Diet-Induced High Serum Levels of Trimethylamine-N-oxide Enhance the Cellular Inflammatory Response without Exacerbating Acute Intracerebral Hemorrhage Injury in Mice.

Trimethylamine-N-oxide (TMAO), an intestinal flora metabolite of choline, may aggravate atherosclerosis by inducing a chronic inflammatory response and thereby promoting the occurrence of cerebrovascular diseases. Knowledge about the influence of TMAO-related inflammatory response on the pathological process of acute stroke is limited. This study was designed to explore the effects of TMAO on neuroinflammation, brain injury severity, and long-term neurologic function in mice with acute intracerebral hemorrhage (ICH). We fed mice with either a regular chow diet or a chow diet supplemented with 1.2% choline pre- and post-ICH. In this study, we measured serum levels of TMAO with ultrahigh-performance liquid chromatography-tandem mass spectrometry at 24 h and 72 h post-ICH. The expression level of P38-mitogen-protein kinase (P38-MAPK), myeloid differentiation factor 88 (MyD88), high-mobility group box1 protein (HMGB1), and interleukin-1ß (IL-1ß) around hematoma was examined by western blotting at 24 h. Microglial and astrocyte activation and neutrophil infiltration were examined at 72 h. The lesion was examined on days 3 and 28. Neurologic deficits were examined for 28 days. A long-term choline diet significantly increased serum levels of TMAO compared with a regular diet at 24 h and 72 h after sham operation or ICH. Choline diet-induced high serum levels of TMAO did not enhance the expression of P38-MAPK, MyD88, HMGB1, or IL-1ß at 24 h. However, it did increase the number of activated microglia and astrocytes around the hematoma at 72 h. Contrary to our expectations, it did not aggravate acute or long-term histologic damage or neurologic deficits after ICH. In summary, choline diet-induced high serum levels of TMAO increased the cellular inflammatory response probably by activating microglia and astrocytes. However, it did not aggravate brain injury or worsen long-term neurologic deficits. Although TMAO might be a potential risk factor for cerebrovascular diseases, this exploratory study did not support that TMAO is a promising target for ICH therapy.

Pathobiological Relationship of Excessive Dietary Intake of Choline/L-Carnitine: A TMAO Precursor-Associated Aggravation in Heart Failure in Sarcopenic Patients.

The microecological environment of the gastrointestinal tract is altered if there is an imbalance between the gut microbiota phylases, resulting in a variety of diseases. Moreover, progressive age not only slows down physical activity but also reduces the fat metabolism pathway, which may lead to a reduction in the variety of bacterial strains and bacteroidetes' abundance, promoting firmicutes and proteobacteria growth. As a result, dysbiosis reduces physiological adaptability, boosts inflammatory markers, generates ROS, and induces the destruction of free radical macromolecules, leading to sarcopenia in older patients. Research conducted at various levels indicates that the microbiota of the gut is involved in pathogenesis and can be considered as the causative agent of several cardiovascular diseases. Local and systematic inflammatory reactions are caused in patients with heart failure, as ischemia and edema are caused by splanchnic hypoperfusion and enable both bacterial metabolites and bacteria translocation to enter from an intestinal barrier, which is already weakened, to the blood circulation. Multiple diseases, such as HF, include healthy microbe-derived metabolites. These key findings demonstrate that the gut microbiota modulates the host's metabolism, either specifically or indirectly, by generating multiple metabolites. Currently, the real procedures that are an analogy to the symptoms in cardiac pathologies, such as cardiac mass dysfunctions and modifications, are investigated at a minimum level in older patients. Thus, the purpose of this review is to summarize the existing knowledge about a particular diet, including trimethylamine, which usually seems to be effective for the improvement of cardiac and skeletal muscle, such as choline and L-carnitine, which may aggravate the HF process in sarcopenic patients.

Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.

Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice.

Patients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.

Protective Effects of Black Raspberry (Rubus occidentalis) Extract against Hypercholesterolemia and Hepatic Inflammation in Rats Fed High-Fat and High-Choline Diets.

Choline is converted to trimethylamine by gut microbiota and further oxidized to trimethylamine-N-oxide (TMAO) by hepatic flavin monooxygenases. Positive correlation between TMAO and chronic diseases has been reported. Polyphenols in black raspberry (BR), especially anthocyanins, possess various biological activities. The objective of this study was to determine the effects of BR extract on the level of choline-derived metabolites, serum lipid profile, and inflammation markers in rats fed high-fat and high-choline diets. Forty female Sprague-Dawley (SD) rats were randomly divided into four groups and fed for 8 weeks as follows: CON (AIN-93G diet), HF (high-fat diet), HFC (HF + 1.5% choline water), and HFCB (HFC + 0.6% BR extract). Serum levels of TMAO, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and cecal trimethylamine (TMA) level were significantly higher in the HFC than in the HFCB. BR extract decreased mRNA expression of pro-inflammatory genes including nuclear factor-κB (NF-κB), interleukin (IL)-1ß, IL-6, and cyclooxygenase-2 (COX-2), and protein expression of NF-κB and COX-2 in liver tissue. These results suggest that consistent intake of BR extract might alleviate hypercholesterolemia and hepatic inflammation induced by excessive choline with a high-fat diet via lowering elevated levels of cecal TMA and serum TMAO in rats.

Effects of choline supplementation on liver biology, gut microbiota, and inflammation in Helicobacter pylori-infected mice.

AIMS: Diet is one of the factors affecting the pathogenicity of Helicobacter pylori (H. pylori) infection. Choline is a dietary component that is crucial for normal cellular function. However, choline intake imbalance can lead to liver injury, inflammation, and changes of the gut microbiota composition. The study aimed to explore the effects of choline supplementation on liver biology, gut microbiota, and inflammation in H. pylori-infected mice. MAIN METHODS: Liver function was detected by biochemical and histopathological analysis. Serum inflammatory markers were measured using ELISA. Fecal microbial profiles were determined via 16S rRNA sequencing. KEY FINDINGS: The results showed that choline supplementation decreased serum LDL level, while increased the activities of serum AST and ALT in normal BALB/c mice. Besides, choline also reduced hepatic SOD and GSH-Px activities, and elevated hepatic MDA level of H. pylori-infected mice. Moreover, choline markedly enhanced the concentrations of inflammatory factors including LPS, CRP, IL-6, TNF-α, and CXCL1 in H. pylori-infected mice. Meanwhile, choline and H. pylori cotreatment altered the richness and diversity of the mice gut microbiota, and increased the relative abundance of Escherichia_Shigella, which had a significant positive correlation with the levels of LPS, CRP, IL-6, TNF-α and CXCL1. SIGNIFICANCE: Our data suggest, for the first time, that choline can aggravate H. pylori-induced inflammation, which may be associated with the alterations of gut microbiota. This study may provide novel insights into the possible effects of food-derived choline on H. pylori infection-related diseases.

A high methyl donor diet affects physiology and behavior in Peromyscus polionotus.

Folic acid and other dietary methyl donors are widely supplemented due to their ability to prevent neural tube defects. Dietary methyl donors are also added to other consumables such as energy drinks due to energy-promoting attributes and other perceived benefits. However, there is mounting evidence that indicates developmental exposure to high levels of dietary methyl donors may have deleterious effects. We assessed whether behavior was affected in the social North American rodent species Peromyscus polionotus exposed to a diet enriched with folic acid, Vitamin B12, choline, and betaine/trimethylglycine(TMG). P. polionotus (PO) animals are very social and exhibit little repetitive behavior, particularly compared to their sister species, P. maniculatus. We assayed the effects of dietary methyl-donor supplementation on anxiety-like repetitive and social behaviors by testing young adult animals for novel cage behavior and in social interaction tests. Animals of both sexes exposed to the diet had increased repetitive behaviors and reduced social interactions. Males exposed to the diet became more aggressive compared to their control counterparts. Since methyl-diet animals were larger than control animals, DEXA scans and hormone analyses were performed. Animals exposed to the diet had increased body fat percentages and experienced hormonal changes typically associated with excess fat storage and anxiety-like behavior changes. Therefore, these data suggest the wide use of these dietary supplements makes further investigation imperative.

Improvement of Language in Children with Autism with Combined Donepezil and Choline Treatment.

The safety and efficacy of a novel combination treatment of AChE inhibitors and choline supplement was initiated and evaluated in children and adolescents with autism spectrum disorder (ASD). Safety and efficacy were evaluated on 60 children and adolescents with ASD during a 9-month randomized, double-blind, placebo-controlled trial comprising 12 weeks of treatment preceded by baseline evaluation, and followed by 6 months of washout, with subsequent follow-up evaluations. The primary exploratory measure was language, and secondary measures included core autism symptoms, sleep and behavior. Significant improvement was found in receptive language skills 6 months after the end of treatment as compared to placebo. The percentage of gastrointestinal disturbance reported as a side effect during treatment was higher in the treatment group as compared to placebo. The treatment effect was enhanced in the younger subgroup (younger than 10 years), occurred already at the end of the treatment phase, and was sustained at 6 months post treatment. No significant side effects were found in the younger subgroup. In the adolescent subgroup, no significant improvement was found, and irritability was reported statistically more often in the adolescent subgroup as compared to placebo. Combined treatment of donepezil hydrochloride with choline supplement demonstrates a sustainable effect on receptive language skills in children with ASD for 6 months after treatment, with a more significant effect in those under the age of 10 years.

Choline and Choline alphoscerate Do Not Modulate Inflammatory Processes in the Rat Brain.

Choline is involved in relevant neurochemical processes. In particular, it is the precursor and metabolite of acetylcholine (ACh). Choline is an essential component of different membrane phospholipids that are involved in intraneuronal signal transduction. On the other hand, cholinergic precursors are involved in ACh release and carry out a neuroprotective effect based on an anti-inflammatory action. Based on these findings, the present study was designed to evaluate the effects of choline and choline precursor (Choline alphoscerate, GPC) in the modulation of inflammatory processes in the rat brain. Male Wistar rats were intraperitoneally treated with 87 mg of choline chloride/kg/day (65 mg/kg/day of choline), and at choline-equivalent doses of GPC (150 mg/kg/day) and vehicle for two weeks. The brains were dissected and used for immunochemical and immunohistochemical analysis. Inflammatory cytokines (Interleukin-1ß, IL-1ß; Interleukin-6 , IL-6 and Tumor Necrosis Factor-α, TNF-α) and endothelial adhesion molecules (Intercellular Adhesion Molecule, ICAM-1 and Vascular cell Adhesion Molecule, VCAM-1) were studied in the frontal cortex, hippocampus, and cerebellum. The results clearly demonstrated that treatment with choline or GPC did not affect the expression of the inflammatory markers in the different cerebral areas evaluated. Therefore, choline and GPC did not stimulate the inflammatory processes that we assessed in this study.

Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH: a randomized controlled clinical trial.

Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease, is one of the most common hepatic diseases in children. We conducted a randomized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared with placebo. Participants were assigned to lifestyle modification plus placebo or lifestyle modification plus a mix containing docosahexaenoic acid, choline, and vitamin E (DHA-CHO-VE). Forty children and adolescents participated in the entire trial. The primary outcome was the improvement of liver hyperechogenicity. Secondary outcomes included alterations of alanine aminotransferase (ALT) and other metabolic parameters. Furthermore, changes of serum bile acids (BA) and plasma fibroblast growth factor 19 (FGF19) levels were evaluated as inverse biomarkers of disease severity. At the end of the study, we observed a significant decrease in severe steatosis in the treatment group (50% to 5%, p = 0.001). Furthermore, although the anthropometric and biochemical measurements in the placebo and DHA-CHO-VE groups were comparable at baseline, at the end of the study ALT and fasting glucose levels improved only in the treatment group. Finally, we found that BA levels were not influenced whereas FGF19 levels were significantly increased by DHA-CHO-VE. The results suggest that a combination of DHA, VE, and CHO could improve steatosis and reduce ALT and glucose levels in children with NASH. However, further studies are needed to assess the impact of a DHA and VE combination on repair of liver damage in paediatric NASH.

No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults.

Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2.0-2.5g of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. The null hypothesis that choline does not improve memory performance as compared to placebo was strongly supported by Bayesian statistics. These results are in contrast with animal studies suggesting that choline supplementation boosts memory performance and learning. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency 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 pancreatic insufficiency 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, 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 with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 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 increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption 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 group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Choline supplementation in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects. OBJECTIVE: Our primary goal was to determine whether postnatal choline supplementation has the potential to improve neurocognitive functioning, particularly hippocampal-dependent memory, in children with FASDs. DESIGN: The study was a double-blind, randomized, placebo-controlled pilot trial in children (aged 2.5-5 y at enrollment) with FASDs (n = 60) who received 500 mg choline or a placebo daily for 9 mo. Outcome measures were Mullen Scales of Early Learning (primary) and the elicited imitation (EI) memory paradigm (secondary). RESULTS: The administration proved feasible, and choline was well tolerated. Participants received a dose on 88% of enrolled days. The only adverse event linked to choline was a fishy body odor. Choline supplementation improved the secondary outcome (EI) only after immediate recall performance was controlled for, and the outcome was moderated by age. The treatment effect on EI items recalled was significant in the younger participants (2.5- to ≤4.0-y-olds); the young choline group showed an increase of 12-14 percentage points greater than that of the young placebo group on delayed recall measures during treatment. However, there was a marginal baseline difference in delayed item recall between the young choline and placebo groups as well as a potential ceiling effect for item recall, both of which likely contributed to the observed treatment effect. We also observed a trend toward a negative effect of choline supplementation on the immediate EI recall of ordered pairs; the young placebo group showed an increase of 8-17 percentage points greater than that of the choline group during treatment. There was an inverse relation between choline dose (in mg/kg) and memory improvement (P = 0.041); the data suggest that weight-adjusted doses may be a better alternative to a fixed dose in future studies. Limitations included trend-level baseline differences in performance, the post-hoc determination of age moderation, and potential ceiling effects for the memory measure. CONCLUSIONS: This pilot study suggests that an additional evaluation of choline supplementation as an intervention for memory functioning in children with FASDs is warranted. The observed interaction between age and choline's effect on EI suggests that potential sensitive periods should be considered in future work. This trial was registered at clinicaltrials.gov as NCT01149538.

Myricetin derived from Hovenia dulcis Thunb. ameliorates vascular endothelial dysfunction and liver injury in high choline-fed mice.

The present study was conducted to explore the protective effects of myricetin (MYR) purified from Hovenia dulcis Thunb. against vascular endothelial dysfunction and liver injury in mice fed with 3% dietary choline water. MYR was shown to possess strong scavenging activities against DPPH˙, HO˙, and O2˙(-) and ferric-reducing antioxidant power in vitro. Mice fed 3% dietary choline water for 8 weeks significantly displayed vascular endothelial dysfunction and liver oxidative stress (p < 0.01). Furthermore, continuous administration of MYR at 400 and 800 mg per kg bw in choline-fed mice could significantly decrease the high choline diet-induced elevation of serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), endothelin 1 (ET-1) and thromboxane A2 (TXA2) levels as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, while the choline-induced decline of serum high density lipoprotein-cholesterol (HDL-C), endothelin nitric oxide synthase (eNOS), nitric oxide (NO) and prostaglandin I2 (PGI2) levels could be markedly elevated in mice (p < 0.05, p < 0.01). Meanwhile, MYR at 400 and 800 mg per kg bw also increased hepatic total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities and decreased hepatic malonaldehyde (MDA) and non-esterified fatty acid (NEFA) levels in mice, relative to choline-treated mice (p < 0.05, p < 0.01). These results together with conventional haematoxylin and eosin (H&E) and Oil Red O staining observation of the liver and vascular tissues suggested that MYR exerted a significant protective role against high choline diet-induced endothelial dysfunction and liver injury in mice. This is the first report showing that high intake of dietary choline can induce liver damage and that MYR can ameliorate choline-induced vascular endothelial dysfunction and liver injury.

Choline associated hypersexuality in a 79-year-old man.

Hypersexuality, also referred to as sexually inappropriate behavior and sexual disinhibition, involves persistent, uninhibited sexual behaviors directed at oneself or at others, sometimes associated with neurodegenerative disorders. Choline is a water-soluble essential nutrient, used as a dietary supplement in different diseases. This report was aimed at considering choline intake as a possible cause of iatrogenic hypersexuality. After an evaluation, a 79-year-old man affected by memory loss was diagnosed with mild cognitive impairment and treated with oral choline. After 6 weeks of regular choline assumption, the patient showed a pathological increase in libido with sexual urges. As choline was withdrawn, the hypersexuality disappeared within 5 days. Since hypersexuality may be an underreported and overlooked adverse effect of drugs and dietary supplements acting on the cholinergic pathway, this should be considered when treating and counselling patients with inappropriate sexual behavior.

The effects of α-lipoic acid on liver oxidative stress and free fatty acid composition in methionine-choline deficient diet-induced NAFLD.

Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial steatosis and subsequent oxidative stress. The aim of this study was to examine the effects of α-lipoic acid (LA) on methionine-choline deficient (MCD) diet-induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups (n=7 per group): (1) control fed with standard chow, (2) MCD2 group--fed with MCD diet for 2 weeks, and (3) MCD2+LA group--2 weeks on MCD receiving LA i.p. 100 mg/kg/day. After the treatment, liver samples were taken for pathohistology, oxidative stress parameters, antioxidative enzymes, and liver free fatty acid (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group, while it was reduced to single fat droplets evident in MCD2+LA group. Lipid peroxidation and nitrosative stress were increased by MCD diet, while LA administration induced a decrease in liver malondialdehyde and nitrates+nitrites level. Similary, LA improved liver antioxidative capacity by increasing total superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic acid (DHA), while LA treatment increased their proportions. It can be concluded that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced hepatic steatosis through an increase in SOD activity and GSH level. In addition, LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory and antioxidant effects of LA in MCD diet-induced NAFLD.

Breast milk choline contents are associated with inflammatory status of breastfeeding women.

BACKGROUND: Choline is an important component of human breast milk and its content varies considerably among breastfeeding women and lactation periods. OBJECTIVE: The aim of this study was to assess the relationship between breast milk choline contents and inflammatory status in breastfeeding women. METHODS: Breast milk choline compounds and serum C-reactive protein (CRP) concentrations were determined in breastfeeding women at 1 to 3 (n = 53) or 22 to 180 (n = 54) days postpartum, expressing colostrum or mature milk, respectively. RESULTS: Median concentrations of free choline, phosphocholine, glycerophosphocholine, phospholipid-bound choline, and total choline were 71, 38, 96, 194, and 407 µmol/L or 93, 351, 958, 186, and 1532 µmol/L in colostrum or mature milk, respectively. Median serum CRP concentrations were 4.13 mg/L and 0.33 mg/L at 1 to 3 days and 22 to 180 days postpartum, respectively. At 1 to 3 days postpartum, milk free choline, phosphocholine, glycerophosphocholine, and total choline as well as serum CRP concentrations were significantly higher in breastfeeding women who delivered by cesarean section than those who delivered via the vaginal route. Serum CRP concentration was positively correlated with colostrum free choline (r = 0.703; P < .001), phosphocholine (r = 0.759; P < .001), glycerophosphocholine (r = 0.706; P < .001), and total choline (r = 0.693; P < .001), whereas it was negatively correlated (r = -0.442; P < .001) with colostrum phospholipid-bound choline. Serum CRP was also negatively correlated with mature milk free choline (r = -0.278; P < .05), but no correlation was found between serum CRP and other choline compounds in mature milk. CONCLUSION: These data show that the concentrations of milk choline compounds are associated with inflammatory status of breastfeeding women, particularly during the first few days after delivery.

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability.

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway.

Dandelion leaf extract protects against liver injury induced by methionine- and choline-deficient diet in mice.

We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine- and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH). C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight·daily (MCD+D200), and MCD diet supplemented with EDL at 500 mg/kg body weight·daily (MCD+D500). Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-α and IL-6; and levels of caspase-3 and pJNK/JNK protein. Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH. Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-α, and IL-6; on the contrary, the levels of reduced GSH increased. At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK. These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities.

[The experience with the topical application of non-steroidal anti-inflammatory agents for the treatment of otitis media].

The objective of the present study was to estimate the therapeutic efficacy and safety of the topically applied otinum ear drops. The authors present the results of the combined treatment of acute catarrhal otitis in the children with the use of choline salicilate (otinum). The study included 50 patients randomized into two identical groups. The children of group 1 received systemic therapy supplemented by the topical application of otinum, those in group 2 were prescribed a 3% alcoholic solution of boric acid. The study has demonstrated a significantly more pronounced positive dynamics of clinical conditions in the patients of group 1 compared with those of the control group. The total duration of therapy in the first group was 37.5% shorter than in the second. The results of the study confirmed the strong anti-inflammatory and analgesic action of choline salicilate. The pain was relieved within 7 minutes on the average after the application of this agent. It is concluded that otinum can be recommended for the introduction into combined therapy of acute catarrhal otitis media as an efficacious anti-inflammatory and analgetic drug.