B vitamins (vitamin B6, vitamin B12, folate)
Also called pyridoxine, folic acid, vitamin B9, cyanocobalamin, methylcobalamin, L-5-methyltetrahydrofolate. Vitamins (B group).
Bottom line
Vitamins B6, B12 and folate are B vitamins, and UK and EU registers authorize the claim that B6 and B12 contribute to normal energy-yielding metabolism [25][26]. Reviews of placebo-controlled trials, mostly in older adults, found these supplements probably have little or no effect on overall cognition [1][2]. High-dose vitamin B6 is linked to sensory nerve damage [11][13].
- The UK and EU registers authorize the wording "contributes to normal energy-yielding metabolism" for vitamin B6 and vitamin B12, on foods that are at least a source of the vitamin [25][26].
- A Cochrane review of 14 trials with 27,882 participants found that folic acid, vitamin B12, vitamin B6 or combinations probably have little or no effect on global cognition in cognitively healthy adults, mostly over 60 and many with a history of heart or blood-vessel disease [1].
- In a meta-analysis co-funded by Bayer HealthCare, supplements containing at least three B vitamins improved stress ratings slightly in healthy and at-risk adults (SMD 0.23), with no clear effect on symptoms of low mood or anxiety [8].
- EFSA set an upper level of 12 mg a day for vitamin B6 in 2023 because of peripheral neuropathy, while the US upper level set in 1998 is 100 mg a day [11][22].
- Health Canada's multivitamin monograph added a nerve-symptom risk statement for products with 10 mg or more of vitamin B6 in 2026, and Australia requires a label warning on listed medicines above 10 mg [28][30].
Evidence by outcome
| Outcome | Grade | Basis | Modifiers | Rationale |
|---|---|---|---|---|
| Perceived stress | C Limited | Meta-analysis positive with a lower confidence bound near zero, pooling healthy and at-risk adults, and evidence only for multi-ingredient B-complex products; two of the three supporting sources were funded by Bayer. a conservative grader would choose C over B | Industry-fundedSubjective outcome onlyShort-term only | Why C grade for Perceived stress: explainedApproved of the Perceived stress grade |
| Mood | C Limited, no effect found | Three meta-analyses null or non-significant on mood-symptom scales, with a positive trend in one; mixed small trials. C, none; N not proposed because the B-complex meta-analysis trends positive (p = 0.07) | Subjective outcome only | Why C grade for Mood: explainedApproved of the Mood grade |
| Global cognition | C Limited, no effect found | Meta-analyses conflict: null in cognitively healthy older adults and in an 11-trial collaboration, a very small benefit in later analyses that pool people with and without cognitive impairment; older-only evidence caps at C and mixed direction gives C, none. Not N because a 2025 high-certainty estimate is positive | Why C grade for Global cognition: explainedApproved of the Global cognition grade | |
| Memory | C Limited, no effect found | One positive RCT on a secondary endpoint in a selected population against null pooled domain analyses; not B because the positive result is not a prespecified primary outcome, and not N because the large RCT is positive | Why C grade for Memory: explainedApproved of the Memory grade |
Grades describe evidence for each outcome, not a recommendation. Open a grade for its rationale and dated grade history. How we grade
Most trials enrolled older adults and many tested combinations rather than one vitamin [1][6][8]. The evidence grading method explains each grade.
Do B vitamins improve overall cognition?
Evidence is mixed, and the largest analyses found little or no effect [1][2]. A 2018 Cochrane review pooled 14 placebo-controlled trials of these vitamins with 27,882 participants [1]. Most participants were over 60 and had a history of heart or blood-vessel disease, and the reviewers concluded that B vitamins probably have little or no effect on global cognitive function up to 5 years and may have none at 5-10 years [1].
The B-Vitamin Treatment Trialists' Collaboration combined 11 large trials with 22,000 participants, mostly testing folic acid with vitamin B12 [2]. Across the 7 trials with end-of-treatment global tests (20,431 people), there was no significant effect on global cognitive function [2].
Two later meta-analyses point to a very small benefit [3][4]. A 2025 meta-analysis of 17 trials with 5,275 adults aged 60 or older, testing vitamin B6, B9 (folate) or B12 for at least 26 weeks, first found a pooled effect of g = 0.423 (Hedges' g, a standardized effect size), but results varied widely between trials and certainty was very low [3]. After the reviewers removed trials with unusually extreme results and single-blind trials (blinded on one side only), results were consistent and the effect was small (g = 0.110, high certainty); it did not differ by cognitive status [3]. A 2022 meta-analysis of 25 trials, which also included observational studies, found Mini-Mental State Examination (MMSE) score changes 0.14 points better with B vitamins in its trial analysis (6,155 participants) [4]. Both pooled populations with and without cognitive impairment, so results may not apply to healthy adults. A 2024 meta-analysis of trials in adults aged 60 or older found a small overall benefit of folate-based B vitamins (SMD 0.18), but none in places where folic acid fortification of food is mandatory (SMD 0.03) [20].
A 2021 meta-analysis of 16 trials with 6,276 participants without overt B12 deficiency, using at least 100 mcg of vitamin B12 a day, found no evidence of an effect of B12 alone or B complex on any area of cognitive function [5].
Do B vitamins improve memory?
Evidence is mixed [2][5][6]. In the FACIT trial, 818 Dutch adults aged 50-70 with raised homocysteine and normal vitamin B12 took 800 µg of folic acid or placebo daily for 3 years [6]. The folic acid group's 3-year change in memory was better than placebo (difference in Z scores 0.132) [6]. Cognition was a secondary endpoint [6].
A post hoc analysis of 791 FACIT participants found folic acid's effect on global cognition was larger in people with low omega-3 fatty acid levels, but found no such interaction for episodic memory [7].
Pooled analyses did not find a memory effect [2][5]. In the 4 cognitive-domain trials of the Clarke meta-analysis (1,340 people, mean 2.3 years), B vitamins containing folic acid had no significant effect on any individual domain, including memory [2]. The B12 meta-analysis found no effect of B12 alone or B complex on any cognitive subdomain [5], and a 2024 meta-analysis of 8 vitamin B12 trials found no effect on memory [21].
Do B vitamins affect perceived stress?
Slightly, in trials of multi-ingredient products [8][9]. A 2019 meta-analysis of daily supplements with at least three B vitamins for at least four weeks included 18 articles (16 trials, 2,015 participants), including multivitamins [8]. In healthy and "at-risk" adults, it found a small benefit for stress (958 participants, SMD 0.23, 95% CI 0.02 to 0.45) [8]. The review was co-funded by Bayer HealthCare, and three authors have received research funding and honoraria from the nutrition and supplement industry [8].
In a 33-day trial funded by Bayer Consumer Care, 215 employed men aged 30 to 55 who took a B-complex product with vitamin C and minerals rated their stress better on the Perceived Stress Scale than those on placebo [9]. The effect cannot be assigned to the B vitamins alone [9]. In a 3-month trial of 60 workers reporting chronic work stress, those taking a high-dose vitamin B complex reported lower personal strain after 12 weeks [10].
Do B vitamins affect mood?
Not clearly [5][8][21]. In the Bayer-co-funded meta-analysis, the benefit for symptoms of low mood did not reach significance (568 participants, SMD 0.15, p = 0.07), and there was no effect on anxiety (SMD 0.03) [8]. Two meta-analyses of vitamin B12 alone or with other B vitamins found no overall effect on low-mood symptom measures [5][21]. The work-stress trial found less dejected mood but no change in other mood measures [10].
What the evidence does not show
On fatigue, the B12 meta-analysis found too few trials to analyze [5], and one Bayer-funded combination-product trial found men felt less mentally tired [9]. The energy hub lists graded energy outcomes for other compounds.
Doses used in studies
Ranges researchers used, not dosing advice. Bars share one scale. Read our disclaimer.
folic acid 800 µg/day for 3 years
at least 100 mcg/day, oral or intramuscular
at least three B vitamins daily for at least four weeks
Timing and form
Health Canada's monograph lists cyanocobalamin, hydroxocobalamin and methylcobalamin among vitamin B12 sources, and folic acid and L-5-methyltetrahydrofolate among folate sources [28]. In the Clarke trials, all but one used folic acid, and one used 5-methyltetrahydrofolate [2].
Form matters for limits. The US folate upper level applies to folate from supplements, fortified foods or both [22].
What it is
Vitamin B6, also known as pyridoxine, vitamin B12 and folate are three of the B vitamins. NHS guidance says people should be able to get the vitamin B6 and folate they need from their diet, and that people who eat meat, fish or dairy foods should be able to get enough vitamin B12 [24]. Folate is the form found in foods, and folic acid is the manufactured form [24].
The UK and EU registers allow foods that are at least a source of the vitamin to say that "Vitamin B6 contributes to normal energy-yielding metabolism" and that "Vitamin B12 contributes to normal energy-yielding metabolism" [25][26]. In the GB register, folate, B6 and B12 each also carry the authorized claim that they contribute "to the reduction of tiredness and fatigue" [25]. When the US Institute of Medicine set intake values for these vitamins in 1998, it wrote that there is no observable health benefit beyond preventing the signs and symptoms of deficiency [22].
Some groups are more likely to run low on vitamin B12. The NIH Office of Dietary Supplements (ODS) lists older adults, people who have had gastrointestinal surgery and people who follow vegetarian diets, and reports that between 3% and 43% of community-dwelling older adults have vitamin B12 deficiency on blood tests, depending on the definition used [32]. The Institute of Medicine advised adults over 50 to get most of their B12 from fortified foods or supplements [22].
How they work (mechanism, not an effect on any outcome): folic acid, alone or with vitamin B12, lowers blood homocysteine [2][6], and raised homocysteine is associated with poorer cognitive performance in the general population [6].
Safety and interactions
Safety flag. EFSA describes the link between excess vitamin B6 and peripheral neuropathy as well established and set an adult upper level of 12 mg a day [11]. A systematic review found high B6 levels, usually from supplements, may lead to a mainly sensory neuropathy, with reported improvement after stopping pyridoxine [13]. A 2026 census found 5.1% of 11,367 adult US products directed 100 mg of vitamin B6 a day or more [14]. Folic acid above 1 mg a day can mask the symptoms of vitamin B12 deficiency, according to NHS guidance [24]; EFSA based its folic acid upper level on this risk [12]. No upper level has been set for vitamin B12 because of a lack of suitable data [22].
Who sources say should be careful.
- People taking high-dose vitamin B6. Canadian multivitamins with 10 mg or more must tell users to stop and ask a practitioner if numbness, tingling or pain develops [28]; Australian listed medicines above 10 mg carry a similar warning [30].
- People with low vitamin B12, especially older adults, taking high-dose folic acid, because of the masking concern described under safety [12][24].
- People taking metformin, acid-lowering medicines, antiepileptic medicines, levodopa, methotrexate or sulfasalazine, as described under interactions [15][16][18][19][34].
Vitamin B6 at high doses can damage sensory nerves [11][13]. EFSA describes the link between excess vitamin B6 and peripheral neuropathy as well established [11]. A systematic review of 20 articles found that higher B6 levels, usually from supplements, may lead to a mainly sensory neuropathy, and that people reported improvement after stopping pyridoxine [13]. ODS reports that 1-6 g of pyridoxine a day for 12-40 months can cause severe, progressive sensory neuropathy, and that symptoms usually stop if supplements are stopped as soon as they appear [31]. NHS guidance says 200 mg or more a day can cause loss of feeling in the arms and legs, and that the effect of 10 mg to 200 mg is unclear [24].
Upper intake levels differ by market. EFSA identified a reference point of 50 mg a day from a case-control study and set the adult upper level at 12 mg a day [11]. The 1998 US upper level is 100 mg a day for adults [22]. A 2026 census of US supplement labels found 5.1% of 11,367 adult products directed 100 mg a day or more, and 38.7% exceeded 12 mg a day; 56.2% of the products at or above 100 mg were not sold as vitamin B6 or B-complex products [14].
Table: Upper intake levels and supplement limits for adults, by market (checked November 11, 2026)
| Market | Vitamin B6 | Folic acid | Vitamin B12 | Source |
|---|---|---|---|---|
| US | Upper level 100 mg a day | Upper level 1,000 µg a day (supplements and fortified foods) | No upper level set | [22] |
| UK | DHSC advises no more than 10 mg a day from supplements unless a doctor advises it | 1 mg or less a day unlikely to cause harm | 2 mg or less a day unlikely to cause harm | [24] |
| EU | Upper level 12 mg a day (2023) | Upper level 1,000 µg a day (retained in 2023), for folic acid and the authorized 5-methyltetrahydrofolate salts combined | Not stated in the sources we checked | [11][12] |
| Canada | Licensed multivitamins: up to 100 mg a day; risk statement at 10 mg or more | Up to 1,000 µg a day | Up to 1,000 µg a day | [28] |
| Australia | Listed medicines: up to 100 mg a day; label warning above 10 mg | Not stated in the sources we checked | Not stated in the sources we checked | [30] |
The Institute of Medicine could not set an upper level for vitamin B12 because of a lack of suitable data, and said this does not mean people can tolerate chronic intakes above the recommended amount [22].
High folic acid can hide low vitamin B12 [12][24]. NHS guidance says folic acid above 1 mg a day can mask the symptoms of vitamin B12 deficiency, which can damage the nervous system if missed, a particular concern for older people [24]. EFSA based its folic acid upper level on the progression of nerve symptoms in people with B12 deficiency [12], as the Institute of Medicine did [22].
The Cochrane review noted very sparse data on adverse effects in the cognition trials [1]; see our glossary for adverse event and upper intake level.
Pregnancy
The UK Department of Health and Social Care recommends folic acid supplements for all women who are pregnant or could get pregnant [24]. Health Canada's monograph tells users to ask a health care practitioner whether they would benefit from additional folate [28].
Interactions sources report
Some medicines lower vitamin B12 levels [15][16][17]. In a meta-analysis of 6 randomized trials in people with type 2 diabetes or polycystic ovary syndrome, those taking metformin had serum vitamin B12 levels 53.93 pmol/L lower than those on placebo or rosiglitazone, possibly depending on dose [15]. In a case-control study of 25,956 people with vitamin B12 deficiency and 184,199 without, 2 or more years' supply of proton pump inhibitors (OR 1.65) or H2 blockers (OR 1.25) was associated with deficiency [16]. A meta-analysis of five observational studies linked long-term use of acid-lowering medicines to B12 deficiency (hazard ratio 1.83) [17].
Folate and medicines for seizures interact in both directions [18][33]. A review of human studies reports that phenytoin lowers serum folate, and that folic acid given to folate-deficient people with epilepsy usually lowers phenytoin levels, with a possible return of seizures [18]. ODS says antiepileptic medicines such as phenytoin, carbamazepine and valproate can reduce folate levels, and that folate supplements might lower levels of these medicines [33]. ODS's vitamin B6 fact sheet adds that 200 mg a day of pyridoxine lowered phenytoin and phenobarbital levels in some research [31].
Vitamin B6 and levodopa interact. The US prescribing information for carbidopa-levodopa tablets says pyridoxine at 10 mg to 25 mg may counteract the effects of levodopa, and that carbidopa blocks this [34]. It adds that carbidopa-levodopa may lower vitamin B6 levels, and that seizures linked to B6 deficiency have been reported [34].
ODS describes methotrexate as a folate antagonist and says sulfasalazine inhibits folate absorption and can cause deficiency [33]. In a Cochrane review of people taking low-dose methotrexate for rheumatoid arthritis, a clinical population, folic or folinic acid reduced gastrointestinal side effects by 26% in relative terms and did not appear to change methotrexate's effect on the condition [19].
These sources describe what has been reported, not what is right for any individual. If you take any of these medicines, talk to your doctor or pharmacist before combining them with vitamin B6, vitamin B12 or folate supplements.
Regulatory status
| Market | Status | Notes |
|---|---|---|
| US | No FDA statement specific to vitamin B6, vitamin B12 or folate found as of November 11, 2026. Under DSHEA, firms are responsible for the safety and labeling of their products before marketing, and FDA can act against adulterated or misbranded products afterward. US upper levels (IOM 1998): B6 100 mg/day, folate 1,000 µg/day from supplements and fortified foods, none set for B12. | |
| UK | GB NHC register (spreadsheet of May 19, 2026) authorizes 'contributes to normal energy-yielding metabolism' for vitamin B6 and vitamin B12, for foods that are at least a source. DHSC advice via the NHS: no more than 10 mg of vitamin B6 a day in supplements unless advised by a doctor. | |
| EU | Directive 2002/46/EC lists vitamin B6, folic acid and vitamin B12 for food supplements; Regulation (EU) No 432/2012 authorizes the energy-yielding metabolism claims for B6 and B12. EFSA upper levels (2023): B6 12 mg/day; folic acid 1,000 µg/day, applying to combined intake of folic acid and the authorized 5-methyltetrahydrofolate glucosamine and calcium salts. | |
| Canada | Multi-vitamin/mineral products are licensable under Health Canada's monograph (June 26, 2026): adult maximums B6 100 mg, B12 1,000 µg, folate 1,000 µg a day; risk statement for B6 at 10 mg or more after a March 2026 summary safety review. | |
| Australia | Poisons Standard (October 2026): pyridoxine, pyridoxal and pyridoxamine are Schedule 4 (prescription only) except oral preparations of 50 mg or less per daily dose, or more than 50 mg up to 200 mg with required advisory statements. Listed medicines: up to 100 mg pyridoxine a day for adults, mandatory warning above 10 mg. |
FAQ
Does vitamin B12 give you energy?
The UK and EU registers authorize the wording 'Vitamin B12 contributes to normal energy-yielding metabolism' for foods that are at least a source of B12 [25][26]. When it set intake values for the B vitamins in 1998, the Institute of Medicine wrote that there is no observable health benefit beyond preventing the signs and symptoms of deficiency [22], and a B12 meta-analysis found too few fatigue trials to analyze [5].
What is the upper limit for vitamin B6?
It depends on the market. The US upper level is 100 mg a day for adults [22], EFSA set 12 mg a day in 2023 [11], and UK government advice is no more than 10 mg a day from supplements unless a doctor advises it [24]. Canada requires a nerve-symptom warning at 10 mg or more, and Australia above 10 mg [28][30].
Can folic acid hide a vitamin B12 deficiency?
NHS guidance says folic acid above 1 mg a day can mask the symptoms of vitamin B12 deficiency, which can damage the nervous system if missed [24]. EFSA based its folic acid upper level of 1,000 µg a day on this risk [12].
References
- Rutjes AW, Denton DA, Di Nisio M, et al. Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life. Cochrane Database Syst Rev. 2018.
- Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014.
- Berg J, Grant R, Siervo M, et al. Efficacy of B Vitamin Supplementation on Global Cognitive Function in Older Adults: A Systematic Review and Meta-analysis. Nutr Rev. 2025.
- Wang Z, Zhu W, Xing Y, et al. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022.
- Markun S, Gravestock I, Jäger L, et al. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients. 2021.
- Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007.
- van Soest APM, van de Rest O, Witkamp RF, et al. Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial. Am J Clin Nutr. 2021.
- Young LM, Pipingas A, White DJ, et al. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals. Nutrients. 2019.
- Kennedy DO, Veasey R, Watson A, et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology (Berl). 2010.
- Stough C, Scholey A, Lloyd J, et al. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. 2011.
- EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, et al. Scientific opinion on the tolerable upper intake level for vitamin B6. EFSA J. 2023.
- EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA Panel), Turck D, Bohn T, et al. Scientific opinion on the tolerable upper intake level for folate. EFSA J. 2023.
- Muhamad R, Akrivaki A, Papagiannopoulou G, et al. The Role of Vitamin B6 in Peripheral Neuropathy: A Systematic Review. Nutrients. 2023.
- Staiger B. Vitamin B6 Doses on United States Dietary Supplement Labels Relative to the Tolerable Upper Intake Level: A Census of the National Institutes of Health Dietary Supplement Label Database. Cureus. 2026.
- Liu Q, Li S, Quan H, et al. Vitamin B12 status in metformin treated patients: systematic review. PLoS One. 2014.
- Lam JR, Schneider JL, Zhao W, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013.
- Jung SB, Nagaraja V, Kapur A, et al. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis. Intern Med J. 2015.
- Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother. 1995.
- Shea B, Swinden MV, Tanjong Ghogomu E, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013.
- Zhang L, Chen X, Chen Y, et al. A Comparative Study Evaluating the Effectiveness of Folate-Based B Vitamin Intervention on Cognitive Function of Older Adults under Mandatory Folic Acid Fortification Policy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2024.
- Alzahrani H. Assessment of Vitamin B12 Efficacy on Cognitive Memory Function and Depressive Symptoms: A Systematic Review and Meta-Analysis. Cureus. 2024.
- Institute of Medicine (National Academies). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline: Summary. 1998.
- U.S. Food and Drug Administration. Dietary Supplements. Updated October 1, 2024.
- NHS. Vitamins and minerals: B vitamins and folic acid. Updated August 3, 2020.
- GOV.UK (Department of Health and Social Care). Great Britain nutrition and health claims (NHC) register, spreadsheet of 19 May 2026. Updated May 19, 2026.
- EUR-Lex (European Union). Commission Regulation (EU) No 432/2012, consolidated text of 17 May 2021 (list of permitted health claims). Updated May 17, 2021.
- EUR-Lex (European Union). Directive 2002/46/EC on the approximation of the laws of the Member States relating to food supplements (original text). Updated June 10, 2002.
- Health Canada, Natural and Non-prescription Health Products Directorate. Multi-vitamin/mineral supplements monograph. Updated June 26, 2026.
- Australian Government, Department of Health, Disability and Ageing (Federal Register of Legislation). Therapeutic Goods (Poisons Standard—October 2026) Instrument 2026 (F2026L01327). Updated September 30, 2026.
- Australian Government, Department of Health, Disability and Ageing (Federal Register of Legislation). Therapeutic Goods (Permissible Ingredients) Determination (No. 3) 2026 (F2026L01382). Updated October 13, 2026.
- NIH Office of Dietary Supplements. Vitamin B6: Fact Sheet for Health Professionals. Updated June 16, 2023.
- NIH Office of Dietary Supplements. Vitamin B12: Fact Sheet for Health Professionals. Updated July 2, 2025.
- NIH Office of Dietary Supplements. Folate: Fact Sheet for Health Professionals. Updated November 30, 2022.
- U.S. Food and Drug Administration (via DailyMed, National Library of Medicine). SINEMET (carbidopa and levodopa) tablets: prescribing information (Organon LLC). Updated August 24, 2026.