NICEVIVA
MONOGRAPH SPEC LATEST 2026

Vitamin B6 (Pyridoxine)

VITAMINS · Evidence Monograph

Vitamin B6 (Pyridoxine) is an evidence-graded vitamins monograph evaluated across 53 peer-reviewed PubMed studies (5 meta-analyses, 0 systematic reviews, and 9 randomized controlled trials, encompassing n = 101,756 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 53 Studies
Meta-Analyses · Reviews 5 Meta · 0 Systematic Reviews
Randomized Trials (RCT) 9 RCTs (7 Double-Blind)
Cumulative Participants n = 101,756
Reported Trial Dosages 5 mg · 400 mg · 200 mg
Trial Duration Range 24 months · 90 days · 12 months
Reading Time ~27 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis (supported by 53 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (5 mg · 400 mg · 200 mg) over a structured 24 months evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Bioactive Coenzyme or Standardized Vitamin Form
Prioritize bioactive coenzyme forms (such as methylated B-vitamins or cholecalciferol D3) matched to water- or fat-soluble absorption pathways.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Steady daytime energy and correction of subclinical deficiency markers over 4–8 weeks.
Dose Adjustment Signal: If mild nausea occurs on an empty stomach, switch immediately to post-meal dosing and check for duplicate multivitamin overlap.
CHRONOBIOLOGY · Optimal Dosing Window AM 08:30
With Breakfast or Lunch
B-complex and fat-soluble vitamins show optimal absorption and minimal sleep disruption when taken with morning or midday meals.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary vitamins clinical efficacy (53 PubMed studies)
Quantitative biomarker & outcome analysis (31 studies with effect-size/sample data)
Randomized controlled trial verification (9 RCTs · 7 double-blind)
Systematic review & meta-analysis synthesis (5 meta-analyses · 0 reviews)
01

What Is Vitamin B6 (Pyridoxine) & Why Does Form Matter?

Vitamin B6 (Pyridoxine) is classified under VITAMINS and has been investigated across 53 peer-reviewed PubMed publications for its role in cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (5 mg, 400 mg, 200 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Vitamin B6 (Pyridoxine) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (9 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Vitamin B6 (Pyridoxine) acts on pathways governing cellular coenzyme synthesis, metabolic methylation, and micronutrient homeostasis. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Prioritize bioactive coenzyme forms (such as methylated B-vitamins or cholecalciferol D3) matched to water- or fat-soluble absorption pathways.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Vitamin B6 (Pyridoxine) an overall evidence rating of GRADE High (4.0 / 4.0) based on 53 PubMed studies: 5 meta-analyses, 0 systematic reviews, and 9 randomized controlled trials (7 double-blind, n = 101,756 total participants).

Representative peer-reviewed findings include: • PMID:1578225 (1992) — "Chemical and in vivo studies of interaction between cadmium and vitamin B6." (Although the analysis of the metal burden in some organs seems to suggest a light increase of the cadmium level in the liver, this change has no significance at a statistical level.) • PMID:25970567 (2015) — "Leg cramps." (CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics; anti-epileptic drugs; calcium salts; diltiazem; magnesium salts; multivitamin and mineral supplements; quinine; sodium chloride; stre) • PMID:20824826 (2010) — "WITHDRAWN: Interventions for nausea and vomiting in early pregnancy." (Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)OR Effect Size & 95% CI DistributionEstimate (95% CI)PMID 208248260.16 (0.08–0.33)PMID 145839140.16 (0.08–0.33)PMID 118695670.17 (0.13–0.21)PMID 107961550.17PMID 409138822.31 (1.15–4.63)PMID 426329324.040.2Null (1)5Metric: OR
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Bioactive Coenzyme or Standardized Vitamin Form. Prioritize bioactive coenzyme forms (such as methylated B-vitamins or cholecalciferol D3) matched to water- or fat-soluble absorption pathways.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 5 mg · 400 mg · 200 mg · 16 mg over 24 months · 90 days · 12 months · 6 months. Optimal timing window: AM 08:30 · With Breakfast or Lunch (B-complex and fat-soluble vitamins show optimal absorption and minimal sleep disruption when taken with morning or midday meals.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Steady daytime energy and correction of subclinical deficiency markers over 4–8 weeks.

Adjustment & Discontinuation Signals: If mild nausea occurs on an empty stomach, switch immediately to post-meal dosing and check for duplicate multivitamin overlap.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Vitamin B6 (Pyridoxine), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (AM 08:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (5 mg · 400 mg · 200 mg) and re-evaluate efficacy after 24 months.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (53 Studies) · 31 Quantitative Analyses

01
CLINICAL STUDY Journal of inorganic biochemistry (1992) PMID: 1578225 ↗
Chemical and in vivo studies of interaction between cadmium and vitamin B6.
Clinical Trial Synthesis 1992 Clinical Study published in Journal of inorganic biochemistry. Key conclusion: Although the analysis of the metal burden in some organs seems to suggest a light increase of the cadmium level in the liver, this change has no significance at a statistical level.
View Original PubMed Abstract ↓

The interaction of vitamin B6 pyridoxine with cadmium acetate in ethanolic solution has been studied. The new compound Cd(PN-H)(OOCCH3) (PN-H = pyridoxinato anion) was isolated and its structure studied in the solid state by IR and 13C and 113Cd CP/MAS NMR spectroscopies. The effect of pyridoxine on survival rate among male Sprague rats injected intraperitoneally with 5 mg CdCl2.H2O/kg was also investigated. Vitamin treatment seems to increase (Protocol C) or does not affect the cadmium lethality. Although the analysis of the metal burden in some organs seems to suggest a light increase of the cadmium level in the liver, this change has no significance at a statistical level.

02
CLINICAL STUDY BMJ clinical evidence (2015) PMID: 25970567 ↗
Leg cramps.
Clinical Trial Synthesis 2015 Systematic Review published in BMJ clinical evidence. Key conclusion: CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics; anti-epileptic drugs; calcium salts; diltiazem; magnesium salts; multivitamin and mineral supplements; quinine; sodium chloride; stre
View Original PubMed Abstract ↓

INTRODUCTION: Involuntary, localised leg cramps are common and typically affect the calf muscles at night. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for idiopathic leg cramps? What are the effects of treatments for leg cramps in pregnancy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 16 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics; anti-epileptic drugs; calcium salts; diltiazem; magnesium salts; multivitamin and mineral supplements; quinine; sodium chloride; stretching exercises; verapamil; vitamin B6 (pyridoxine); and vitamin E.

03
CLINICAL STUDY The Cochrane database of systematic reviews (2010) PMID: 20824826 ↗
WITHDRAWN: Interventions for nausea and vomiting in early pregnancy.
Clinical Trial Synthesis 2010 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews (OR 0.16). Key conclusion: Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea.
View Original PubMed Abstract ↓

BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting. OBJECTIVES: To assess the effects of different methods of treating nausea and vomiting in early pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (December 2002) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002). SELECTION CRITERIA: Randomised trials of any treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the trial quality and extracted the data independently. MAIN RESULTS: Twenty-eight trials met the inclusion criteria. For milder degrees of nausea and vomiting, 21 trials were included. These trials were of variable quality. Nausea treatments were: different antihistamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin), P6 acupressure and ginger. For hyperemesis gravidarum, seven trials were identified testing treatments with oral ginger root extract, oral or injected corticosteroids or injected adrenocorticotropic hormone (ACTH), intravenous diazepam and acupuncture. Based on 12 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.16, 95% confidence interval 0.08 to 0.33). AUTHORS' CONCLUSIONS: Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes from randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis gravidarum show any evidence of benefit. Evidence from observational studies suggests no evidence of teratogenicity from any of these treatments.

04
CLINICAL STUDY BMJ clinical evidence (2010) PMID: 21729335 ↗
Autism.
Clinical Trial Synthesis 2010 Systematic Review published in BMJ clinical evidence. Key conclusion: CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: applied behavioural analysis; auditory integration training; Autism Preschool Programme; casein-free diet; chelation; Child's Talk programme; cog
View Original PubMed Abstract ↓

INTRODUCTION: Evidence for the efficacy of treatments for autism has improved in recent years. In this systematic review the evidence for both drug and non-drug treatments is appraised and clinical guidance is provided for their use. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of early intensive multidisciplinary intervention programmes in children with autism? What are the effects of dietary interventions in children with autism? What are the effects of drug treatments in children with autism? What are the effects of non-drug treatments in children with autism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: applied behavioural analysis; auditory integration training; Autism Preschool Programme; casein-free diet; chelation; Child's Talk programme; cognitive behavioural therapy; digestive enzymes; EarlyBird programme; facilitated communication; Floortime therapy; gluten-free diet; immunoglobulins; melatonin; memantine; methylphenidate; More Than Words programme; music therapy; olanzapine; omega-3 fish oil; picture exchange communication system; Portage scheme; probiotics; relationship development interventions; risperidone; secretin; selective serotonin reuptake inhibitors (SSRIs); sensory integration training; social stories; social skills training; Son-Rise programme; TEACCH; vitamin A; vitamin B6 (pyridoxine) plus magnesium; and vitamin C.

05
CLINICAL STUDY The Cochrane database of systematic reviews (2003) PMID: 14584010 ↗
The effect of vitamin B6 on cognition.
Clinical Trial Synthesis 2003 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews; statistical significance reported at p = 0.00001 (MD 0.43). Key conclusion: SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2003 using the terms: vitamin B6, pyridoxine, pyridoxamine, pyridoxal.
View Original PubMed Abstract ↓

BACKGROUND: Micronutrient status can affect cognitive function at all ages. Vitamin deficiencies could influence memory function and might contribute to age-associated cognitive impairment and dementia. Vitamin B6, comprising three chemically distinct compounds pyridoxal, pyridoxamine, and pyridoxine, is involved in the regulation of mental function and mood. Vitamin B6 is also an essential homocysteine re-methylation cofactor, and deficiency is associated with increase in blood homocysteine levels. Homocysteine is a risk factor for cerebrovascular disease and may also have directly toxic effects on neurons of the central nervous system. Neuropsychiatric disorders including seizures, migraine, chronic pain and depression have been linked to vitamin B6 deficiency. Epidemiological studies indicate that poor vitamin B6 status is common among older people. Hyperhomocysteinaemia has been suggested as a cause or mechanism in the development Alzheimer's disease and other forms of dementia. Supplementation with B vitamins including vitamin B6 has been shown to reduce blood homocysteine levels. OBJECTIVES: To assess the efficacy of vitamin B6 supplementation in reducing the risk of developing cognitive impairment by older healthy people, or improving cognitive functioning of people with cognitive decline and dementia, whether or not vitamin B6 deficiency has been diagnosed. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2003 using the terms: vitamin B6, pyridoxine, pyridoxamine, pyridoxal. For relevant trials on healthy elderly people MEDLINE, EMBASE and CENTRAL were searched using the previously mentioned terms as well as the term cognit * SELECTION CRITERIA: All unconfounded, double-blind randomized controlled trials in which the intervention with vitamin B6 was compared with placebo for healthy older people or people with cognitive decline or dementia. The primary outcome of interest was the efficacy of vitamin B6 supplementation on cognitive function. DATA COLLECTION AND ANALYSIS: The two reviewers independently evaluated all studies identified as possibly meeting the criteria for inclusion. O

06
CLINICAL STUDY The Cochrane database of systematic reviews (2003) PMID: 14583914 ↗
Interventions for nausea and vomiting in early pregnancy.
Clinical Trial Synthesis 2003 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews (OR 0.16). Key conclusion: Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea.
View Original PubMed Abstract ↓

BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting. OBJECTIVES: To assess the effects of different methods of treating nausea and vomiting in early pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (December 2002) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002). SELECTION CRITERIA: Randomised trials of any treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the trial quality and extracted the data independently. MAIN RESULTS: Twenty-eight trials met the inclusion criteria. For milder degrees of nausea and vomiting, 21 trials were included. These trials were of variable quality. Nausea treatments were: different antihistamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin), P6 acupressure and ginger. For hyperemesis gravidarum, seven trials were identified testing treatments with oral ginger root extract, oral or injected corticosteroids or injected adrenocorticotropic hormone (ACTH), intravenous diazepam and acupuncture. Based on 12 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.16, 95% confidence interval 0.08 to 0.33). REVIEWER'S CONCLUSIONS: Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes from randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis gravidarum show any evidence of benefit. Evidence from observational studies suggests no evidence of teratogenicity from any of these treatments.

07
CLINICAL STUDY The Cochrane database of systematic reviews (2002) PMID: 11869567 ↗
Interventions for nausea and vomiting in early pregnancy.
Clinical Trial Synthesis 2002 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews (OR 0.17). Key conclusion: Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea.
View Original PubMed Abstract ↓

BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting. OBJECTIVES: The objective of this review was to assess the effects of different methods of treating nausea and vomiting in early pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of last search: October 2001. SELECTION CRITERIA: Randomised trials of any treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Twenty-three trials were included. These trials were of variable quality. Nausea treatments were different anti-histamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin) and P6 acupressure. For hyperemesis gravidarum five trials were identified testing treatments with oral ginger root extract, oral corticosteroids or injected adrenocorticotropic hormone (ACTH) and intravenous diazepam. Based on 13 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.17, 95% confidence interval 0.13 to 0.21). REVIEWER'S CONCLUSIONS: Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes from randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis gravidarum show any evidence of benefit. Evidence from observational studies suggests no evidence of teratogenicity from any of these treatments.

08
CLINICAL STUDY The Cochrane database of systematic reviews (2000) PMID: 10796155 ↗
Interventions for nausea and vomiting in early pregnancy.
Clinical Trial Synthesis 2000 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews (OR 0.17). Key conclusion: Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea.
View Original PubMed Abstract ↓

BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting. OBJECTIVES: The objective of this review was to assess the effects of different methods of treating nausea and vomiting in early pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Randomised trials of any treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Twenty trials were included. These trials were of variable quality. Nausea treatments were different anti-histamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin) and P6 acupressure. For hyperemesis gravidarum two trials were identified using treatments with ginger root and ACTH (adrenocorticotropic hormone) injections. Based on 13 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.17, 95% confidence interval 0. 13 to 0.21). REVIEWER'S CONCLUSIONS: Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. The results of the trial using adrenocorticotropic hormone to treat hyperemesis gravidarum show no evidence of benefit. Ginger may be of benefit, but the evidence so far is weak.

09
META-ANALYSIS Nutrients (2026) PMID: 41830012 ↗
Complex Effects of B-Vitamin Combinations on Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials over Three Decades.
Clinical Trial Synthesis 2026 Meta-Analysis published in Nutrients involving n = 68,363 participants (RR 0.91). Key conclusion: 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 contributi
View Original PubMed Abstract ↓

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

10
META-ANALYSIS Annals of medicine (2026) PMID: 41615824 ↗
Combined B-vitamin supplementation on homocysteine and vascular outcomes in coronary heart disease: a meta-analysis.
Clinical Trial Synthesis 2026 Meta-Analysis published in Annals of medicine involving n = 14,539 participants; statistical significance reported at p = 0.01 (RR 0.65). Key conclusion: 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
View Original PubMed Abstract ↓

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.

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