Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy

BACKGROUND: Plasma concentrations of total homocysteine (tHcy) decrease during pregnancy. This reduction has been investigated in relation to folate status, but no study has addressed the possible role of betaine and its precursor choline. OBJECTIVE: We investigated the courses of plasma choline and betaine during normal human pregnancy and their relations to plasma tHcy. DESIGN: Blood samples were obtained monthly; the initial samples were taken at gestational week (GW) 9, and the last samples were taken approximately 3 mo postpartum. The study population comprised 50 women of West African descent. Most of the subjects took folic acid irregularly. RESULTS: Plasma choline (geometric x; 95% reference interval) increased continuously during pregnancy, from 6.6 (4.5, 9.7) micromol/L at GW 9 to 10.8 (7.4, 15.6) micromol/L at GW 36. Plasma betaine decreased in the first half of pregnancy, from 16.3 (8.6, 30.8) micromol/L at GW 9 to 10.3 (6.6, 16.2) micromol/L at GW 20 and remained constant thereafter. We confirmed a reduction in plasma tHcy, and the lowest concentration was found in the second trimester. From GW 16 onward, an inverse relation between plasma tHcy and betaine was observed. Multiple regression analysis showed that plasma betaine was a strong predictor of plasma tHcy from GW 20 onward. CONCLUSIONS: The steady increase in choline throughout gestation may ensure choline availability for placental transfer with subsequent use by the growing fetus. Betaine becomes a strong predictor of tHcy during the course of pregnancy. Both of these findings emphasize the importance of choline and betaine status during normal human pregnancy.     

Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study

BACKGROUND: Choline and betaine are found in a variety of plant and animal foods and were recently shown to be associated with decreased homocysteine concentrations. OBJECTIVE: The scope of this work was to investigate the associations between dietary choline and betaine consumption and various markers of low-grade systemic inflammation. DESIGN: Under the context of a cross-sectional survey that enrolled 1514 men (18-87 y of age) and 1528 women (18-89 y of age) with no history of cardiovascular disease (the ATTICA Study), fasting blood samples were collected and inflammatory markers were measured. Dietary habits were evaluated with a validated food-frequency questionnaire, and the intakes of choline and betaine were calculated from food-composition tables. RESULTS: Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-alpha (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-alpha (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants. CONCLUSIONS: Our results support an association between choline and betaine intakes and the inflammation process in free-eating and apparently healthy adults. However, further studies are needed to confirm or refute our findings.     

Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women

OBJECTIVE: To investigate the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD). DESIGN: Prospective cohort study. Subjects: A total of 16 165 women aged 49-70 years without prior CVD. Subjects were breast cancer screening participants in the PROSPECT-EPIC cohort, which is 1 of the 2 Dutch contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Each participant completed a validated food frequency questionnaire. Folate intake was calculated with the Dutch National Food Database. Betaine and choline intakes were calculated with the USDA database containing choline and betaine contents of common US foods. Data on coronary heart disease (CHD) events and cerebrovascular accident (CVA) events morbidity data were obtained from the Dutch Centre for Health Care Information. RESULTS: During a median follow-up period of 97 months, 717 women were diagnosed with CVD. After adjustment, neither folate, nor betaine, nor choline intakes were associated with CVD (hazard ratios for highest versus lowest quartile were 1.23 (95% confidence interval 0.75; 2.01), 0.90 (0.69; 1.17), 1.04 (0.71; 1.53), respectively). In a subsample of the population, high folate and choline intakes were statistically significantly associated with lower homocysteine levels. High betaine intake was associated with slightly lower high-density lipoprotein (HDL)-cholesterol concentrations. CONCLUSION: Regular dietary intakes of folate, betaine and choline were not associated with CVD risk in post-menopausal Dutch women. However, the effect of doses of betaine and choline beyond regular dietary intake--for example, via supplementation or fortification--remains unknown.     

Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans

Betaine, i.e., trimethylglycine, is linked to homocysteine metabolism. A 3-mo daily betaine supplementation decreased even normal plasma total homocysteine (tHcy) concentrations in humans. The pharmacokinetic characteristics and metabolism of betaine in humans have not been investigated in detail. The aim of this study was to assess the pharmacokinetics of orally administered betaine and its acute effect on plasma tHcy concentrations. Healthy volunteers (n = 10; 3 men, 7 women) with normal body weight (mean +/- SD, 69.5 +/- 17.0 kg), 40.8 +/- 12.4 y old, participated in the study. The betaine doses were 1, 3, and 6 g. The doses were mixed with 150 mL of orange juice and ingested after a 12-h overnight fast by each volunteer according to a randomized double-blind crossover design. Blood samples were drawn for 24 h and a 24-h urine collection was performed. Orally administered betaine had an immediate and dose-dependent effect on serum betaine concentration. Single doses of 3 and 6 g lowered plasma tHcy concentrations (P = 0.019 and P < 0.001, respectively), unlike the 1-g dose. After the highest dose, the concentrations remained low during the 24 h of monitoring. The change in plasma tHcy concentration was linearly associated with betaine dose (P = 0.006) and serum betaine concentration (R2 = 0.17, P = 0.025). The absorption and elimination of betaine were dose dependent. The urinary excretion of betaine seemed to increase with an increasing betaine dose, although a very small proportion of ingested betaine was excreted via urine. In conclusion, a single dose of orally administered betaine had an acute and dose-dependent effect on serum betaine concentration and resulted in lowered plasma tHcy concentrations within 2 h in healthy subjects.     

Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis

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 dimethylglycine. Previously, we have shown phospholipid malabsorption and increased plasma homocysteine in children with CF. In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15). Plasma choline, betaine, and dimethylglycine were significantly lower in children with CF (means +/- SEM, 6.48 +/- 0.35, 23.8 +/- 1.49, 1.49 +/- 0.13 mumol/L, respectively) than in children without CF (8.98 +/- 0.46, 37.3 +/- 1.84, 3.01 +/- 0.17 mumol/L, respectively). Plasma choline (r = 0.373, P = 0.007) and betaine (r = 0.399, P = 0.005) were positively related to methionine, and choline was inversely related to homocysteine (r = -0.316, P = 0.03). Choline, betaine, and dimethylglycine were all significantly and positively related to the plasma S-adenosylmethionine:S-adenosylhomocysteine (SAM:SAH) ratio (r = 0.294, r = 0.377, r = 0.442, respectively; P < 0.05). The plasma choline:betaine and betaine:dimethylglycine ratios did not differ between the children with CF and the control children, suggesting no increase in betaine synthesis, or betaine-dependent remethylation of homocysteine. These studies suggest that choline depletion may contribute to increased homocysteine in children with CF. Choline depletion and altered thiol metabolism may contribute to the clinical complications associated with CF.     

Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study

BACKGROUND: Epidemiologic studies of choline and betaine intakes have been sparse because a food-composition database was not available until recently. The physiologic relevance of a variation in dietary choline and betaine in the general population and the validity of intake assessed by food-frequency questionnaire (FFQ) have not been evaluated. OBJECTIVE: This study was conducted to examine the physiologic relevance and validity of choline and betaine intakes measured by an FFQ. DESIGN: We examined the relations between choline and betaine intakes measured by FFQ and plasma total homocysteine (tHcy) concentrations in 1960 participants from the Framingham Offspring Study. RESULTS: Higher intakes of dietary choline and betaine were related to lower tHcy concentrations independent of other determinants, including folate and other B vitamins. For the lowest and highest quintiles of dietary choline plus betaine, the multivariate geometric means for tHcy were 10.9 and 9.9 mumol/L (P for trend < 0.0001). The inverse association was manifested primarily in participants with low folate intakes (P for interaction < 0.0001). Among participants with folate intakes < or =250 microg/d, the geometric mean tHcy concentrations in the lowest and highest quintiles of choline plus betaine intakes were 12.4 and 10.2 micromol/L (P for trend < 0.0001). Except for choline from phosphatidylcholine, individual forms of choline were inversely associated with tHcy concentrations. CONCLUSIONS: Our findings provide support for a physiologically important variation in choline and betaine intakes in the general population and for the validity of intake measured by FFQ.     

血浆同型半胱氨酸与阿尔茨海默病关联性的Meta分析

目的通过Meta分析的方法对阿尔茨海默病（AD）与血浆同型半胱氨酸（Hcy）浓度的关联性及其影响因素进行评价。方法检索PubMed、CNKI等多个中英文数据库的相关文献,对检索到的文献进行质量评价后,摘录所需数据进行Meta分析和Meta回归分析。结果共纳入20篇合格文献,包括1 458例病例和1 402例对照。病例组同型半胱氨酸水平显著高于对照组,其合并标准化均数差（SMD）值及其95%置信区间为2.24（1.48,2.99）,而血浆叶酸和维生素B12浓度则不同程度的低于对照组。病例与对照之间血浆同型半胱氨酸浓度的差异受到叶酸、维生素B12等因素的影响,而与年龄等因素无关。结论血浆Hcy浓度的升高很可能是AD发病的危险因素,但其病因关联性以及叶酸维生素合剂的预防作用仍有待于在人群中开展大规模队列研究和随机对照实验研究加以论证。     

The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet

Background  

A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B₁₂ together with vitamin B₆ and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B₁₂ and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis.     

Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects

BACKGROUND: Betaine comes from the diet and from choline, and it is associated with vascular disease in some patient groups. Betaine supplementation lowers plasma total homocysteine. OBJECTIVE: We compared the acute effects of dietary and supplementary betaine and choline on plasma betaine and homocysteine under standard conditions and after a methionine load. DESIGN: In a randomized crossover study, 8 healthy men (19-40 y) consumed a betaine supplement (approximately 500 mg), high-betaine meal (approximately 517 mg), choline supplement (500 mg), high-choline meal (approximately 564 mg), high-betaine and -choline meal (approximately 517 mg betaine, approximately 622 mg choline), or a low-betaine and -choline control meal under standard conditions or postmethionine load. Plasma betaine, dimethylglycine, and homocysteine concentrations were measured hourly for 8 h and at 24 h after treatment. RESULTS: Dietary and supplementary betaine raised plasma betaine concentrations relative to control (P < 0.001) under standard conditions. This was not associated with raised plasma dimethylglycine concentration, and no significant betaine appeared in the urine. A small increase in dimethylglycine excretion was observed when either betaine or choline was supplied (P = 0.011 and < 0.001). Small decreases in plasma homocysteine 6 h after ingestion under standard conditions (P < or = 0.05) were detected after a high-betaine meal and after a high-betaine and high-choline meal. Dietary betaine and choline and betaine supplementation attenuated the increase in plasma homocysteine at both 4 and 6 h after a methionine load (P < or = 0.001). CONCLUSIONS: Dietary betaine and supplementary betaine acutely increase plasma betaine, and they and choline attenuate the postmethionine load rise in homocysteine concentrations.     

Calcium and magnesium dietary intakes and plasma and milk concentrations of Nepalese lactating women

Dietary calcium and magnesium intakes of 26 Nepalese lactating women were determined from analysis of 24-h duplicate food and beverage composites. In addition, blood, urine, and milk samples were collected. The mean Ca intake of these Nepalese mothers, 482 +/- 249 mg/d, was less than half that of American lactating women yet the Ca concentration of the milk was similar for the two groups of women. The Nepalese mothers appeared to maintain milk Ca concentrations by an increase in bone resorption as demonstrated by an elevated excretion of hydroxyproline. The Nepalese women had a mean Mg intake of 353 +/- 28 mg/d. Two locally available foods considered special for lactating women, jwano and gundruk, were examined for nutrient content and found to contain high concentrations of Ca and Mg. Increased consumption of these locally grown foods could add substantially to the Ca and Mg intakes of these lactating women.     

Selenium supplements do not increase plasma total homocysteine concentrations in men and women

Studies in rats indicate that plasma total homocysteine (tHcy) is decreased in selenium deficiency and increases with selenium supplementation. The aim of this study was to determine the effect of selenium supplements on plasma tHcy concentrations in a population that has suboptimal selenium status. Subjects from Dunedin, New Zealand (n = 189) were randomly assigned to receive a supplement containing 200 micro g selenium or placebo for 20 wk. At baseline, 67% (n = 112) of the participants had plasma selenium concentrations < 1.2 micro mol/L, a concentration believed to be that necessary for full glutathione peroxidase (Gpx) activity. At 20 wk, plasma selenium concentration and Gpx activity increased in the selenium group by 1.2 micro mol/L [95% confidence interval (CI): 1.1, 1.3] and 5.1 nkat/g protein (3.7, 6.5), respectively, changes that were significantly greater than the changes in the placebo group (P < 0.001). At 20 wk, mean changes in plasma tHcy concentrations were 0.1 micro mol/L (95% CI: -0.4, 0.5) and -0.2 micro mol/L (-0.7, 0.3) in the supplemented and placebo groups, respectively, compared to baseline. There was no difference in the mean changes in plasma tHcy between the supplemented and placebo groups (P = 0.54). These results suggest that selenium supplementation does not influence plasma tHcy concentrations in healthy populations in developed countries, whose selenium status is characterized by lower plasma selenium concentrations.     

The effect of low doses of betaine on plasma homocysteine in healthy volunteers

Homocysteine is a risk factor for vascular diseases, and lowering of plasma total homocysteine (tHcy) may be beneficial for health. Homocysteine can be remethylated to methionine by betaine-homocysteine methyltransferase using betaine (2(N,N,N-trimethyl)glycine) as methyl donor. A dose of 6 g betaine/d has been used in the treatment of homocystinuria, but data on the dose-response are scarce. Thirty-four healthy men and women were supplied with doses of 1, 3 and 6 g betaine and then with 6 g betaine+1 mg folic acid for four consecutive 1-week periods. The mean plasma tHcy concentration decreased by 1.1 (NS), 10.0 and 14.0 % (P<0.001) after supplementation with 1, 3 and 6 g betaine respectively. A further decrease in plasma tHcy by 5 % (P<0.01) was achieved by combining 1 mg folic acid with the 6 g betaine dose. Plasma betaine increased from 31 (sd 13) to 255 (sd 136) mumol/l in a dose-dependent manner (R(2) 0.97). We conclude that plasma tHcy is lowered rapidly and significantly by 3 or 6 g betaine/d in healthy men and women.     

Relationship of dimethylglycine, choline, and betaine with oxoproline in plasma of pregnant women and their newborn infants

Choline and glycine are inter-related through their roles in methyl metabolism. Choline is metabolized to betaine, which donates a methyl group to homocysteine to form methionine, also generating dimethylglycine, which is further metabolized to glycine. Choline is transported across the placenta and is higher in fetal than maternal plasma. Placental glycine transfer, however, is limited and poor glycine status has been suggested in preterm infants. Insufficient glycine for glutathione (GSH) synthesis results in increased metabolism of gamma-glutamyl cysteine to 5-oxoproline. We measured plasma 5-oxoproline as a metabolic indicator to address whether choline, via dimethylglycine, contributes physiologically relevant amounts of glycine in pregnancy. Blood was collected from healthy term pregnant women and their newborn infants at delivery (n = 46) and nonpregnant healthy women (n = 19) as a reference group. Plasma choline, betaine, dimethylglycine, homocysteine, methionine, and 5-oxoproline were quantified by HPLC-tandem MS. Plasma choline was 45% higher, but betaine was 63% lower and dimethylglycine was 28% lower in pregnant than nonpregnant women (P < 0.01). Higher white blood cell choline dehydrogenase messenger RNA levels in a random subset of pregnant (n = 8) than nonpregnant women (n = 7) (P < 0.01) suggest increased betaine and dimethylglycine turnover rather than decreased synthesis. Plasma choline, betaine, and dimethylglycine were higher (P < 0.001) in fetal plasma (36.4 +/- 13, 29.4 +/- 1.0, and 2.44 +/- 0.12 micromol/L, respectively) than maternal plasma (15.3 +/- 0.42, 14.1 +/- 0.6 and 1.81 +/- 0.12 micromol/L, respectively). Concentrations of 5-oxoproline and dimethylglycine were inversely (P < 0.05) correlated in maternal (Spearman rho = -0.35) and fetal plasma (Spearman rho = -0.32), suggesting that choline, via dimethylglycine, contributes glycine for GSH synthesis in human development.     

孕妇血浆同型半胱氨酸水平与早产的关系

目的:研究孕妇血浆同型半胱氨酸水平与早产的关系。方法:采用病例对照研究,用高效液相色谱荧光检测法(HPLC-FD)检测60例孕28~34周早产孕妇(病例组)和30例非早产于孕31~34周采血的正常妊娠孕妇(对照组)的血浆同型半胱氨酸水平。用Logistic回归分析等统计方法分析孕妇血浆同型半胱氨酸水平与早产的相关性。结果:病例组血浆同型半胱氨酸水平(7.56±2.97μmol/L)显著高于对照组(5.96±2.54μmol/L),P=0.013;排除混杂因素的影响,早产孕妇血浆同型半胱氨酸水平升高没有明显增加早产发生的风险,其血浆同型半胱氨酸水平升高会增加分娩早产小于胎龄儿(SGA)的机会,尤其是血浆同型半胱氨酸水平≥11.0μmol/L时分娩SGA的机会明显增加(χ2=8.579,P=0.003);未见早产儿其他并发症增加。结论:孕妇血浆同型半胱氨酸水平升高不会明显增加早产发生的风险,而会显著增加分娩小于胎龄儿的机会。     

Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women

High plasma homocysteine is a risk for cardiovascular disease and can be lowered through supplementation with 6 g/d of betaine. However, dietary intake of betaine is approximately 0.5-2 g/d. Therefore, we investigated whether betaine supplementation in the range of dietary intake lowers plasma homocysteine concentrations in healthy adults. Four groups of 19 healthy subjects ingested three doses of betaine or placebo daily for 6 wk. A methionine loading test was performed during run in, on d 1 of betaine supplementation, and after 2 and 6 wk of betaine supplementation. Fasting plasma homocysteine after 6-wk daily intakes of 1.5, 3 and 6 g of betaine was 12% (P < 0.01), 15% (P < 0.002) and 20% (P < 0.0001) less than in the placebo group, respectively. Furthermore, the increase in plasma homocysteine after methionine loading on the 1st d of betaine supplementation was 16% (P < 0.06), 23% (P < 0.008) and 35% (P < 0.0002) less than in the placebo group, respectively, and after 6 wk of supplementation was 23% (P < 0.02), 30% (P < 0.003) and 40% (P < 0.0002) less, respectively. Thus, doses of betaine in the range of dietary intake reduce fasting and postmethionine loading plasma homocysteine concentrations. A betaine-rich diet might therefore lower cardiovascular disease risk.     

Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women

Choline is involved in the synthesis of phospholipids, including blood lipids, and is the immediate precursor of betaine, which serves as a methyl group donor in a reaction converting homocysteine to methionine. Several cardiovascular risk factors are associated with plasma homocysteine, whereas little is known about their relationship to choline and betaine. We examined the relation of plasma choline and betaine to smoking, physical activity, BMI, percent body fat, waist circumference, blood pressure, serum lipids, and glucose in a population-based study of 7074 men and women aged 47-49 and 71-74 y. Overall plasma concentrations (means +/- SD) were 9.9 +/- 2.3 micromol/L for choline and 39.5 +/- 12.5 micromol/L for betaine. Choline and betaine were lower in women than in men and in younger subjects compared with older (P < 0.0001). Multivariate analyses showed that choline was positively associated with serum triglycerides, glucose, BMI, percent body fat, waist circumference (P < 0.0001 for all), and physical activity (P < 0.05) and inversely related to HDL cholesterol (P < 0.05) and smoking (P < 0.0001). Betaine was inversely associated with serum non-HDL cholesterol, triglycerides, BMI, percent body fat, waist circumference, systolic and diastolic blood pressure (P < 0.0001 for all), and smoking (P < 0.05) and positively associated with HDL cholesterol (P < 0.01) and physical activity (P < 0.0001). Thus, an unfavorable cardiovascular risk factor profile was associated with high choline and low betaine concentrations. Choline and betaine were associated in opposite directions with key components of metabolic syndrome, suggesting a disruption of mitochondrial choline dehydrogenase pathway.     

The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people

The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 microg cobalamin (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%, and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0.07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.     

Whole egg consumption increases plasma choline and betaine without affecting TMAO levels or gut microbiome in overweight postmenopausal women

As a crucial part of the symbiotic system, the gut microbiome is metabolically connected to many diseases and conditions, including cardiovascular diseases (CVD). Trimethylamine (TMA) is produced by gut bacteria from dietary choline, betaine, or L-carnitine, and is then converted in the liver to Trimethylamine N-oxide (TMAO), which in turn affects hepatic and intestinal lipid metabolism. Circulating TMAO is positively associated with CVD risk. Because eggs are rich in choline, it has been speculated that their consumption may increase plasma TMAO. In this study, we hypothesized that 2 eggs per day increases plasma TMAO level by altering gut microbiome composition in mildly hypercholesterolemic postmenopausal women. In this randomized, cross-over study, 20 overweight, postmenopausal women were given 2 whole eggs and the equivalent amount of yolk-free substitute as breakfast for 4 weeks, in randomized order, with a 4-week washout in between. Fasting blood draws and stool were collected at the beginning and end of each treatment period. Plasma TMAO, choline, betaine and other metabolites were analyzed using LC/MS, while gut microbiome composition was analyzed using 16S amplicon sequencing. Plasma choline and betaine were significantly increased after whole egg but not yolk-free substitute, however TMAO level was not significantly affected by treatments. Gut microbiome composition showed large inter-individual variability at baseline and in response to the treatments. The consumption of 2 eggs per day in overweight, postmenopausal mildly hypercholesterolemic women significantly increased plasma choline and betaine, but did not increase plasma TMAO or alter gut microbiome composition.     

Effect of protein and methionine intakes on plasma homocysteine concentrations: a 6-mo randomized controlled trial in overweight subjects

BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease. Homocysteine concentrations are thought to be raised by high protein and methionine intakes. OBJECTIVE: Our goal was to investigate the effects of high and low protein and methionine intakes on homocysteine in overweight subjects. DESIGN: Sixty-five overweight subjects were randomly assigned to a 6-mo intervention with a low-protein, low-methionine diet (LP: 12% of total energy, 1.4 g methionine/d; n = 25); a high-protein, high-methionine diet (HP: 22% of total energy, 2.7 g methionine/d; n = 25), both of which had similar fat contents (30% of total energy); or a control diet with an intermediate protein content (n = 15). All food was self-selected at a shop at the department. Protein intake was increased in the HP group mainly through lean meat and low-fat dairy products. Dietary compliance was evaluated by urinary nitrogen excretion. RESULTS: Homocysteine concentrations did not change significantly in the LP or control groups but were 25% lower in the HP group (NS). Homocysteine concentrations after the 3-mo intervention were inversely associated with vitamin B-12 intake and with weight change (by multivariate analysis performed for all subjects), but not with methionine or protein intake. Sixty-nine percent of the variation could be explained by baseline homocysteine (P < 0.001), 2% by vitamin B-12 (P = 0.02), and another 2% by weight change (P = 0.06). The plasma homocysteine concentration after 6 mo was associated only with baseline homocysteine (P < 0.001). CONCLUSION: A high-protein, high-methionine diet does not raise homocysteine concentrations compared with a low-protein, low-methionine diet in overweight subjects.