, 1.8 μm particle size) column. ...
The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children, ages 5 to 18 years, with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB™, LXS) or placebo with similar calorie and fat content. Plasma amino acids were measured at baseline, 3, and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most subjects. Alanine and cysteine were elevated in 24% and 36% of subjects, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared to placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LXS did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI.
... Free choline and betaine were assayed in the Innis lab as detailed in Innis and Hassman [28]. Twenty µL of milk was transferred to a 1.5 mL Eppendorf tube containing 10 µL of internal standards, deuterium labeled free choline, and vortexed. ...
... Visual inspection of the continuous data and review of the literature e.g., [33] provided support for sensor clusters of interest. Data were averaged across sensor groups as follows (see Figure 1): FrontalZ (4,10,11,16,18,19), FrontalL (24,27,28,34,33), FrontalR (116, 117, 122, 123, 124), CentralZ (7, 31, 55, 80, 106, REF), ParietalZ (61, 62, 67, 72, 77, 78), and Midline (6,11,15,16,55,REF). Clusters were individually assessed for mean amplitude, peak amplitude, and latency to peak amplitude within the 200 to 900 ms window for each condition using NetStation 4.5.4 ...
... Sensor map showing the clusters used in analyses: FrontalZ(4,10,11,16,18,19), FrontalL(24,27,28,34,33), FrontalR (116, 117, 122, 123, 124), CentralZ(7,31,55, 80, 106, REF), ParietalZ(61,62, 67, 72, 77, 78), and Midline(6,11,15,16,55, REF). ...
The aim was to explore the relation of human milk lutein; choline; and docosahexaenoic acid (DHA) with recognition memory abilities of six-month-olds. Milk samples obtained three to four months postpartum were analyzed for fatty acids, lutein, and choline. At six months, participants were invited to an electrophysiology session. Recognition memory was tested with a 70-30 oddball paradigm in a high-density 128-lead event-related potential (ERP) paradigm. Complete data were available for 55 participants. Data were averaged at six groupings (Frontal Right; Frontal Central; Frontal Left; Central; Midline; and Parietal) for latency to peak, peak amplitude, and mean amplitude. Difference scores were calculated as familiar minus novel. Final regression models revealed the lutein X free choline interaction was significant for the difference in latency scores at frontal and central areas (p < 0.05 and p < 0.001; respectively). Higher choline levels with higher lutein levels were related to better recognition memory. The DHA X free choline interaction was also significant for the difference in latency scores at frontal, central, and midline areas (p < 0.01; p < 0.001; p < 0.05 respectively). Higher choline with higher DHA was related to better recognition memory. Interactions between human milk nutrients appear important in predicting infant cognition, and there may be a benefit to specific nutrient combinations.
... The folate independent remethylation of Hcy to methionine, catalysed by BHMT, uses betaine as the methyl donor (Fig. 6A). Betaine is exclusively and irreversibly catabolised by BHMT to generate dimethylglycine (DMG) [36], and the ratio of the hepatic concentration of betaine:DMG can be taken as a measure of the activity of this pathway [13,21,32]. We therefore determined the concentrations of BHMT and DMG in liver samples from Wt and Nox4 -/mice by mass spectrometry. ...
Glutathione is the major intracellular redox buffer in the liver and is critical for hepatic detoxification of xenobiotics and other environmental toxins. Hepatic glutathione is also a major systemic store for other organs and thus impacts on pathologies such as Alzheimer's disease, Sickle Cell Anaemia and chronic diseases associated with aging. Glutathione levels are determined in part by the availability of cysteine, generated from homocysteine through the transsulfuration pathway. The partitioning of homocysteine between remethylation and transsulfuration pathways is known to be subject to redox-dependent regulation, but the underlying mechanisms are not known. An association between plasma Hcy and a single nucleotide polymorphism within the NADPH oxidase 4 locus led us to investigate the involvement of this reactive oxygen species- generating enzyme in homocysteine metabolism. Here we demonstrate that NADPH oxidase 4 ablation in mice results in increased flux of homocysteine through the betaine-dependent remethylation pathway to methionine, catalysed by betaine-homocysteine-methyltransferase within the liver. As a consequence NADPH oxidase 4-null mice display significantly lowered plasma homocysteine and the flux of homocysteine through the transsulfuration pathway is reduced, resulting in lower hepatic cysteine and glutathione levels. Mice deficient in NADPH oxidase 4 had markedly increased susceptibility to acetaminophen-induced hepatic injury which could be corrected by administration of N-acetyl cysteine. We thus conclude that under physiological conditions, NADPH oxidase 4-derived reactive oxygen species is a regulator of the partitioning of the metabolic flux of homocysteine, which impacts upon hepatic cysteine and glutathione levels and thereby upon defence against environmental toxins.
... Suboptimal choline status with decreased plasma concentrations and related metabolic changes have been reported in children and adults with cystic fibrosis (CF) and pancreatic insufficiency (PI) treated with pancreatic enzyme medications [1][2][3][4][5] . Factors contributing to suboptimal choline status in CF include lower dietary intake and persistent malabsorption of dietary and biliary phosphatidylcholine 1-3;5-9 . ...
Background:
Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency (PI) in spite of enzyme treatment and may result in liver, fatty acid and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB [LXS]) to improve choline status.
Methods:
Children with CF and PI were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption (CFA), pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared to a healthy comparison group matched for age, sex and body size.
Results:
110 subjects were enrolled (age 10.4 ± 3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine (PC) increased and fecal PC/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% CFA increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident.
Conclusions:
LXS had improved choline intake, plasma choline status and muscle choline stores, compared with placebo. The choline-rich supplement was safe, accepted by participants and improved choline status in children with CF.
