Explore the vast range of titles available.

An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B(12) (0.5 mg/d) and vitamin B(6) (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P =  0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P =  0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Controlled-Trials.com ISRCTN94410159.

Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

INTRODUCTION Elevated total homocysteine (tHcy) is a major predictor of brain atrophy, cognitive decline, and Alzheimer's disease (AD) progression. The VITACOG trial, a randomized, placebo‐controlled study in mild cognitive impairment (MCI), previously showed that B vitamin supplementation lowered tHcy, slowing brain atrophy and cognitive decline; however, the underlying mechanisms remained unclear. METHODS We used untargeted, multi‐platform metabolomics, with nuclear magnetic resonance and liquid chromatography‐mass spectrometry to analyze serum samples from 89 B vitamin–treated and 84 placebo‐treated MCI participants over a 2 year follow‐up period. RESULTS Multivariate modeling distinguished treated from placebo groups with 91.2 ± 1.8% accuracy. B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, α‐ketoglutarate, α‐ketobutyrate, glucose, and glutamate. DISCUSSION These findings reveal that B vitamins influence metabolic pathways beyond tHcy reduction, particularly the tricarboxylic acid cycle and glutamine–glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression. Highlights Nuclear magnetic resonance and multi‐platform liquid chromatography tandem mass spectrometry metabolomics were performed on serum samples from 89 B vitamin–treated and 84 placebo participants in the VITACOG trial. Multi‐platform metabolomics revealed B vitamin–driven metabolic reprogramming, achieving 91% classification accuracy. B vitamin supplementation modulates key neuroprotective metabolic pathways. Regulation of energy metabolism and neurotransmission by B vitamins contributes to brain health in elderly individuals. B vitamins demonstrate potential as an adjunct therapy in mild cognitive impairment, potentially mitigating progression to Alzheimer's disease.

Background While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. Methods This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. Results The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. Conclusions This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. ClinicalTrials.gov Identifier NCT03472508 (Registration Date: March 21, 2018).

Metabolic syndrome (MetS) in postmenopausal women is an important risk factor for cardiovascular morbidity, especially stroke and coronary heart disease and mortality. Preventing and treating MetS would be useful in preventing disability and promoting normal aging. Previous human studies have found some beneficial effects of Lactobacillus species on some isolated parameters of MetS. Nevertheless, we are not aware, to date, of any study which has verified the influence of probiotics in patients with MetS. Therefore, the aim of the present study was to evaluate the influence of fermented milk with L. plantarum in the classical parameters related to MetS, as well as in other parameters related to cardiovascular risk in postmenopausal women. Twenty-four individuals were paired by age, ethnicity, and body mass index in two groups: Non-fermented milk (NFM = 12) 80 mL/d and fermented milk (FM = 12) 80 mL/d. Anthropometric and blood pressure measurements, biochemical, inflammatory, and immunologic biomarkers were measured. Total cholesterol and γ-glutamyltranspeptidase had a significant reduction both in NFM (P = 0.043 and P = 0.036, respectively) and FM groups (P = 0.010 and P = 0.018, respectively) after 90 d, whereas low-density lipoprotein cholesterol showed a significant reduction in NFM group (P = 0.002) and trend in the FM group (P = 0.092). Glucose and homocysteine levels showed a significant reduction in the FM group compared with the NFM group (P = 0.037 and P = 0.019, respectively). In relation to inflammatory biomarkers, there was a significant decrease in interleukin-6 both in NFM (P = 0.032) and in FM (P = 0.001) groups. FM with L. plantarum showed more favorable results than NFM in relation to cardiovascular risk factors in postmenopausal women with MetS.

Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5′-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40–75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: −39.7% to −20.3%) and LDL-C by 7.5% (95% CI: −10.3% to −4.7%), compared to the placebo (p < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: −62.3% to −34.3%, p < 0.01) compared to mixed allele carriers (18.6%, 95% CI: −25.6% to −11.6%, p < 0.01), with a notable intergroup difference (29.7%, 95% CI: −50.7% to −8.7%, p < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: −15.8% to −7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: −6.8% to −2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: −13.0% to −1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.

Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50–70 years with raised plasma total homocysteine and normal serum vitamin B 12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 μg daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0·132, 95% CI 0·032 to 0·233), information processing speed (0·087, 0·016 to 0·158) and sensorimotor speed (0·064, −0·001 to 0·129) were significantly better in the folic acid group than in the placebo group. Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

PURPOSE: Poor vitamin B12 (B12) status is associated with adverse outcomes in pregnancy and infancy. Little is known about effects of B12 supplementation on immune function. The present study aimed to evaluate effects of pre- and postnatal B12 supplementation on biomarkers of B12 status and vaccine-specific responses in mothers and infants. METHOD: In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, age 18–35 years, hemoglobin <110 g/L, 11–14 weeks pregnant) were randomized to receive 250 μg/day B12 or a placebo throughout pregnancy and 3-month postpartum along with 60 mg iron + 400 μg folate. Women were immunized with pandemic influenza A (H1N1) vaccine at 26- to 28-week gestation. Blood from mothers (baseline, 72-h post-delivery, 3-month postpartum), newborns and infants (3-month) was analyzed for hemoglobin, B12, methylmalonic acid (MMA), total homocysteine (tHcy), ferritin and serum transferrin receptor, C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP). Vitamin B12 was also assessed in breast milk. H1N1-specific antibodies were determined in plasma and colostrum/breast milk. RESULTS: At baseline, 26 % women were B12 deficient (<150 pmol/L), 40 % had marginal status (150–220 pmol/L), 43 % had elevated MMA (>271 nmol/L), and 31 % had elevated tHcy (>10 μmol/L). Supplementation increased B12 in plasma, colostrums and breast milk (p < 0.05) and lowered MMA in neonates, mothers and infants at 3 months (p < 0.05). B12 supplementation significantly increased H1N1-specific IgA responses in plasma and colostrums in mothers and reduced proportion of infants with elevated AGP and CRP compared with placebo. CONCLUSION: Supplementation with 250 μg/day B12 during pregnancy and lactation substantially improved maternal, infant and breast milk B12 status. Maternal supplementation improved H1N1 vaccine-specific responses in mothers only and may alleviate inflammatory responses in infants.

Elevated total homocysteine level (tHcy) has been hypothesized to be associated with morbidity and mortality of stroke; however, results regarding the association between plasma tHcy status and prognosis of acute ischemic stroke are inconsistent. Moreover, the gender effect on this association has yet to be explored. We thus prospectively investigated whether higher tHcy concentrations predicted poor stroke prognosis in Chinese adults. A total of 3309 acute ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Baseline tHcy concentrations were quantitatively determined via enzymatic cycling assay. The primary outcome was a combination of death and major disability at 3 months (modified Rankin scale scores 3–6) after hospitalization. Multivariate logistic regression models with restricted cubic splines were used to determine the association between baseline plasma tHcy and the subsequent outcome. Higher plasma tHcy concentrations were associated with increased risks of the primary outcome in women but not in men ( P interaction  = 0.016). Adjusted odds ratios comparing two extreme tHcy quartiles were 1.83 (95 % confidence interval 1.12–2.98; P trend  = 0.02) in women and 0.87 (95 % confidence interval 0.61–1.25; P trend  = 0.37) in men. The significant association between baseline tHcy status and stroke prognosis in women, but not in men, persisted in further subgroup analyses, stratified by age, baseline systolic blood pressure, and other pre-specified factors. Elevated tHcy is positively associated with poor prognosis of acute ischemic stroke in women, but not in men. Further studies are needed to replicate our findings and to clarify the potential sex-specific mechanisms.

Background A1298C polymorphism of the MTHFR gene and blood homocysteine levels are reported to be associated with the development of proteinuria in patients with type 2 diabetes mellitus; however, data remain limited. Objectives To determine the characteristics of A1298C polymorphism and blood homocysteine levels as well as their association with proteinuria in patients with type 2 diabetes mellitus. Materials and methods A cross-sectional study with convenient sampling was performed among patients with type 2 diabetes mellitus who visited the Can Tho University of Medicine and Pharmacy Hospital between August 2023 and August 2024. Blood samples were collected for genetic sequencing and homocysteine level testing. Proteinuria was defined as an albumin-to-creatinine ratio ≥30 mg/g. Results In total, 192 patients with a mean age of 63.9 ± 13.1 years were enrolled. Males accounted for 34.9% of the study population. Analysis of A1298C polymorphism revealed genotype distributions of AA, AC, and CC genotypes as 51.6%, 41.1%, and 7.3%, respectively. A significant association was observed between A1298C polymorphism and elevated homocysteine levels, with CC genotype exhibiting a higher prevalence of hyperhomocysteinemia (28.6%) than AA (6.1%) and AC (22.8%) genotypes. Patients carrying AC+CC genotypes had a 2.40-fold higher risk of developing proteinuria (95% confidence interval: 1.30–4.41, p < 0.05) than those with AA genotype. Elevated blood homocysteine levels were associated with an 8.98-fold increased risk of proteinuria (95% confidence interval: 2.06–39.11, p < 0.05). Independent factors associated with proteinuria included age (odds ratio = 0.97), elevated homocysteine levels (odds ratio = 8.79), and AC+CC genotype (odds ratio = 2.08). Conclusion A1298C polymorphism was characterized by allele frequencies of 72.1% for A and 27.9% for C. In addition to age, the presence of the C allele and elevated blood homocysteine levels were identified as independent risk factors for proteinuria in patients with type 2 diabetes mellitus.