Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice.

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.

Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis.

Betaine is used to lower elevated plasma homocysteine levels, which are a risk factor for cardiovascular diseases (CVD). However, some studies have shown that betaine may have a negative effect on blood lipids. Betaine supplementation is becoming more and more common, but the relationship between betaine supplementation and blood lipoprotein levels are unclear. The purpose of the study described here was thus to perform a meta-analysis of randomized placebo-controlled trials on the effects of betaine supplementation at a daily dose of at least 4 g on blood lipids in adults. Six randomized controlled trials published between 2002 and 2018 were identified. All six studies used adult participants supplemented with at least 4 g/d of betaine for six to twenty-four weeks. A meta-analysis was carried out using a random-effects model, and the overall effect size was calculated for changes in plasma total cholesterol (TC), HDL cholesterol, LDL cholesterol, and triglycerides (TG). The pooled estimate of the effects of betaine supplementation compared to placebo on TC was 0.34 mmol/L (95% CI: 0.02, 0.65), p = 0.0352. No significant effect was observed for LDL, HDL, or TG. Supplementation with at least 4 g/d of betaine for a minimum of six weeks may moderately increase plasma TC, which might be important in the context of cardiovascular health.

Effect of Betaine on Reducing Body Fat-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Animal studies have shown the beneficial effect of betaine supplementation on reducing body fat, while the data from human studies are controversial and inconsistent. The objective of the present systematic review was to investigate the effects of betaine intervention on treating obesity in humans and quantitatively evaluate the pooled effects based on randomized controlled trials with a meta-analysis. The PubMed and Scopus databases, and the Cochrane Library, were searched up to September 2019. Weighted mean differences were calculated for net changes in obesity-related indices by using a random-effects model. Publication bias was estimated using Begg's test. Six studies with 195 participants were identified. Betaine supplementation significantly reduced the total body fat mass (-2.53 kg; 95% CI: -3.93, -0.54 kg; I2 = 6.6%, P = 0.36) and body fat percentage (-2.44%; 95% CI: -4.20, -0.68%; I2 = 0.0%, P = 0.44). No changes were observed regarding body weight (-0.29 kg; 95% CI: -1.48, 0.89 kg; I2 = 0.00%, P = 0.99) and body mass index (-0.10 kg/m2; 95% CI: -5.13, 0.31 kg/m2; I2 = 0.00%, P = 0.84). The results suggested that dietary betaine supplementation might be an effective approach for reducing body fat.

Betaine Supplementation Enhances Lipid Metabolism and Improves Insulin Resistance in Mice Fed a High-Fat Diet.

Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver disease, certain cancers, and insulin resistance. However, there are no effective drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally occurring molecule. This study shows that dietary betaine supplementation significantly inhibits the white fat production in a high-fat diet (HFD)-induced obese mice. This might be due to betaine preventing the formation of new white fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial biogenesis and promoting browning of WAT. Furthermore, dietary betaine supplementation decreases intramyocellular lipid accumulation in HFD-induced obese mice. Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance. Together, these findings could suggest that inhibiting WAT production, intramyocellular lipid accumulation and inflammation, betaine supplementation limits HFD-induced obesity and improves insulin resistance.

Occupational contact allergy to cocamidopropyl betaine and its impurities.

BACKGROUND: Contact allergy to cocamidopropyl betaine has been attributed to its impurities dimethylaminopropylamine and cocamidopropyl dimethylamine. OBJECTIVES: To describe patients with positive patch test reactions to cocamidopropyl betaine-related compounds in an occupational dermatology clinic. METHODS: We reviewed the 2002-2009 patch test records at the Finnish Institute of Occupational Health for allergic reactions to cocamidopropyl betaine, dimethylaminopropylamine, cocamidopropyl dimethylamine, and oleamidopropyl dimethylamine. Results. Irritant reactions to at least one of the test substances were seen in 39% of the 1092 patients tested. Fifteen (1.3%) patients showed allergic reactions: 13 to cocamidopropyl dimethylamine, 11 to dimethylaminopropylamine, 8 to oleamidopropyl dimethylamine, and 2 to cocamidopropyl betaine. Concomitant reactions to cocamidopropyl dimethylamine, dimethylaminopropylamine and oleamidopropyl dimethylamine were common. Ten of the 15 patients were diagnosed with occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds. The sources of occupational exposure included hair care products, hair colours, perm wave solutions, and liquid soaps. Multiple contact allergies and exposure to several irritant factors were common, and all patients had hand eczema. CONCLUSIONS: Patch test reactions to cocamidopropyl betaine-related compounds are difficult to interpret, owing to extremely common irritant reactions. Cocamidopropyl betaine itself is probably not an allergen. Occupational allergic contact dermatitis caused by cocamidopropyl betaine-related compounds is relatively rare and, unlike non-occupational cocamidopropyl betaine-related allergy, typically manifests as hand dermatitis.

Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes.

Developmental epigenetic changes, such as DNA methylation, have been recognized as potential pathogenic factors in inflammatory bowel diseases, the hallmark of which is an exaggerated immune response against luminal microbes. A methyl-donor (MD) diet can modify DNA methylation at select murine genomic loci during early development. The components of the MDs are routinely incorporated into prenatal human supplements. Therefore, we studied the effects of maternal MD supplementation on offspring colitis susceptibility and colonic mucosal DNA methylation and gene expression changes in mice as a model. Additionally, we investigated the offspring mucosal microbiomic response to the maternal dietary supplementation. Colitis was induced by dextran sulfate sodium. Colonic mucosa from offspring of MD-supplemented mothers following reversal to control diet at weaning was interrogated by methylation-specific microarrays and pyrosequencing at postnatal days 30 (P30) and P90. Transcriptomic changes were analyzed by microarray profiling and real-time reverse transcription polymerase chain reaction. The mucosal microbiome was studied by high throughput pyrosequencing of 16S rRNA. Maternal MD supplementation induced a striking susceptibility to colitis in offspring. This phenotype was associated with colonic mucosal DNA methylation and expression changes. Metagenomic analyses did not reveal consistent bacteriomic differences between P30 and P90, but showed a prolonged effect of the diet on the offspring mucosal microbiome. In conclusion, maternal MD supplementation increases offspring colitis susceptibility that associates with persistent epigenetic and prolonged microbiomic changes. These findings underscore that epigenomic reprogramming relevant to mammalian colitis can occur during early development in response to maternal dietary modifications.

Allergenicity and cross-reactivity of coconut oil derivatives: A double-blind randomized controlled pilot study.

BACKGROUND: Counseling of patients with cocamidopropyl betaine (CAPB) allergy is difficult because the cross-reactivity of CAPB with other coconut-derived surfactants, coconut oil, and coconut fatty acids is largely unknown. OBJECTIVE: To provide pilot data regarding the cross-reactivity and allergenicity of surfactants derived from coconut oil. METHODS: A randomized double-blind controlled pilot study of 10 control patients and 12 patients previously found to be allergic to CAPB. Eleven coconut-derived surfactants, as well as coconut oil and lauric acid, were applied in random order according to standardized patch-test procedures with readings at 48 and 92 hours. The primary outcome measure was the frequency of positive patch-test reactions to each allergen. RESULTS: Only 3 of the 12 patients with previous reactions to CAPB reacted on retesting, and all of these reactions were doubtful. Fifty-nine percent of the study patients had reactions to triethanolamine polyethylene glycol-3 (TEA-PEG-3) cocamide sulfate as compared to none of the controls (p = .005). CONCLUSIONS: Reactions to CAPB were only 25% reproducible. These results substantiate previous experience that doubtful and mild reactions to CAPB may represent irritant reactions as opposed to true allergic reactions. TEA-PEG-3 cocamide sulfate was the only agent that had a statistically significant higher rate of reactions in the study group as compared to the control group.