Thiamine

Evidence Fact Sheet

Vitamin B1

Thiamine (vitamin B1) is an essential water-soluble vitamin whose active form (thiamine pyrophosphate) is a coenzyme for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and transketolase in energy metabolism. Research doses run from the 1.1-1.4 mg/day RDA to 25-100 mg/day supplements; ICU, sepsis, cardiac-arrest and Alzheimer's trials are largely null. GRAS/EFSA-authorized.

Also known as: Vitamin B1 · Thiamin · Aneurine · Thiamine hydrochloride · Thiamine mononitrate · Benfotiamine (fat-soluble derivative)

Overview

Thiamine (vitamin B1) is an essential water-soluble vitamin whose active form, thiamine pyrophosphate (TPP), serves as the coenzyme for pyruvate dehydrogenase, the alpha-ketoglutarate dehydrogenase complex and transketolase — enzymes central to carbohydrate-derived energy metabolism and nervous-system function. Dietary reference intakes sit at roughly 1.1-1.4 mg/day for deficiency prevention, while common oral supplements supply about 25-100 mg/day; benfotiamine, a fat-soluble derivative, is studied at higher research-grade doses and is regulated separately. Because excess water-soluble thiamine is excreted renally, no Tolerable Upper Intake Level has been set. It is GRAS in the US (21 CFR 184.1875/184.1878), an EFSA-permitted vitamin carrying four authorized Article 13.1 health claims (energy metabolism, nervous system, heart, psychological function), and a permitted nutrient under China GB standards and Brazil's ANVISA framework. Much of the strongest human evidence comes from critical-illness, sepsis, cardiac-arrest and dementia trials, where pooled and randomized results are frequently null.

Mechanism of Action

Active form thiamine pyrophosphate (TPP) is the coenzyme for pyruvate dehydrogenase, driving entry of carbohydrate-derived pyruvate into the TCA cycle · Cofactor for the alpha-ketoglutarate dehydrogenase complex within the TCA cycle (oxidative energy metabolism) · Cofactor for transketolase in the pentose phosphate pathway (NADPH regeneration and ribose-5-phosphate supply) · Cofactor for the branched-chain alpha-keto acid dehydrogenase complex (BCAA catabolism) · Mechanistic studies describe TPP-dependent flux as essential for normal energy-yielding metabolism and nervous-system function

Body systems: Neurological & Cognitive · Mitochondrial & Cellular Energy · METABOLISM · Cardiovascular · Musculoskeletal

Evidence-Based Benefits

Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Thiamine is not characterized as a treatment for any disease.

Critical Illness / ICU Outcomes

Meta-analysis supported

P = .03serum creatinine · lower
P = .71all-cause mortality · null

A meta-analysis of 8 randomized trials in intensive-care patients found that thiamine supplementation modestly lowered serum creatinine (and more so in patients over 60), but produced no measurable benefit on lactate, all-cause mortality, need for renal replacement therapy, or ICU length of stay. This is a nuanced result: one biochemical marker moved while the hard clinical outcomes did not.

Reported effect: Reduced serum creatinine (P = .03); no difference in lactate (P = .26), all-cause mortality (P = .71), renal replacement therapy (P = .14), or ICU length of stay (P = .39)

“thiamine supplementation reduced the serum creatinine level (P = .03) ... no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P = .26). ... Thiamine supplementation did not decrease the risk of all-cause mortality (P = .71).”

Source: PMID 37553224 · Karimi 2024 · Nutrition Reviews

Sepsis / Septic Shock — Longer-Term Mortality

Null / no benefit Meta-analysis supported

10 RCTslonger-term mortality
7,096 patientspooled cohort

A component network meta-analysis of adjunctive vitamin C, glucocorticoids and vitamin B1 in sepsis or septic shock found no significant differences in longer-term mortality between any of the treatments and placebo or usual care. Thiamine was evaluated within combination and individual regimens rather than as an isolated effect estimate, and the certainty of evidence ranged from moderate to very low.

Reported effect: No significant difference in longer-term mortality (10 RCTs, 7,096 patients; moderate to very-low-certainty)

“There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty).”

Source: PMID 34750650 · Fujii 2022 · Intensive Care Med

Thiamine + Vitamin C in Sepsis — Mortality

Null / no benefit Meta-analysis supported

OR 1.11in-hospital mortality
0.79-1.5695% CI · P = 0.55
7 RCTs868 patients

A meta-analysis of seven randomized trials (868 patients) testing thiamine combined with vitamin C in sepsis or septic shock found no in-hospital mortality benefit. The combination was associated with some improvement in SOFA scores and vasopressor duration, but these did not translate into a survival difference.

Reported effect: In-hospital mortality OR 1.11 (95% CI 0.79-1.56; P = 0.55), 7 RCTs / 868 patients

“There was no statistical difference between groups for in-hospital mortality (OR: 1.11; 95% CI [0.79-1.56]; P = 0.55).”

Source: PMID 33709993 · Ge 2021 · Eur J Emerg Med

Cognition / Alzheimer's Disease (Benfotiamine)

Null / no benefit RCT supported

34 vs 36benfotiamine vs placebo
p = 0.125ADAS-Cog · not significant
43% lowerADAS-Cog rise (NS)

In a Phase IIa randomized placebo-controlled trial, the fat-soluble thiamine derivative benfotiamine showed a 43% smaller rise in ADAS-Cog (the primary cognitive-decline measure) versus placebo, directionally favoring treatment — but the result did not reach statistical significance. The primary endpoint was therefore null. Benfotiamine is a distinct derivative, not equivalent to standard water-soluble thiamine supplements.

Reported effect: ADAS-Cog increase 43% lower with benfotiamine vs placebo, non-significant (p = 0.125); n = 34 benfotiamine, 36 placebo

“The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125).”

Source: PMID 33074237 · Gibson 2020 · J Alzheimers Dis

Cardiac Arrest — Metabolic Resuscitation

Null / no benefit RCT supported

36 patientsenrollment · stopped early
MD 1.5 mmol/L48-h lactate · 95% CI -3.1-6.1
p = 0.88primary endpoint · null

A randomized trial of thiamine as a metabolic resuscitator after in-hospital cardiac arrest was stopped after 36 patients because a Data Safety and Monitoring Board flagged potential harm in an unplanned subgroup analysis. Thiamine showed no overall effect on the primary endpoint of lactate at 48 hours. This is a prominent honest negative for a high-interest acute-care use.

Reported effect: No difference in 48-hour lactate: mean difference 1.5 mmol/L (95% CI -3.1-6.1), global p = 0.88; enrollment stopped at 36 patients

“There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88). ... Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis.”

Source: PMID 38428722 · Berg 2024 · Resuscitation

Dosage (research context · not a recommendation)

RDA/RNI 1.1-1.4 mg/day (deficiency prevention; women 1.1 mg, men 1.2 mg US RDA; China RNI 1.2-1.4 mg). Common oral supplement / energy-metabolism doses 25-100 mg/day (DSLD median 100 mg/day across 38 products). Exercise-fatigue research used ~100 mg/day oral thiamine over a short pre-exercise loading period (~3 days · Suzuki 1996 PMID 8815395). Benfotiamine (fat-soluble derivative, ~5x bioavailability) research doses 300-1050 mg/day are study-grade and outside routine supplement use. No Tolerable Upper Intake Level set for oral water-soluble thiamine (excess excreted in urine).

Regulatory Status · 4 Markets

US · FDA: GRAS by regulation — 21 CFR 184.1875 (Thiamine HCl) and 21 CFR 184.1878 (Thiamine mononitrate); lawful dietary supplement ingredient; structure/function claims permitted with the mandatory FDA disclaimer (statement not evaluated by FDA; not intended to diagnose, treat, cure, or prevent disease). Daily Value 1.2 mg.
EU · EFSA: Permitted vitamin under Directive 2002/46/EC Annex I; 4 authorized Art. 13.1 health claims under Reg 432/2012 (energy-yielding metabolism, nervous system, function of the heart, psychological function), usable verbatim when the food/supplement is at least a 'source of thiamine' per Reg 1924/2006. NRV 1.1 mg; DRV 0.1 mg/MJ.
CN · China: Established nutrient — SAMR-permitted vitamin B1 source (thiamine HCl / thiamine mononitrate) under GB 14880 food-fortifier and GB 2760 standards; usable in health foods and general food fortification (NRV 1.4 mg/day; adult RNI 1.2-1.4 mg/day). Benfotiamine (fat-soluble derivative) requires separate filing.
BR · ANVISA: Permitted vitamin under RDC 269/2005 and the RDC 243/2018 supplement framework; daily maximum amounts regulated by IN 28/2018; functional claims must use ANVISA-approved wording. Benfotiamine is not on the RDC 269 vitamin positive list and requires separate compliance review for high-dose formulas.

Authorized Claims

EFSA — “Thiamine contributes to normal energy-yielding metabolism” (Reg (EU) 432/2012 Annex)

EFSA — “Thiamine contributes to normal energy-yielding metabolism” (Reg 432/2012)

EFSA — “Thiamine contributes to the normal functioning of the nervous system” (Reg 432/2012)

EFSA — “Thiamine contributes to the normal function of the heart” (Reg 432/2012)

EFSA — “Thiamine contributes to normal psychological function” (Reg 432/2012)

Safety

Water-soluble thiamine has a very wide safety margin with no established Tolerable Upper Intake Level — excess is excreted renally and oral toxicity is clinically very rare. Allergy to thiamine is extremely uncommon. Benfotiamine is fat-soluble and reaches markedly higher plasma levels; long-term data at ≥300 mg/day are limited and such doses are research-grade. Thiaminases in some raw freshwater fish and certain fermented teas, and polyphenols in tea, can reduce B1 absorption. Suspected Wernicke encephalopathy is a medical emergency requiring IV/IM thiamine under clinical care and cannot be substituted by oral supplements (informational only, not a product claim).

Goals: cognitive-support · heart-health

Lifestyles: senior-60-plus

References

PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.

PMID 37553224 · Karimi 2024 · Nutrition Reviews — Critical Illness / ICU Outcomes
PMID 34750650 · Fujii 2022 · Intensive Care Med — Sepsis / Septic Shock — Longer-Term Mortality
PMID 33709993 · Ge 2021 · Eur J Emerg Med — Thiamine + Vitamin C in Sepsis — Mortality
PMID 33074237 · Gibson 2020 · J Alzheimers Dis — Cognition / Alzheimer's Disease (Benfotiamine)
PMID 38428722 · Berg 2024 · Resuscitation — Cardiac Arrest — Metabolic Resuscitation

Frequently Asked Questions

1. What does thiamine (vitamin B1) actually do in the body?

Thiamine's active form, thiamine pyrophosphate, is a coenzyme for pyruvate dehydrogenase, the alpha-ketoglutarate dehydrogenase complex and transketolase — enzymes that drive carbohydrate-derived energy metabolism and support normal nervous-system function. These mechanistic roles underpin the four EFSA-authorized health claims (energy-yielding metabolism, nervous system, heart, psychological function).

2. How much thiamine do studies and supplements typically use?

Dietary reference intakes are about 1.1-1.4 mg/day for deficiency prevention, while common oral supplements supply roughly 25-100 mg/day. Benfotiamine, a fat-soluble derivative used in some research (such as the Gibson 2020 Alzheimer's trial), is dosed higher and regulated separately. Because excess water-soluble thiamine is excreted in urine, no Tolerable Upper Intake Level has been set.

3. Does thiamine help in sepsis, ICU care, or cardiac arrest?

The strongest human evidence here is largely null. A component network meta-analysis (Fujii 2022, 10 RCTs, 7,096 patients) found no longer-term mortality benefit in sepsis, a thiamine-plus-vitamin-C meta-analysis (Ge 2021) showed no in-hospital mortality difference (OR 1.11), and a cardiac-arrest RCT (Berg 2024) found no effect on 48-hour lactate (p = 0.88) and was stopped early. An ICU meta-analysis (Karimi 2024) lowered serum creatinine (P = .03) but did not change mortality (P = .71). These are research findings in critically ill populations, not evidence that supplements treat these conditions.

4. Is the Alzheimer's / cognition evidence positive?

Not on the primary endpoint. In the Gibson 2020 Phase IIa trial, the fat-soluble derivative benfotiamine produced a 43% smaller rise in ADAS-Cog versus placebo — directionally favorable — but the effect did not reach statistical significance (p = 0.125), so the primary cognitive outcome was null. Benfotiamine is also a distinct derivative rather than standard water-soluble thiamine.

Last evidence review: 2026-06-13

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