B-Complex

Background and Purpose: The effects of B-vitamin combinations on the prevention of cardiovascular diseases, such as myocardial infarction (MI) and stroke, remain controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) over three decades to evaluate the association between B-vitamin combinations and mortality and arterial thrombotic outcomes. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for RCTs with minimal duration over 24 months published between January 1996 and November 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Random-effects models were used in this meta-analysis to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Results: Thirteen randomized trials enrolling 68,363 participants across both primary and secondary prevention populations were included. B-vitamin combinations were associated with a nonsignificant reduction in stroke and 3-point major adverse cardiovascular events (MACE) (stroke: RR 0.91, 95% CI 0.81-1.04; MACE: RR 0.93, 95% CI 0.86-1.01). No significant effects were observed for all-cause mortality (RR 1.01, 95% CI 0.96-1.06), cardiovascular mortality (RR 0.97, 95% CI 0.88-1.07), or MI (RR 0.97, 95% CI 0.91-1.03). In primary prevention populations, B-vitamin combinations were associated with significant reductions in stroke (RR 0.79, 95% CI 0.68-0.93) and MACE (RR 0.80, 95% CI 0.69-0.92). A modest reduction in MACE was also observed in secondary prevention populations (RR 0.91, 95% CI 0.83-0.99). Between-study heterogeneity was minimal to low for ischemic outcomes, supporting the robustness of these estimates, whereas substantial heterogeneity was observed for mortality outcomes in secondary prevention populations. Conclusions: The evidence is limited by heterogeneity in trial populations, vitamin formulations and doses, and outcome definitions, with substantial between-study inconsistency for mortality outcomes and imprecision in subgroup estimates derived from a small number of contributing trials. Overall, B-vitamin combinations d

OBJECTIVE: Hyperhomocysteinemia (Hcy) independently predicts coronary heart disease (CHD) and adverse cardiovascular events. Although folic acid plays a key role in Hcy metabolism, the effect of combined B-vitamin supplementation (folic acid, VB6, and VB12) on clinical outcomes in CHD remains uncertain. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted from inception through April 2025 using MeSH terms including "folic acid," "vitamin B6," "vitamin B12," "coronary heart disease," and "homocysteine." A random-effects model was used for meta-analysis. RESULTS: Thirteen studies involving 14,539 participants were included in the meta-analysis (7,338 patients treated with folic acid combined with vitamin B complex and 7,301 controls). Combined B-vitamin supplementation significantly reduced serum Hcy levels [mean difference: -2.36; 95% confidence interval (CI): (-3.09 to -1.62); p < 0.01] compared with any single-nutrient regimen. The incidence of vascular restenosis was lower in the intervention group than in the control group (risk ratio: 0.65; 95% CI: 0.44-0.95; p < 0.05). However, no significant differences were observed in the incidence of major cardiovascular events (p = 0.78) or cardiovascular-related mortality (risk ratio: 0.96; 95% CI: 0.85-1.07; p = 0.44). CONCLUSION: Combined B-vitamin supplementation effectively lowers serum Hcy levels and the incidence of vascular restenosis in patients with CHD. However, its impact on cardiovascular events and mortality remains inconclusive. Plain Language Summary: Meta-analysis of 13 RCTs (n = 14,539): combined B vitamins lower serum HcyCombined B-vitamin supplementation lowers vascular restenosis in CHD patientsExerts no significant impact on major CV events or mortalityHcy-lowering appears CHD-specific; broader CV benefits remain unproven.

Update of doi: 10.1002/14651858.CD015464. RATIONALE: Higher blood pressure is strongly related to an increased risk of cardiovascular disease. There has been interest in riboflavin (vitamin B2) as a potential intervention to lower blood pressure, particularly for those with a common genetic polymorphism in the methylene tetrahydrofolate reductase enzyme (MTHFR). OBJECTIVES: To assess the benefits and harms of riboflavin supplements compared to placebo or no additional treatment for lowering systolic and diastolic blood pressure. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, Clarivate Web of Science, Clarivate Food Science & Technology Abstracts and two clinical trials registries. There were no restrictions on language, publication year, or publication status. The latest search date was 24 October 2024. We also handsearched the reference lists of included studies. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) conducted in adults that evaluated oral riboflavin supplements compared with an inactive control (e.g. placebo or no additional treatment) and measured at least one of the critical outcomes. We did not include trials that evaluated multivitamins containing riboflavin. Participants in both the intervention and control groups were able to receive standard medical therapy for hypertension prior to and during the trial. OUTCOMES: The critical outcomes were systolic blood pressure and diastolic blood pressure. The important outcomes were antihypertensive medication, adverse events and biomarkers of riboflavin status. RISK OF BIAS: We used the Cochrane RoB 2 tool to assess the risk of bias in included studies for the following outcomes: systolic blood pressure, diastolic blood pressure, antihypertensive medication and adverse events. SYNTHESIS METHODS: We used standard Cochrane methods. For the critical outcomes, which were continuous, we calculated mean differences (MD) and 95% confidence intervals (CIs). We used a fixed-effect meta-analysis to pool data for each outcome where possible. We conducted subgroup analyses, inc

CONTEXT: Elevated homocysteine levels are associated with brain atrophy and dementia, with B vitamin supplementation a possible low-cost intervention to help mitigate the deleterious impacts on brain health. However, prior meta-analyses have produced inconsistent results, with unexplained heterogeneity, while the quality of evidence has not been assessed. OBJECTIVE: This systematic review, meta-analysis, and meta-regression sought to quantify the effect of B vitamin supplementation on global cognitive function in older adults. DATA SOURCES: PubMed, Embase, PsychInfo, Scopus, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) from inception to June 20, 2024. DATA EXTRACTION: Eligible RCTs were derived from populations aged ≥60 years, with interventions of 26 weeks or longer comprising vitamin(s) B6, B9, or B12 of any dose or administration route, compared with placebo or usual dementia care. Studies must also have quantified global cognitive function at baseline and at end of treatment. DATA ANALYSIS: Seventeen RCTs, including 5275 participants, were identified. A small to moderate improvement (Hedges' g = 0.423; 95% CI: 0.188 to 0.657) in global cognitive function after supplementation was observed with considerable heterogeneity (I2 = 92.71; Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] = very low certainty). A meta-regression identified that statistical outliers and single-blinded studies contributed to the pooled g and heterogeneity. Omitting these studies resulted in a small effect (g = 0.110; 95% CI: 0.034 to 0.186), with negligible heterogeneity (I2 = 15.39; GRADE = high certainty). The effect size did not differ between classifications of cognitive impairment (ie, intact cognition, mild cognitive impairment, and dementia) in subgroup analysis (P = .729). CONCLUSION: The pooled findings indicated there is high-certainty evidence that vitamin B6, B9, or B12 supplementation has a very small benefit on global cognitive function in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42024553717. © The Author(s) 2025. Published by Oxford University Press on behalf of th

Recently, there has been an increasing interest in how diet and nutrition influence both physical and mental health. Numerous studies have highlighted the potential role of B vitamins in neuropsychiatric disorders (NPDs), yet the exact causal relationship between these nutrients and NPDs remains unclear. In our Mendelian randomization (MR) meta-analysis, we examined the links between B vitamins (VB6, VB12, and folate) and NPDs, utilizing data from previous MR studies, the UK Biobank, and FinnGen databases. Our MR analysis revealed a complex, multifaceted association: VB6 appears to protect against Alzheimer's disease (AD) but may increase the risk for conditions such as major depressive disorder and post-traumatic stress disorder. VB12 seems protective against autism spectrum disorder (ASD) but may heighten the risk for bipolar disorder (BD). Folate has shown protective effects against AD and intellectual disability (ID). The meta-analysis suggests that B vitamins may protect against certain disorders like AD and Parkinson's disease, but they might also be risk factors for anxiety and other psychiatric conditions. Further subgroup analysis indicates that VB6 protects against epilepsy and schizophrenia but increases the risk of mania; VB12 protects against ID and ASD but raises the risk of schizophrenia and BD; folate protects against schizophrenia, AD, and ID. These findings reveal the intricate influence of B vitamins on mental health, emphasizing that different B vitamins have distinct impacts on various NPDs. This complexity underscores the importance of personalized supplementation in developing future therapeutic approaches for NPDs.

The policies regarding the mandatory fortification of food with folic acid (FA) may impact the effectiveness of folate-based B vitamin treatment on cognitive function in older adults. We critically and systematically review the literature to assess whether food fortification policies affect folate-based B vitamin treatment efficacy on cognition function in older adults. Electronic databases, including PubMed, Web of Science, and CNKI, were searched for "Cognitive Function", "Folate", and "Older Adults". The study had specific criteria for inclusion, which were as follows: (1) the studies should initially have randomized controlled trials that were conducted on older adults aged 60 or above; (2) the studies must assess the relationship between folate status and cognitive performance; and (3) the studies should clarify the policies regarding food fortification with FA. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Two reviewers independently extracted all the data, and any discrepancies were resolved by consensus. All the data collected were compiled, compared, and analyzed critically. Random effects models were used to assess the effects of interventions. The systematic review included fifty-one articles involving 42,768 participants. Of these, the 23 articles were included in the meta-analysis. The meta-analysis on the effects of folate-based B vitamin supplementation on cognitive function showed a significant overall impact (Z = 3.84; p = 0.0001; SMD, 0.18; 95% CI, 0.09, 0.28). Further analysis revealed that FA food fortification policies were not implemented in countries where folate-based B vitamin supplementation improved cognitive impairment in older adults (Z = 3.75; p = 0.0002; SMD, 0.27; 95% CI, 0.13, 0.40). However, the FA intervention did not have significant outcomes in areas where FA food fortification policies were mandatory (Z = 0.75; p = 0.45; SMD, 0.03; 95% CI, -0.06, 0.13). Supplementing with oral folic acid, alone or in combination, has been linked to improved cognitive performance in older adults. While mandatory FA fortification has the improved folic acid status, ad

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508. © 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.

BACKGROUND: Chronic heart failure (CHF) has always posed a significant threat to human survival and health. The efficacy of thiamine supplementation in CHF patients remains uncertain. HYPOTHESIS: Receiving supplementary thiamine may not confer benefits to patients with CHF. METHODS: A comprehensive search was conducted across the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases up until May 2023 to identify articles investigating the effects of thiamine supplementation in CHF patients. Predefined criteria were utilized for selecting data on study characteristics and results. RESULTS: Seven randomized, double-blind, controlled trials (five parallel trials and two crossover trials) involving a total of 274 patients were enrolled. The results of the meta-analysis pooling these studies did not reveal any significant effect of thiamine treatment compared with placebo on left ventricular ejection fraction (WMD = 1.653%, 95% CI: -1.098 to 4.405, p = 0.239, I2 = 61.8%), left ventricular end-diastolic volume (WMD = -6.831 mL, 95% CI: -26.367 to 12.704, p = 0.493, I2 = 0.0%), 6-min walking test (WMD = 16.526 m, 95% CI: -36.582 to 69.634, p = 0.542, I2 = 66.3%), N-terminal pro-B type natriuretic peptide (WMD = 258.150 pg/mL, 95% CI: -236.406 to 752.707, p = 0.306, I2 = 21.6%), or New York Heart Association class (WMD = -0.223, 95% CI: -0.781 to 0.335, p = 0.434, I2 = 87.1%). However, it effectively improved the status of thiamine deficiency (TD). CONCLUSIONS: Our meta-analysis indicates that thiamine supplementation does not have a direct therapeutic effect on CHF, except for correcting TD. © 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.

This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.

BACKGROUND AND AIM: Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. METHODS: A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. RESULTS: A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). CONCLUSION: Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies ar

This prospective, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of thiamin and folic acid for cognitive impairment in maintenance hemodialysis (MHD) patients. A total of 215 MHD patients aged 18-75 with cognitive impairment were randomized to receive either oral thiamin (90 mg/day) plus folic acid (30 mg/day) or a placebo for 96 weeks. The primary endpoint was the change in the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog) score. After 96 weeks, the treatment group showed a significant improvement in ADAS-Cog scores (from 21.25 ± 9.2 to 15.07 ± 8.38, p < 0.001), whereas the placebo group showed a non‑significant improvement (from 24.53 ± 11.01 to 26.53 ± 14.43, p = 0.077). The treatment group also demonstrated significantly increased blood levels of thiamin (from 5.59 ± 0.95 to 18.21 ± 3.91 ng/mL) and folate (from 12.37 ± 4.62 to 63.33 ± 16.02 ng/mL), and a reduction in homocysteine levels (from 4709.06 ± 353.15 to 2962.68 ± 158.87 ng/mL, p < 0.001), with no significant changes in the placebo group. While mortality was similar between the two groups (12.1% vs. 12.0%, p = 0.978), the incidence of adverse events was significantly lower in the treatment group (31.8% vs. 62.0%, p = 0.0017), particularly cardiovascular and cerebrovascular events (13.1% vs. 25.9%, p = 0.001). The study concludes that combined thiamin and folic acid supplementation improves cognitive function in MHD patients with a favorable safety profile.

Paclitaxel being an effective treatment for ovarian cancer, presents one of the most critical toxicities; peripheral neuropathy (PN), a debilitating side effect that might limit continuation of chemotherapy. Vitamin B was found to significantly improve PN and Gabapentin is debatably used in chemotherapy induced peripheral neuropathy (CIPN). The aim of this study was to assess the efficacy of vitamin B prophylaxis in reducing the severity of CIPN, particularly in diabetic patients with the need for Gabapentin as additional therapy and the potential impact on disease response. A clinical trial of 146 adult ovarian cancer patients received Paclitaxel for 18 weeks; randomly allocated into two arms: One arm received vitamin B prophylaxis before starting Paclitaxel and other received upon CIPN. Gabapentin was given upon aggravation of CIPN. This study showed a significant reduction in CIPN grade over time, with fewer patients progressed to higher grades in prophylactic versus non-prophylactic group, extended to significant improvement in CIPN in prophylactic versus non-prophylactic diabetic patients. Gabapentin was more significantly required in non-prophylactic versus prophylactic group. A significant correlation was found between dose modification due to CIPN and CA125 status. Finally, a significant difference in PFS between prophylactic and non-prophylactic group was found at the end of the study. These results reinforce the potential role of vitamin B prophylaxis in improving patient outcomes through significantly reducing CIPN severity and minimizing the risk of dose reductions, thereby contributing to better disease response. Trial registration number: NCT07191587, date of registration: 09/24/2025, retrospectively registered. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

BACKGROUND AND OBJECTIVE: Chronic low back pain is one of the leading causes of disability. Current therapies offer limited efficacy and carry potential adverse risks. Vitamins B1, B6, and B12 have shown promise in the amelioration of musculoskeletal pain. The aim of this study was to evaluate the efficacy and safety of a combined injectable formulation of hydroxocobalamin (B12), thiamine hydrochloride (B1), and pyridoxine hydrochloride (B6) (TPH) as an adjunct treatment for chronic low back pain. METHODS: a randomized, double-blind, phase 3 clinical trial was conducted across six centers in Peru. A total of 163 patients with chronic mechanical lower back pain were included and assigned to receive TPH plus NSAIDs (n=81) or placebo plus NSAIDs (n=82). The primary outcome was the proportion of patients achieving ≥30% reduction in the NRS-11 score by day 28. Analyses were performed using an intention-to-treat approach and models adjusted for covariates. RESULTS: In the treatment group, 84% of participants achieved ≥30% reduction in the NRS-11 score compared to 64% in the control group (RR=1,31; 95% CI: 1,08-1,59; p=0,007). This effect remained significant after adjusting for BMI and albumin. Improvements were also observed in the Patient Global Assessment (PGA) and a favorable trend in the Oswestry Disability Index. The incidence of adverse events was higher in the treatment group, but no significant differences in serious events were found. CONCLUSION: TPH as an adjunct to standard treatment was effective in reducing chronic low back pain and demonstrated an acceptable safety profile.

BACKGROUND AND AIMS: We have evaluated the efficacy and tolerability of two food supplements (FS) containing flavonoids (naringin and hesperidin); same doses of B3, B6, B9 and B12 vitamins, and two different doses of a blend of Mentha spicata leaf extract and Amaranthus caudatus seed flour, in subjects with borderline high total (TC) and low-density lipoprotein cholesterol (LDL-C) levels. METHODS AND RESULTS: 114 Participants (18-70 years) with TC levels 200-239 mg/dL, (5.18-6.19 mmol/L) and LDL-C (<159 mg/dL) were randomised into three groups to receive for 90 days the lowest (n = 38, Treatment A), the highest dose of the FS (n = 38 - Treatment B), or placebo (n = 38). Treatment B was associated with a significant reduction in LDL-C (∼31.5 mg/dL;-22%) and TC (∼19.5 mg/dL; -9%), along with an increase in high-density lipoprotein cholesterol (HDL-C). The greater efficacy of Treatment B containing the highest dose of vegetable extracts is likely attributable to its higher M. spicata extract content, as judged by high-resolution mass spectrometry analysis of the preparation. CONCLUSION: The combination of different FS ingredients with different mechanisms of action can be a valuable strategy for improving lipid profiles in subjects with borderline high TC and LDL-C levels.

OBJECTIVE: The management of foot disorders often involves anti-inflammatory drugs for chronic inflammation and pain. Combining anti-inflammatory drugs with vitamin B complex may have a synergistic effect, but its efficacy in foot disorders remains unclear. This study aimed to investigate the effects of combining vitamin B complex with anti-inflammatory drugs in patients with foot disorders. METHODS: This study enrolled 201 patients aged ≥ 19 years with foot disorders of Achilles tendinitis, foot or ankle arthritis, Civinini-Morton syndrome (Morton's neuroma), or plantar fasciitis from four hospitals in Korea between October 2020 and December 2021. The patients were randomized in a 1:1 ratio to receive either aceclofenac 100 mg twice daily alone (control group, n = 77) or aceclofenac 100 mg and vitamin B complex twice daily (experimental group, n = 79) for 4 weeks. Among 201 randomized participants, 156 patients(79 in the experimental group and 77 in the control group) completed all scheduled follow-up visits and were included in the final analysis. The primary outcome measure was pain as assessed using the 10-cm visual analog scale (VAS). The secondary outcome measures were health-related quality of life and foot/ankle outcomes as assessed using the EuroQol 5 Dimension (EQ-5D) questionnaire and the Foot and Ankle Outcome Score (FAOS), respectively. RESULTS: VAS scores were more significantly reduced in the experimental group than in the control group, after 4 weeks (-2.87 ± 1.86 (from 6.95 ± 0.15 to 4.08 ± 0.17) vs. -0.91 ± 1.81 (from 5.99 ± 0.14 to 5.08 ± 0.21], p < 0.001). Similarly, improvements in the EQ-5D scores were significantly greater in the experimental group (0.079 ± 0.143 (from 0.69 ± 0.01 to 0.77 ± 0.01] vs 0.008 ± 0.111 (from 0.75 ± 0.01 to 0.76 ± 0.01], p = 0.001). Additionally, the increase in FAOS after treatment was significantly larger in the experimental group (9.94 ± 14.38 vs 2.97 ± 11.79, p = 0.001). Subgroup analysis revealed the combined therapy was particularly more effective in patients with chronic symptoms lasting over 3 months and in conditions like plantar fasciitis, foot or ankle arthritis, and Civinini-Morton syndrome. CONCLUSIO

BACKGROUND/AIMS: The neuroprotective effect of nicotinamide (NAM) supplementation has been demonstrated in both animal models and clinical trials. We conducted a trial to assess whether oral NAM improves retinal function in normal-tension glaucoma (NTG) participants receiving intraocular pressure (IOP)-lowering therapy. METHODS: Fifty-three NTG participants (untreated IOP ≤18 mm Hg) were enrolled in a double-masked, placebo-controlled crossover randomised clinical trial. Participants were randomly assigned to receive either oral placebo or NAM, followed by crossover without a washout period. Each treatment was administered for 12 weeks (NAM/placebo 1 g/day for 6 weeks, then 2 g/day for the subsequent 6 weeks). Retinal function was evaluated using full-field electroretinography and visual field testing. RESULTS: After 12 weeks, the amplitude changes of the photopic negative response in peak-to-trough (PhNRPT) and the B-wave were significantly greater in the NAM group (3.121±3.968 and 2.112±3.220 μV, respectively) compared with the placebo group (0.996±4.190 and 0.305±3.279 μV, respectively; p=0.045 and p=0.032). PhNRPT improved beyond twice the 95% coefficient of variation in 29.0% of the NAM group and 19.3% of the placebo group. No significant intergroup differences were observed in changes in mean deviation, pattern SD or visual field index after 12 weeks. CONCLUSION: Oral NAM supplementation in NTG participants induced functional improvement, as measured by PhNRPT and B-wave amplitude. Given that NTG is characterised by lower IOP, which may show a weaker correlation with electrophysiological activity and a slower progression rate compared with high-tension glaucoma, further long-term studies are needed to clarify the effects of NAM in this population. TRIAL REGISTRATION NUMBER: NCT06078605. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

Comment in JAMA. 2025 Oct 7;334(13):1147-1148. doi: 10.1001/jama.2025.14399. IMPORTANCE: Pregnant individuals with polycystic ovary syndrome (PCOS) present with a higher risk of pregnancy complications, including gestational diabetes, preeclampsia, and preterm birth. Myo-inositol supplementation may reduce these risks. OBJECTIVE: To determine whether daily supplementation with myo-inositol during pregnancy among individuals with PCOS reduces the risk of a composite outcome of gestational diabetes, preeclampsia, and preterm birth. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, randomized trial was conducted at 13 hospitals in the Netherlands. Pregnant individuals with PCOS who were between 8 and 16 weeks' gestation were enrolled between June 2019 and March 2023. Final follow-up was complete on December 27, 2023. Analyses were conducted July 2024. INTERVENTIONS: Participants were randomized on a 1:1 basis to receive sachets with either myo-inositol, 2 g, with 0.2 mg of folic acid twice daily (n = 230) or matching placebo with 0.2 mg of folic acid only (n = 234) until delivery. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of gestational diabetes, preeclampsia, or preterm birth (before 37 weeks' gestation). RESULTS: Among 464 participants, the mean (SD) age was 31.5 (3.8) years; 18 participants (3.9%) reported Asian race and 395 (86.1%) reported White race. The prevalence of biochemical hyperandrogenism was higher at baseline in the myo-inositol group than the placebo group (29.0% [53 of 180] vs 18.5% [37 of 193]). A primary outcome event occurred in 25.0% (n = 56) of participants in the myo-inositol group and 26.8% (n = 61) in the placebo group (relative risk, 0.93 [95% CI, 0.68-1.28]; P = .67). CONCLUSIONS AND RELEVANCE: Myo-inositol supplementation during pregnancy did not reduce the incidence of a composite of gestational diabetes, preeclampsia, or preterm birth in patients with PCOS. TRIAL REGISTRATION: onderzoekmetmensen.nl Identifier: NL67329.078.18.

BACKGROUND: Levetiracetam commonly causes neuropsychiatric adverse events (NPAEs) in pediatric patients, including irritability and aggression. This study evaluated pyridoxine supplementation for reducing levetiracetam-related NPAEs in children and adolescents with epilepsy. METHODS: We conducted a prospective, double-blind, randomized, placebo-controlled trial at Phramongkutklao Hospital, Thailand (January-June 2024). Participants aged 1-18 years with levetiracetam-related NPAEs were randomly assigned in a 1:1 ratio to receive either pyridoxine (10 mg/kg/day, maximum 200 mg) or placebo for 8 weeks. The primary outcome was change in behavioral symptoms using a validated 30-item questionnaire (score range 30-90). Secondary outcomes included treatment adherence, time to behavioral improvement, and adverse events. Sample size (n = 102) was calculated to detect a 20 % difference in behavioral improvement with 80 % power. RESULTS: 102 patients were randomized (pyridoxine n = 51, placebo n = 51). Baseline characteristics-including age, sex, seizure type, and number of concomitant ASMs-were comparable between groups. The mean age was 9.2 vs 8.3 years (p = 0.363), and 52.9 % vs 51.0 % were female in the pyridoxine and placebo groups, respectively. Most participants (56.9 %) were on dual therapy, with a median of two ASMs in both groups (p = 0.94). Both groups showed significant behavioral improvement over 8 weeks: the pyridoxine group from 14.79 ± 6.87 to 11.54 ± 6.22 (p < 0.001); placebo group from 15.65 ± 8.26 to 10.47 ± 8.22 (p < 0.001). No significant between-group difference existed at week 8 (p = 0.468). However, multivariate analysis of behavioral change scores from baseline to week 8 revealed significantly greater improvement in the pyridoxine group (adjusted OR = 2.31, 95 % CI: 1.15-4.63, p = 0.020). No serious adverse events occurred in either group. CONCLUSION: While pyridoxine did not significantly reduce behavioral scores compared to placebo at the study endpoint, the greater improvement in change scores over time suggests potential benefit in mitigating levetiracetam-associated NPAEs. Pyridoxine may serve as safe adjunctive therapy for patients who have be

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. © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

This study is conducted to investigate and contrast the effect of pyridoxine and ascorbic acid on mild cognitive impairment and quality of life in post-menopausal women. A randomized, controlled trial was carried out involving post-menopausal women with mild cognitive impairment. A total of 180 eligible participants were randomized to group A (25 mg of pyridoxine), group B (100 mg of ascorbic acid), and group C (not receiving any drug). The intervention time was 6 months. The Montreal cognitive assessment (MoCA) scale was utilized to assess cognitive function. Serum beta-amyloid (Aβ) 42 and homocysteine (Hcy) levels were measured. We used the menopause-specific quality of life (MENQOL) questionnaire to evaluate the quality of life (QOL) of post-menopausal women. Both pyridoxine and ascorbic acid have improved total MoCA scores (p = 0.0323 and p = 0.0074) compared to baseline. The Hcy level was reduced significantly in pyridoxine than in ascorbic acid (p = 0.0060). The serum Aβ 42 decreased significantly with pyridoxine and ascorbic acid (p = 0.0311 and p = 0.0042). In the MENQOL score, ascorbic acid has significantly reduced the score of the physical domain (p = 0.0020). However, a significant reduction in the overall score of MENQOL was not noticed before and after the treatment of pyridoxine and ascorbic acid (p = 0.3724 and p = 0.0732). Pyridoxine is more effective than ascorbic acid in lowering Hcy levels among post-menopausal women. Pyridoxine and ascorbic acid have been shown to improve cognitive function, and further long-term research is imperative to validate these findings. The trial was registered in the Clinical Trial Registry of India and registration no. is CTRI/2023/03/051131. Registered on: 28/03/2023-trial registered prospectively. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Biofilm is one of the causes of pathogenic bacteria's resistance to drugs. Vitamins, essential for maintaining various physiological functions within the animal body, have been observed to influence biofilm inhibition. The vitamins A, C, D, E, K, B6, and B12 possess notable anti-biofilm activity against specific pathogens, which have been reported extensively over the last few years, highlighting their potential in combating microbial infections. Vitamins B and K possess anti-quorum-sensing effects, which also contribute to the reduction of virulence factor expression of pathogenic bacteria. Many research reports have identified the incremental effectiveness of antibiotics when combined with various vitamins against bacterial infections, demonstrating a synergistic relationship between vitamins and conventional antibiotics that enhances the efficacy of antibiotics against the biofilm-mediated drug resistance capacity of microbes. According to current research, many vitamins, including vitamin A, D, and K, are responsible for binding to key proteins involved in biofilm production. However, the mechanisms of action of vitamins in combination with antibiotics against microbes require further elucidation to compensate for the existing information gap. This comprehensive review highlights, for the first time, that the least toxic biological molecules, "vitamins," can potentially manage biofilm-related microbial infections and enhance the therapeutic options available to clinicians. Plain Language Summary: Biofilms are communities of bacteria and fungi that adhere to surfaces and form a protective layer, making infections difficult to treat. This slimy shield protects microbes from antibiotics and disinfectants, enabling them to survive on medical devices, human tissues, and food surfaces, leading to persistent infections and contamination. This review examines recent research on the potential use of vitamins A, B complex, C, D, E, and K to prevent or disrupt biofilms formed by harmful microbes. Vitamins, essential nutrients typically known for supporting overall health, have been found to interfere with biofilm formation or help break down established biofilms. For

Diabetic cognitive dysfunction (DCD) refers to the cognitive impairment observed in individuals with diabetes. Epidemiological studies have suggested that supplementation with n-3 polyunsaturated fatty acid (PUFA) or B vitamins may prevent the development of diabetic complications. Post hoc studies indicate a potential synergistic effect of n-3 PUFA and B vitamins in preventing cognitive impairment. However, the precise effect and underlying mechanism of this combination on DCD remain unclear. In case-control study, we compared fatty acid composition of erythrocyte membrane and serum homocysteine levels between diabetic individuals with and without DCD. We found that insufficient levels of n-3 PUFA, along with elevated serum homocysteine, significantly increase the risk of developing DCD. Treatment with a combination of fish oil, folate, and vitamin B12 improved cognitive impairment and aberrant neuronal morphology in streptozotocin-induced DCD mice. Folic acid and vitamin B12 enhanced the efficiency of exogenous docosahexaenoic acid (DHA) transportation to the brain by preventing the accumulation of homocysteine and S-adenosylhomocysteine, thereby inhibiting neuronal apoptosis in diabetic brains. Furthermore, folic acid and vitamin B12 supplementation can provide sufficient 5-methylcytosine for diabetic brains by promoting DNA methylation, while increased DHA levels maintain TET-mediated active DNA demethylation in diabetic brains through enhancing TET2 function. Overall, our study provides novel insights into molecular mechanisms underlying the synergistic preventive effects of the combined supplementation with fish oil, folic acid and vitamin B12 on DCD, suggests that combining n-3 PUFA and B vitamins could be a promising strategy for preventing DCD among individuals with diabetes.

Combination therapy offers a promising advantage because they target multiple pathways involved in the pathogenesis and progression of Alzheimer's disease. This study aimed to investigate the synergistic effect of donepezil and each of vitamin B12, vitamin B6 and vitamin B1 on aluminium chloride (AlCl3)-induced neurotoxicity in rats. Fifty-four rats were divided into nine groups of six. Group I received distilled water, group II-AlCl3 (100 mg/kg), group III- AlCl3 (100 mg/kg) + Donepezil (10 mg/kg), group IV-AlCl3(100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B12 (5 mg/kg), group V-AlCl3 (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B6 (5 mg/kg), group VI-AlCl3 (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B1 (5 mg/kg), group VII-AlCl3 (100 mg/kg) + Vitamin B12 (5 mg/kg), group VIII-AlCl3 (100 mg/kg) + Vitamin B6 (5 mg/kg), group IX-AlCl3 (100 mg/kg) + Vitamin B1 (5 mg/kg). Treatment lasted for 40 days. Biochemical analyses of the brain revealed that chronic administration of AlCl3 significantly increased the level of inflammatory cytokines, caspase 9, malondialdehyde, nitric oxide and acetylcholinesterase (AChE) activity, while causing a significant decrease in superoxide dismutase (SOD) activity, Nrf2, reduced glutathione, dopamine and norepinephrine. Results also showed that AlCl3 caused cognitive impairment as indicated by a reduction in the percentage alternation index and hypo-activity towards novel object in animals treated with AlCl3 only. Moreover, results from biochemical evaluations indicated that treatment with donepezil, B vitamins and combination of donepezil and B vitamins attenuated the deficits in dopamine, norepinephrine, Nrf2, SOD and reduced glutathione, while also reducing the elevated levels of malondialdehyde, nitric oxide, AChE, caspase 9 and inflammatory markers. These observations were corroborated by result of histopathological evaluation. The combination of donepezil and vitamin B12, B6 and B1 proved to be more effective than donepezil monotherapy. Donepezil conferred significant protection against AlCl3-induced neurotoxicity, however, the combination of donepezil and vitamin B12, vitamin B6 and Vitamin B1 significantly performed better i

110. Br J Haematol. 2021 Feb;192(4):788-792. doi: 10.1111/bjh.17313. Epub 2021 Jan 20. Nicotinamide (vitamin B3) treatment improves response to G-CSF in severe congenital neutropenia patients. Deordieva E(1), Shvets O(1), Voronin K(1), Maschan A(1), Welte K(2)(3), Skokowa J(3), Novichkova G(1), Shcherbina A(1). Author information: (1)Oncology and Immunology Ministry of Healthcare of Russian Federation, Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Moskva, Russia. (2)University Children's Hospital Tübingen, Tuebingen, Germany. (3)Department of Oncology, Hematology, Immunology, and Rheumatology, University Hospital Tübingen, Tuebingen, Germany. DOI: 10.1111/bjh.17313 PMID: 33471934 [Indexed for MEDLINE]

Evidence suggests that the antinociceptive activity of various drugs can be increased when administered in combination with B vitamins (BVs). The aim of this study was to examine the potential interaction between statins and BVs to counter nociception, the latter measured by the formalin test. Rats were orally administered atorvastatin (1, 3, 10 and 30 mg/kg), pravastatin (1, 3, 10 and 30 mg/kg), rosuvastatin (1, 3, 10 and 30 mg/kg), BVs (31, 56, 100 and 180 mg/kg) or calculated combinations of BVs with each drug. The effective dose 30 (ED30 ) was calculated for each statin and BVs and subjected to isobolographic analysis, thus finding the ED30 of the combinations. The antinociceptive experimental ED30 values for BVs administered with atorvastatin, pravastatin or rosuvastatin were 1.53 ± 0.38, 6.74 ± 0.04 and 4.26 ± 0.39, respectively, being lower (p < .05) than the corresponding theoretical ED30 : 28.02 ± 2.20, 28.17 ± 2.20 and 29.86 ± 2.21. Since BVs likely boost the antinociceptive effect of statins, these combinations could possibly be advantageous in pain management. © 2020 Wiley Periodicals, LLC.

Nearly 70% of older adults in the U.S. report using ≥1 dietary supplements (DSs) daily. While DSs may have health benefits, there is risk for toxicity or harmful drug-supplement interactions if not taken correctly. Older adults with chronic wounds who use DSs are at increased risk of adverse drug-supplement interactions because they usually have comorbidities requiring polypharmacy management. However, no studies have evaluated DS use in this population. The aim of this retrospective pilot study was to describe DS use by a sample of older adults (n = 40) with chronic venous leg ulcers (CVLUs) who participated in a clinical trial testing the effects of fish oil supplementation on wound healing. At baseline, study personnel assisted all participants in completing an electronic questionnaire about DS use. Descriptive statistics were used to characterize the data. Twenty-five of the 40 participants (62.5%) reported taking ≥1 DS daily. On average, DS users were 65.16 years (SD = 8.51) and the majority were men (64.0%), white (68.0%), and had at least some college education (72.0%). Fifteen (60.0%) reported taking 1-2 DSs/day, and 10 (40.0%) reported taking ≥3/day. The most frequently reported DSs used were multivitamin/mineral complex (60.0%), vitamin D (36.0%), vitamin B complex (28.0%) and calcium (28.0%). Reasons for using DSs were to maintain or improve health (44.0%), improve bone density (12%), and boost the immune system (12%). Supplement users reported consuming an average of 9.12 (SD = 6.46) prescription drugs daily and 21 (84.0%) reported ≥3 chronic health conditions. In summary, DS use in this sample of chronic wound patients was high. Moreover, DS users reported using multiple prescription drugs (2-23/day) concomitantly with DSs. While older adults with CVLUs may benefit from targeted DS therapy, monitoring their DS use to reduce risk for adverse drug-supplement interactions is best practice. © 2020 by the Wound Healing Society.

Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.

The NAD-dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD+ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX-resistant K562 cells (K562R) in a dose-dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX-induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX-induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase-3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1. © 2019 Wiley Periodicals, Inc.

We aimed to test the hypothesis that treatment with enalapril and folic acid is more effective in preventing new-onset proteinuria than enalapril alone among hypertensive patients. This is a post hoc analysis of the renal substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 13 071 eligible participants without proteinuria were randomized to receive a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n=6511) or 10-mg enalapril alone (n=6560). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. Secondary outcomes included a composite of the primary outcome and all-cause death and the annual rate of estimated glomerular filtration rate decline. After a median 4.4 years of treatment, the primary event occurred in 213 (3.9%) and 188 (3.5%) participants, respectively, in the enalapril and the enalapril-folic acid group (odds ratio, 0.90; 95% confidence interval, 0.74-1.11). However, among participants with diabetes mellitus at baseline, folic acid therapy resulted in a significant reduction in the risk for the primary event (3.7% in the enalapril-folic acid group versus 7.4% in the enalapril group; odds ratio, 0.48; 95% confidence interval, 0.29-0.81) and the composite event (odds ratio, 0.62; 95% confidence interval, 0.42-0.92) and a 55% slower annual rate of estimated glomerular filtration rate decline (0.5% versus 1.1% per year; P=0.002). Among those without diabetes mellitus at baseline, there were no between-group differences in all the outcomes. In conclusion, enalapril-folic acid therapy, compared with enalapril alone, significantly reduced the development of proteinuria in diabetic patients with hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.