Betaine supplementation modulates betaine concentration by methylenetetrahydrofolate reductase genotype, but has no effect on amino acid profile in healthy active males: A randomized placebo-controlled cross-over study.

Betaine supplementation is used by athletes, but its mechanism of action is still not fully understood. We hypothesized that betaine supplementation would increase betaine concentration and alter amino acid profiles in relation to MTHFR genotype and dose in physically active males. The study followed a randomized placebo-controlled cross-over design. Blood samples were collected before and after each supplementation period. Serum was analyzed for amino acid profile, homocysteine, betaine, choline, and trimethylamine N-oxide (TMAO) concentrations. For the washout analysis, only participants starting with betaine were included (n = 20). Statistical analysis revealed no differences in the amino acid profile after betaine supplementation. However, betaine concentration significantly increased after betaine supplementation (from 4.89 ± 1.59 µg/mL to 17.31 ± 9.21 µg/mL, P < .001), with a greater increase observed in MTHFR (C677T, rs180113) T-allele carriers compared to CC (P = .027). Betaine supplementation caused a decrease in homocysteine concentration (from 17.04 ± 4.13 µmol/L to 15.44 ± 3.48 µmol/L, P = .00005) and a non-significant increase in TMAO concentrations (from 0.27 ± 0.20 µg/ml to 0.44 ± 0.70 µg/ml, P = .053), but had no effect on choline concentrations. Serum betaine concentrations were not significantly different after the 21-day washout from the baseline values (baseline: 4.93 ± 1.87 µg/mL and after washout: 4.70 ± 1.70 µg/mL, P = 1.000). In conclusion, betaine supplementation increased betaine and decreased homocysteine concentrations, but did not affect the amino acid profile or choline concentrations in healthy active males. Betaine concentrations may be dependent on MTHFR genotype.

Dietary choline intake in European and non-european populations: current status and future trends-a narrative review.

BACKGROUND: Choline is a nutrient necessary for the proper functioning of the body with a multidimensional impact on human health. However, comprehensive studies evaluating the dietary intake of choline are limited. The aim of this narrative review is to analyze current trends in choline intake in European and non-European populations. The secondary aim was to discuss possible future choline trends. METHODS: The search strategy involved a systematic approach to identifying relevant literature that met specific inclusion criteria. Observational studies and randomized clinical trials were searched for in PubMed and Scopus databases from January 2016 to April 2024. This review includes the characteristics of study groups, sample sizes, methods used to assess choline intake and time period, databases used to determine intake, choline intakes, and the main sources of choline in the diet. The review considered all population groups for which information on choline intake was collected. RESULTS: In most studies performed in Europe after 2015 choline intake did not exceed 80% of the AI standard value. The mean choline intake for adults in different European countries were 310 mg/day, while the highest value was reported for Polish men at 519 mg/day. In non-European countries, mean choline intakes were 293 mg/day and above. The main reported sources of choline in the diet are products of animal origin, mainly eggs and meat. The available data describing the potential intake of these products in the EU in the future predict an increase in egg intake by another 8% compared to 2008-2019 and a decrease in meat intake by about 2 kg per capita from 2018 to 2030. CONCLUSIONS: In the last decade, choline intake among adults has been insufficient, both in Europe and outside it. In each population group, including pregnant women, choline intake has been lower than recommended. Future choline intake may depend on trends in meat and egg consumption, but also on the rapidly growing market of plant-based products. However, the possible changes in the intake of the main sources of choline may lead to either no change or a slight increase in overall choline intake.

The effects of exposure to and timing of a choline-deficient diet during pregnancy and early postnatal life on the skeletal muscle transcriptome of the offspring.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is related to muscle loss, but the precise mechanism underlying this association remains unclear. The aim of the present study was thus to determine the influence of maternal fatty liver and dietary choline deficiency during pregnancy and/or lactation periods on the skeletal muscle gene expression profile among 24-day-old male rat offspring. METHODS: Histological examination of skeletal muscle tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global transcriptome pattern was assessed using a microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time PCR (qPCR). RESULTS: Morphological differences in fat accumulation in skeletal muscle related to choline supply were observed. The global gene expression profile was consistent with abnormal morphological changes. Mettl21c gene was overexpressed in all choline-deficient groups compared to the NN group, while two genes, Cdkn1a and S100a4, were downregulated. Processes of protein biosynthesis were upregulated, and processes related to cell proliferation and lipid metabolism were inhibited in DD, DN, and ND groups compared to the NN group. CONCLUSIONS: Prenatal and early postnatal exposure to fatty liver and dietary choline deficiency leads to changes in the transcriptome profile in skeletal muscle of 24-day old male rat offspring and is associated with muscle damage, but the mechanism of it seems to be different at different developmental stages of life. Adequate choline intake during pregnancy and lactation can prevent severe muscle disturbance in the progeny of females suffering from fatty liver.

The dose-dependent effect of caffeine supplementation on performance, reaction time and postural stability in CrossFit - a randomized placebo-controlled crossover trial.

BACKGROUND: Caffeine (CAF) ingestion improves performance in a broad range of exercise tasks. Nevertheless, the CAF-induced, dose-dependent effect on discipline-specific performance and cognitive functions in CrossFit/High-Intensity Functional Training (HIFT) has not been sufficiently investigated. The aim of this study was to evaluate the effect of acute supplementation of three different doses of CAF and placebo (PLA) on specific performance, reaction time (RTime), postural stability (PStab), heart rate (HR) and perceived exertion (RPE). METHODS: In a randomized double-blind placebo-controlled crossover design, acute pre-exercise supplementation with CAF (3, 6, or 9 mg/kg body mass (BM)) and PLA in 26 moderately trained CrossFit practitioners was examined. The study protocol involved five separate testing sessions using the Fight Gone Bad test (FGB) as the exercise performance evaluation and biochemical analyses, HR and RPE monitoring, as well as the assessment of RTime and PStab, with regard to CYP1A2 (rs762551) and ADORA2A (rs5751876) single nucleotide polymorphism (SNP). RESULTS: Supplementation of 6 mgCAF/kgBM induced clinically noticeable improvements in FGBTotal results, RTime and pre-exercise motor time. Nevertheless, there were no significant differences between any CAF doses and PLA in FGBTotal, HRmax, HRmean, RPE, pre/post-exercise RTime, PStab variables or pyruvate concentrations. Lactate concentration was higher (p < 0.05) before and after exercise in all CAF doses than in PLA. There was no effect of CYP1A2 or ADORA2A SNPs on performance. CONCLUSIONS: The dose-dependent effect of CAF supplementation appears to be limited to statistically nonsignificant but clinically considered changes on specific performance, RTime, PStab, RPE or HR. However, regarding practical CAF-induced performance implications in CrossFit/HIFT, 6 mgCAF/kgBM may be supposed as the most rational supplementation strategy.

Genetic risk score for gestational weight gain.

Gestational weight gain (GWG) involves health consequences for both mother and offspring. Genetic factors seem to play a role in the GWG trait. For small effect sizes of a single genetic polymorphism (SNP), a genetic risk score (GRS) summarizing risk-associated variation from multiple SNPs can serve as an effective approach to genetic association analysis. The aim of the study was to analyze the association between genetic risk score (GRS) and gestational weight gain (GWG). GWG was calculated for a total of 342 healthy Polish women of Caucasian origin, aged 19 to 45 years. The SNPs rs9939609 (FTO), rs6548238 (TMEM18), rs17782313 (MC4R), rs10938397 (GNPDA2), rs10913469 (SEC16B), rs1137101 (LEPR), rs7799039 (LEP), and rs5443 (GNB3) were genotyped using commercial TaqMan SNP assays. A simple genetic risk score was calculated into two ways: GRS1 based on the sum of risk alleles from each of the SNPs, while GRS2 based on the sum of risk alleles of FTO, LEPR, LEP, and GNB3. Positive association between GRS2 and GWG (ß = 0.12, p = 0.029) was observed. Genetic risk variants of TMEM18 (p = 0.006, OR = 2.6) and GNB3 (p < 0.001, OR = 3.3) are more frequent in women with increased GWG, but a risk variant of GNPDA2 (p < 0.001, OR = 2.7) is more frequent in women with adequate GWG, and a risk variant of LEPR (p = 0.011, OR = 3.1) in women with decreased GWG. GRS2 and genetic variants of TMEM18, GNB3, GNPDA2, and LEPR are associated with weight gain during pregnancy.

Maternal cafeteria diet influences kisspeptin (Kiss1), kisspeptin receptor(Gpr54), and sirtuin (Sirt1) genes, hormonal and metabolic profiles, and reproductive functions in rat offspring in a sex-specific manner†.

Kisspeptin (KP, encoded by Kiss1, binding to the Gpr54 receptor) is a neuropeptide conveying information on the metabolic status to the hypothalamic-pituitary-gonadal axis. KP acts together with dynorphin A (encoded by Pdyn) and neurokinin B (encoded by Tac2) to regulate reproduction. KP is crucial for the onset of puberty and is under the control of sirtuin (encoded by Sirt1). We hypothesize that the maternal cafeteria (CAF) diet has adverse effects on the offspring's hormonal, metabolic, and reproductive functions due to sex-specific alterations in the expression of Kiss1, Gpr54, Pdyn, Tac2, and Sirt1 in the hypothalamus, and Kiss1, Gpr54, and Sirt1 in the liver. Rats were fed a CAF diet before pregnancy, during pregnancy, and during lactation. The vaginal opening was monitored. Offspring were sacrificed in three age points: PND 30, PND 35, and PND 60 (females) and PND 40, PND 45, and PND 60 (males). Their metabolic and hormonal status was assessed. mRNA for Kiss1, Gpr54, Pdyn, Tac2, and Sirt1 were measured by real-time PCR in the hypothalamus and/or livers. We found that CAF offspring had lower weight and altered body composition; increased cholesterol and triglyceride levels, sex-specific changes in glucose and insulin levels; sex-dependent changes in Sirt1/Kiss1 mRNA ratio in the hypothalamus; sex-specific alterations in Kiss1 and Sirt1 mRNA in the liver with more diversity in males; and a delayed puberty onset in females. We concluded that the mother's CAF diet leads to sex-specific alterations in metabolic and reproductive outcomes via Kiss1/Gpr54 and Sirt1 systems in offspring.

Betaine supplementation improves CrossFit performance and increases testosterone levels, but has no influence on Wingate power: randomized crossover trial.

BACKGROUND: Because betaine (BET) supplementation may improve muscular strength and endurance, it seems plausible that BET will also influence CrossFit performance (CF). PURPOSE: The aim of this study was to evaluate the effects of three weeks of BET supplementation on body composition, CF performance, muscle power in the Wingate anaerobic test (WAnT), and the concentrations of selected hormones. The secondary aims were to analyze the effectiveness of two different BET doses (2.5 and 5.0 g/d) and their interaction with the methylenetetrahydrofolate reductase (MTHFR) genotype. METHODS: The study was designed in a double-blinded randomized cross-over fashion. Forty-three CF practitioners completed the entire study. CF performance was measured using the Fight Gone Bad (FGB) workout and muscle power was evaluated in a 30-second WAnT. Body composition was determined by air-displacement plethysmography. Blood was drawn to assess hormone concentrations. The C677T single nucleotide polymorphism (rs180113) in the MTHFR gene was analyzed. RESULTS: FGB total improved with BET by 8.7 ± 13.6% (p < 0.001), but no significant changes were observed with placebo (- 0.4 ± 10.0%, p = 0.128). No changes were also observed in WAnT and body composition. After BET supplementation testosterone concentration increased by 7.0 ± 15.4% with BET (p = 0.046) (no change with placebo: 1.5 ± 19.6%, p = 0.884) but had no effect on concentrations of insulin-like growth factor or cortisol. Finally, there were no significant interactions between MTHFR genotype and BET dose in any outcome. CONCLUSIONS: BET supplementation may improve CF performance and increase testosterone concentration. However, there was no evidence of a difference between dosages (2.5 and 5.0 g/d) and MTHFR genotypes. The trial was registered on clinicaltrials.gov (NCT03702205) on 10 October 2018.

Caffeine Consumption in Polish Adults: Development and Validation of a Polish Questionnaire for Assessing Caffeine Intake.

Objective: Caffeine is one of the oldest natural substances consumed by people. Its consumption in Poland has not been well described. The aim of this study was to design and validate an online food frequency questionnaire (FFQ) on caffeine intake and to use it to estimate caffeine consumption in Polish adults.Method: The FFQ was prepared and validated in a pilot study. The intake assessment was conducted in 2019-2020 on 372 respondents, aged 18 to 60 years. The FFQ included products such as coffee, tea, energy drinks, and carbonated drinks, as well as supplements and chocolate.Results: We showed good repeatability of the FFQ and it was considered a valid tool. The mean total caffeine intake among all participants was 426.7 mg ± 283.4 mg/day of all sources; in women, it was 446.4 mg ± 306.2 mg/day, while in men, it was 394.1 ± 236.4 mg/day. Forty-three percent of the respondents consumed more than 400 mg of caffeine/day. Coffee was the main source of caffeine and contributed to 65% of total caffeine consumption. Women consumed 90% more green tea than men (p < 0.01). Overweight and obese people have 20% greater total caffeine intake (p = 0.01) and consumed 20% more coffee (p = 0.02) and 30% more black tea (p = 0.01) than people of normal weight.Conclusions: Average caffeine consumption among Polish adults slightly exceeds the safe consumption dose established by the European Food Safety Authority. Body weight status can differentiate caffeine intake.

The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1α Gene Expression.

The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate concentrations, and exercise-associated biomarkers. Eighteen recreationally trained males (25 ± 5 y) were randomized to supplement 6 g/day of either betaine anhydrous (BET) or cellulose placebo (PLA) for 14 days. Subsequently, subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs (BFR [LL-BFR; 20% 1RM at 80% arterial occlusion pressure] and high-load [HL; 70% 1RM]). Toe-tip lactate concentrations were sampled before (PRE), as well as immediately (POST0), 30 min (POST30M), and 3 h (POST3H) post-exercise. Serum homocysteine (HCY), growth hormone (GH) and insulin-like growth factor-1 concentrations were additionally assessed at PRE and POST30M. Analysis failed to detect any significant between-supplement differences for total repetitions completed. Baseline lactate changes (∆) were significantly elevated from POST0 to POST30 and from POST30 to POST3H (p < 0.05), whereby HL additionally demonstrated significantly higher ∆Lactate versus LL-BFR (p < 0.001) at POST3H. Although serum ∆GH was not significantly impacted by supplement or condition, serum ∆IGF-1 was significantly (p = 0.042) higher in BET versus PLA and serum ∆HCY was greater in HL relative to LL-BFR (p = 0.044). Although these data fail to support a BFR-betaine synergy, they otherwise support betaine's anabolic potential.

The Effect of 3-Week Betaine Supplementation on Blood Biomarkers of Cardiometabolic Health in Young Physically Active Males.

Betaine (BET) supplementation decreases homocysteine concentration in plasma, but it may also have an adverse effect on health by increasing blood lipid concentrations, at least in overweight and obese individuals. The aim of this study was to evaluate the effect of BET supplementation on the lipid profile and concentrations of homocysteine, inflammatory cytokines, and liver enzymes in physically active, healthy males. This was a randomized, placebo (PL)-controlled, double-blinded, crossover trial. BET (2.5 or 5.0 g/d) was administered for 21 days. Before and after supplementation with BET or PL, anthropometric measurements and blood were collected in a fasted state. Our results show that BET supplementation significantly decreased homocysteine concentration (from 17.1 ± 4.0 µmol/L before BET to 15.6 ± 3.5 µmol/L after BET, p = 0.009, η2 = 0.164). However, the intervention had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerol, interleukins 1ß and 6, and tumour necrosis factor α concentrations, or alanine and aspartate activities. In addition, there were no interactions between the MTHFR genotype and BET dose. In conclusion, BET supplementation may be beneficial for homocysteine concentration in healthy, physically active males, with no detrimental effect on lipid profile.

Functional single-nucleotide polymorphism (rs762551) in CYP1A2 gene affects white coffee intake in healthy 20- to 40-year-old adults.

Coffee is one of the most consumed beverages in the world, but the extent to which it is consumed is affected by both environmental and genetic factors. Genome-wide association studies and candidate date association studies have identified several gene variants associated with increased consumption of coffee. Functional single-nucleotide polymorphisms in rs762551 (cytochrome P450 1A2 [CYP1A2]) and rs5751876 (adenosine receptor A2A [ADORA2A]) has been linked to individual caffeine response. Coffee intake has been shown to affect lipid metabolism. We thus hypothesize that rs762551 (CYP1A2) A allele carriers consume more coffee than C allele carriers and that rs5751876 (ADORA2A) C allele carriers consume less coffee than T allele carriers. Additionally, we hypothesize that CYP1A2 genotype can modulate serum glucose concentrations and lipid profile. A total of 421 participants aged 20 to 40 years were recruited from 2016 to 2018 in Poznan, Poland. Genotyping of CYP1A2 and ADORA2A was performed using TaqMan probes. Individuals with AA CYP1A2 genotype consumed relatively more coffee with milk (72.81 ± 10.15 mL/1000 kcal vs 43.38 ± 6.42 mL/1000 kcal, P = .008) and with milk or cream than did C allele carriers, whereas the rs5751876 ADORA2A polymorphism was not associated with coffee or tea intake. Additionally, subjects with AA CYP1A2 genotype had 10% higher serum triacylglycerol (TG) concentrations than C allele carriers. This study suggests that CYP1A2 rs762551 polymorphism is associated with coffee intake and serum TG concentrations in healthy 20- to 40-year-old adults.

Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex-dependent.

BACKGROUND: Choline and its metabolites apppear to have relationships with body mass index (BMI), body fat, and body weight, but the research results have proved inconsistent. We thus investigated the associations of plasma levels of trimethylamine N-oxide (TMAO), choline, and betaine with anthropometric measurements, including modulatory effects of genetics and diet. METHODS: The study was performed on a group of 421 adults, aged 20-40 years, who had been recruited in Poland. Plasma concentrations of choline, betaine, and TMAO were determined using reverse-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry. The following polymorphisms were genotyped using TaqMan probes: rs180113 (MTHFR), rs70991108 (DHFR), rs2236225 (MTHFD1), and rs7946 and rs12325817 (PEMT). We employed multivariate linear regression to examine the associations between anthropometric measurements, one-carbon metabolism metabolites, and genotypes. RESULTS: Higher plasma choline was associated with higher BMI (ß = 0.17; p < 0.01), body weight (ß = 0.11; p < 0.05), body fat mass (FM) (ß = 0.10; p < 0.05), and waist circumference (WC) (ß = 0.14; p < 0.01), whereas higher choline intake was associated with lower body FM (ß = -0.14; p < 0.01) and lower WC (ß = -0.12; p < 0.01). After stratification by sex, plasma betaine was found to be associated with lower BMI (ß = -0.20; p < 0.05) and body weight (ß = -0.16; p < 0.05) in men only, whereas choline intake was associated with lower body FM (ß = -0.19; p < 0.05) and waist-to-hip ratio (WHR) (ß = -0.19; p < 0.05) and MTHFR CC genotype was associated with WHR (ß = 0.15; p < 0.05) in women only. CONCLUSIONS: Higher plasma betaine and higher dietary choline are associated with lower FM and body weight, whereas higher plasma choline is positively associated with body weight status and adiposity. Moreover, these associations appear to be sex-specific.

Ex vivo folate production by fecal bacteria does not predict human blood folate status: Associations between dietary patterns, gut microbiota, and folate metabolism.

Although some bacteria inhabiting the human gut synthesize folates, it has not yet been established whether bacterial folate biosynthesis can impact human folate status. The main objectives of this study were to evaluate associations between different lifestyle factors and the potential of fecal microbiota to produce folates, and to investigate whether this potential is associated with circulating folate and total homocysteine (tHcy) levels in humans. To this end, we carried out an observational study of two hundred adult participants, with high variance in dietary habits. Diet was determined using three-day food records. Fecal microbiota composition was assessed by 16S rRNA gene amplicon sequencing. To establish the folate-production potential of fecal bacteria, cultures containing feces were incubated under anaerobic conditions for 24 h, and the folate concentration was measured before and after incubation. The folate concentration in cultures was 185.4 ± 228.1 pg/ml/log(CFU/g) (2125.4 ± 2454.3 pg/ml) higher after incubation. This change in concentration was not associated with the healthy eating index that measures diet quality (r = -0.11, p = 0.11), but it was positively associated with low α-diversity (r = -0.18, p < 0.01), and high relative abundance of the Bacteroides, as well as Sutterella and Parasutterella genera. The gut microbiota's folate producing potential was associated neither with serum folate nor with plasma tHcy levels. In conclusion, some taxa of the native gut microbiota have the ability to synthesize folates under culture conditions, but this bacterial folate biosynthesis capacity does not predict human folate status.

Human gut microbiota composition and its predicted functional properties in people with western and healthy dietary patterns.

PURPOSE: Some dietary habits cluster together, and for this reason it is advised to study the impact of entire dietary patterns on human health, rather than that of individual dietary habits. The main objective of this study was to evaluate differences in gut microbiota composition and their predicted functional properties between people with a healthy (HDP) and western (WDP) dietary pattern. METHODS: A cross-sectional, observational study was carried out on 200 participants enrolled 2017-2018 in Poznan, Poland, equally distributed into HDP and WDP groups. Diet was estimated using 3-day food records and information on stool transit times was collected. Fecal microbiota composition was assessed by 16S rRNA gene sequencing and its functional properties were predicted by the PICRUSt2 workflow. RESULTS: The α-diversity did not differ between people with WDP and HDP, but ß-diversity was associated with dietary pattern. People with HDP had higher relative abundances (RA) of Firmicutes and Faecalibacterium and lower RA of Bacteroidota and Escherichia-Shigella than participants with WDP. Only a small proportion of the variance in microbiota composition (1.8%) and its functional properties (2.9%) could be explained by dietary intake (legumes, simple sugars and their sources, like fruit, soft drinks) and stool transit characteristics. CONCLUSION: Gut microbiota composition and predicted metabolic potential is shaped by overall diet quality as well as the frequency of defecation; however, the cumulative effect of these explain only a relatively low proportion of variance.

Diet, Trimethylamine Metabolism, and Mitochondrial DNA: An Observational Study.

SCOPE: Mitochondrial DNA copy number (mtDNAcn) and its methylation level in the D-loop area have been correlated with metabolic health and are suggested to vary in response to environmental stimuli, including diet. Circulating levels of trimethylamine-n-oxide (TMAO), which is an oxidative derivative of the trimethylamine (TMA) produced by the gut microbiome from dietary precursors, have been associated with chronic diseases and are suggested to have an impact on mitochondrial dynamics. This study is aimed to investigate the relationship between diet, TMA, TMAO, and mtDNAcn, as well as DNA methylation. METHODS AND RESULTS: Two hundred subjects with extreme (healthy and unhealthy) dietary patterns are recruited. Dietary records are collected to assess their nutrient intake and diets' quality (Healthy Eating Index). Blood levels of TMA and TMAO, circulating levels of TMA precursors and their dietary intakes are measured. MtDNAcn, nuclear DNA methylation long interspersed nuclear element 1 (LINE-1), and strand-specific D-loop methylation levels are assessed. There is no association between dietary patterns and mtDNAcn. The TMAO/TMA ratio is negatively correlated with d-loop methylation levels but positively with mtDNAcn. CONCLUSIONS: These findings suggest a potential association between TMA metabolism and mitochondrial dynamics (and mtDNA), indicating a new avenue for further research.

Lower plasma glutathione, choline, and betaine concentrations are associated with fatty liver in postmenopausal women.

Postmenopausal women are at high risk of hepatic steatosis, which may be associated one-carbon metabolism (OCM) abnormalities. We hypothesized that lower folate, choline, betaine, and glutathione (GSH) concentrations but higher total homocysteine and trimethylamine N-oxide concentrations are associated with fatty liver (FL) in postmenopausal women. We aimed to identify relationships between OCM and nonalcoholic fatty liver disease biomarkers in postmenopausal women. A total of 131 postmenopausal women participated in this study and were stratified by the incidence of FL based on the hepatic steatosis index (HSI). Food intake was evaluated using dietary records. Aspartate aminotransferase and alanine aminotransferase concentrations in serum were measured using the colorimetric method. Total homocysteine and GSH concentrations in plasma were measured using high-performance liquid chromatography. Folate and phosphatidylcholine (PC) concentrations were determined in red blood cells using an enzyme-linked immunosorbent assay. Other OCM biomarkers concentrations were measured using the isotope dilution analysis. Women with FL (HSI > 36) had lower GSH, choline, and betaine concentrations than women without FL (HSI < 36). Higher HSI level was negatively correlated with betaine and PC and positively correlated with plasma choline/betaine ratio. Lower GSH and higher carnitine concentrations in the blood are associated with an increased risk of FL. MTHFR (rs180130) T-allele carriers had lower levels of GSH than the CC homozygotes. Postmenopausal women with FL have lower GSH, choline, and betaine concentrations, which may play a role in fat accumulation in the liver. It seems important to consider the dietary intakes of these nutrients in postmenopausal women.

ß-glucuronidase activity is associated with carbohydrate metabolism but not with androgen status in overweight and obese women with polycystic ovary syndrome.

OBJECTIVES: The aim of this study was to evaluate the relationship between ß-glucuronidase and androgen levels in overweight and obese women with polycystic ovary syndrome (PCOS). The connection between ß-glucuronidase, the abundance of selected gut bacteria, carbohydrate metabolism, and diet quality was also determined. METHODS: This cross-sectional study was conducted with 56 women with a mean age of 29.14 ± 5.11 y and a mean body mass index (BMI) of 34.15 ± 5.72 kg/m2. Anthropometrical parameters, fecal ß-glucosidase activity, and selected food frequency intake were measured. RESULTS: Women with better quality diets, apart from lower BMI and better carbohydrate metabolism parameters, had more abundant Faecalibacterium prausnitzii and Akkermansia muciniphila. Two-hour oral glucose tolerance test (OGTT-2h-glu; mg/dL) was the main predictor of ß-glucuronidase activity and there was no relationship between ß-glucuronidase activity and androgen levels. Non-Healthy Diet Index-14 (nHDI-14) was the main predictor for A. muciniphila, Bifidobacteriu. longum, and F. prausnitzii abundance. QUICKI was a significant predictor of A. muciniphila abundance and OGTT-2h-glu was a significant predictor of F. prausnitzii abundance. CONCLUSION: There was no relationship between ß-glucuronidase activity and androgen levels in overweight and obese women with PCOS, but ß-glucuronidase activity may be an important factor in carbohydrate metabolism. Modulation of the abundances of F. prausnitzii, A. muciniphila, and B. longum using special diets should thus be considered a promising intervention.

Human Serum Betaine and Associated Biomarker Concentrations Following a 14 Day Supplemental Betaine Loading Protocol and during a 28 Day Washout Period: A Pilot Investigation.

Several previous investigations have employed betaine supplementation in randomized controlled crossover designs to assess its ostensible ergogenic potential. Nevertheless, prior methodology is predicated on limited pharmacokinetic data and an appropriate betaine-specific washout period is hitherto undescribed. The purpose of the present pilot investigation was therein to determine whether a 28 day washout period was sufficient to return serum betaine concentrations to baseline following a supplementation protocol. Five resistance-trained men (26 ± 6 y) supplemented with 6 g/day betaine anhydrous for 14 days and subsequently visited the lab 10 additional times during a 28 day washout period. Participants underwent venipuncture to assess serum betaine and several other parameters before (PRE) and periodically throughout the washout timeframe (POST0, -4, -7, -10, -13, -16, -19, -22, -25 and -28). All analyses were performed at a significance level of p < 0.05. While analyses failed to detect any differences in any other serum biomarker (p > 0.05), serum betaine was significantly elevated from PRE-to-POST0 (p = 0.047; 2.31 ± 1.05 to 11.1 ± 4.91 µg·mL−1) and was statistically indistinguishable from baseline at POST4 (p = 1.00). Nevertheless, visual data assessment and an inability to assess skeletal muscle concentrations would otherwise suggest that a more conservative 7 day washout period is sufficient to truly return both serum-and-skeletal muscle betaine content to pre-supplementation levels.