Supplements

Thiamine & Benfotiamine

Updated · 44 sources

Thiamine, also called vitamin B1, is an essential water-soluble vitamin that the body needs to turn food into usable energy. Benfotiamine is a synthetic derivative, made from thiamine hydrochloride, that the body converts back to thiamine. It is sold as a supplement in the US and as a medicine in some European countries. This page covers both, but their evidence is very different, so we keep them separate throughout.

Thiamine has a proven medical use. Its deficiency causes beriberi and Wernicke-Korsakoff syndrome, and thiamine hydrochloride injection is an FDA-approved prescription treatment. Benfotiamine raises blood thiamine more than ordinary thiamine salts do, but that has not reliably translated into clinical benefit. Its longest placebo-controlled trials in diabetic neuropathy found no effect on nerve outcomes. In October 2026, the European Food Safety Authority (EFSA) concluded that the safety of benfotiamine as a novel food at up to 300 mg/day could not be established, mainly because of data gaps.

This page summarizes what the FDA label, the NIH Office of Dietary Supplements, EFSA, guidelines and clinical trials report. It is for education only and is not medical advice.

Property Detail
Type Thiamine: essential vitamin, also a prescription injectable. Benfotiamine: synthetic S-acyl thiamine derivative
Adult RDA (thiamine) 1.2 mg/day for men; 1.1 mg/day for women; 1.4 mg/day in pregnancy and lactation
Upper limit (thiamine) None set in the US or EU. We found no established limit for benfotiamine
Common forms Thiamine hydrochloride and thiamine mononitrate; benfotiamine in some supplements
Approved drug use Thiamine hydrochloride injection (100 mg/mL, IM or slow IV) for deficiency and beriberi
Benfotiamine trial doses 300–900 mg/day in most trials; up to 1,200 mg/day in a phase I study
Half-life, thiamine Free thiamine about 96 min after IV and 154 min after oral dosing; thiamine diphosphate about 11 h (6 healthy adults)
Half-life, after benfotiamine Thiamine in blood about 6–14 h; thiamine diphosphate about 19–48 h (healthy adults, by dose)
Serious rare risk Anaphylaxis with injected thiamine; label reports deaths
WADA status Neither form is named on the 2026 Prohibited List

What it is

Thiamine is built from a pyrimidine ring and a thiazole ring joined by a methylene bridge (EFSA 2026). The adult body holds only about 25–30 mg, stored mainly in the liver in small amounts. About 80% of that is thiamine diphosphate (TDP, also called thiamine pyrophosphate), the main active form (NIH ODS).

TDP is a required helper (cofactor) for five enzymes in glucose, amino acid and lipid metabolism, including transketolase (NIH ODS). The label notes that the requirement rises when a diet is higher in carbohydrate, and that body depletion can occur after about three weeks without any thiamine (FDA label).

Form What it is Where it appears
Free thiamine Unphosphorylated vitamin Plant foods; the form absorbed in the gut
TMP, TDP, TTP Thiamine with one, two or three phosphates Animal foods and body tissues; TDP is the active cofactor
Thiamine hydrochloride Stable, water-soluble salt Supplements and the prescription injection
Thiamine mononitrate Stable, water-soluble salt Supplements
Benfotiamine Synthetic S-benzoylthiamine O-monophosphate, 466.45 g/mol, with an open thiazole ring Supplements in the US; medicines in Germany and Austria
Disulfide derivatives Lipid-soluble derivatives such as sulbutiamine A separate chemical class from benfotiamine

These details come from the NIH ODS, EFSA 2026 and Volvert et al., BMC Pharmacol 2008.

About “fat-soluble vitamin B1.” Benfotiamine is routinely called lipid-soluble, and some older trial papers call it an allithiamine. Volvert and colleagues reported that it is practically insoluble in water, organic solvents and oil, and that it is an S-acyl compound with a different pharmacological profile from the true lipid-soluble disulfide derivatives. EFSA attributes its passive absorption to the open thiazole ring, not to dissolving in fat.

Which evidence applies to which form

Question Thiamine Benfotiamine
Treats deficiency, beriberi, Wernicke encephalopathy Yes; FDA-labeled injection and guideline treatment Not labeled in the US; we found no trial in Wernicke encephalopathy
Raises blood thiamine Yes; oral absorption is less efficient at higher intakes Yes, to a greater degree after oral dosing
Diabetic neuropathy Not tested in the trials cited here Short symptom trials mixed; 12- and 24-month trials found no effect
Diabetic kidney disease One positive 40-person pilot (300 mg/day) One negative 82-person trial (900 mg/day)
Alzheimer’s disease Three very small trials, no conclusion possible Phase IIa trial missed its primary endpoint; phase II trial ongoing
Anaphylaxis signal Yes, with injections No reports found in the oral trials cited here

Pharmacokinetics

Thiamine is absorbed by active transport at nutritional doses and by passive diffusion at pharmacologic doses, and absorption efficiency falls at intakes over 5 mg/day. Excess is excreted in the urine (NIH ODS; EFSA 2026).

Benfotiamine takes a different route. Enzymes in the gut wall remove its phosphate to give S-benzoylthiamine, which crosses membranes passively and in a dose-dependent way. Hydrolysis then releases ordinary thiamine. The benzoyl group is converted to benzoic acid and then hippuric acid, which leaves in the urine and does not appear to accumulate (EFSA 2026). In other words, benfotiamine acts as a thiamine prodrug.

Measure Oral or IV thiamine Oral benfotiamine
Study 50 mg thiamine HCl IV and oral; 6 healthy adults (Tallaksen et al. 1993) 150–1,200 mg single doses; 150–600 mg multiple doses; healthy adults (Sheng et al. 2021)
Time to peak Plasma thiamine 53 min (oral) Thiamine 1–2 h; TMP 3.5–8 h; TDP 8–24 h (medians, whole blood)
Half-life Plasma thiamine 96 min (IV), 154 min (oral); TDP 664 min (IV) Thiamine 6.3–13.9 h; TDP 18.6–48.2 h (means by dose)
Urinary recovery 53% (IV) and 2.5% (oral) at 24 h Not compared here
Bioavailability Oral relative to IV: 5.3% See below
Accumulation Tissue stores rise two- to threefold when intake far exceeds need (FDA label) Thiamine accumulation ratio 1.96–2.11 after 7 days of multiple dosing

These two studies used different doses and methods, so the half-lives should not be read as a head-to-head comparison.

The main direct comparison is a crossover study of 20 healthy young men, who took 300 mg of benfotiamine or an equimolar 220 mg of thiamine HCl. Relative to thiamine HCl, the bioavailability from benfotiamine was 1,147.3 ± 490.3% for plasma thiamine and 195.8 ± 33.8% for red-cell TDP (Xie et al., J Clin Pharmacol 2014). The much smaller gain in TDP matters, because TDP is the active form.

EFSA accepted that benfotiamine is bioavailable, can serve as a thiamine source and is more bioavailable than water-soluble forms. It also found the data insufficient to derive a conversion factor, noting that Xie and colleagues studied only men and only one dose (EFSA 2026). No validated figure therefore exists for how much benfotiamine equals a given amount of thiamine in effect. By molar equivalence, the 300 mg/day dose proposed to EFSA corresponds to about 170 mg of thiamine, which is more than 100 times the European reference intake.

Does benfotiamine reach the brain?

The animal data conflict. In mice, oral benfotiamine raised thiamine derivatives in blood and liver but not in brain (Volvert et al. 2008). In a rat model of neurodegeneration, 150 mg/kg for 30 days raised TDP in the hippocampus and entorhinal cortex (Moraes et al., Exp Gerontol 2020). Neither result can be applied directly to people.

Requirements and food sources

The US Food and Nutrition Board values, as listed by the ODS, apply to thiamine (NIH ODS):

Group Male (mg/day) Female (mg/day)
0–6 months (AI) 0.2 0.2
7–12 months (AI) 0.3 0.3
1–3 years 0.5 0.5
4–8 years 0.6 0.6
9–13 years 0.9 0.9
14–18 years 1.2 1.0
19 years and older 1.2 1.1
Pregnancy and lactation (ages 14–50) — 1.4

The RDA (Recommended Dietary Allowance) covers nearly all healthy people; the AI (Adequate Intake) is used when evidence is too thin to set an RDA. Because thiamine needs track energy intake, EFSA instead sets a reference intake of 0.1 mg per megajoule, or about 0.68–1.4 mg/day for adults (EFSA 2026).

Whole grains, meat and fish are natural sources, and US breads, cereals and infant formulas are fortified. Examples from the ODS table include a fortified breakfast cereal at 1.2 mg per serving, and pork chop, trout and black beans at 0.4 mg per serving. Dairy and most fruits contain little. Heating and processing reduce thiamine, and unenriched white rice has about one-tenth the thiamine of brown rice.

In US survey data from 2003–2006, 6% of the population had usual intakes below the estimated average requirement. Adults averaged 1.95 mg/day (men) and 1.39 mg/day (women) from food, and about 4.9 mg/day with supplements. Typical multivitamins provide about 1.5 mg (NIH ODS).

Deficiency

Beriberi and Wernicke-Korsakoff syndrome

Early deficiency can cause weight loss, poor appetite, confusion, short-term memory loss, muscle weakness and cardiovascular symptoms. It can progress to these conditions (NIH ODS; FDA label):

  • Dry beriberi. Mainly nervous system symptoms, including peripheral neuropathy and wasting.
  • Wet beriberi. Mainly cardiovascular symptoms; it can cause heart failure with leg swelling and, occasionally, death. The label treats wet beriberi with heart failure as a cardiac emergency.
  • Wernicke encephalopathy. The acute, life-threatening brain stage. The European neurology guideline lists dietary deficiency, eye signs, cerebellar dysfunction, and altered mental state or mild memory impairment; two of the four are needed for diagnosis in people with alcohol use disorder (Galvin et al., Eur J Neurol 2010). The ODS reports that up to 20% of untreated patients die.
  • Korsakoff syndrome. A chronic state with severe short-term memory loss, disorientation and confabulation (confusion between real and imagined memories). Parenteral thiamine does not bring recovery in about one-quarter of patients at this stage.

Who is at risk

Group What the data show
Alcohol use disorder Up to 80% develop deficiency, because ethanol reduces absorption, liver stores and phosphorylation. Wernicke-Korsakoff syndrome is about 8–10 times more common than in the general population
Bariatric surgery Systematic review of 84 Wernicke cases: 94% were admitted within 6 months of surgery, 90% had frequent vomiting, 18% received IV glucose without thiamine and 49% recovered incompletely (Aasheim, Ann Surg 2008)
GLP-1 drugs 15 cases identified in one analysis, mostly with semaglutide or tirzepatide; reporting odds ratio 2.35 (95% CI 1.38–4.01) (Lev et al., Clin Nutr 2026)
Older adults Up to 20%–30% have laboratory signs of some deficiency
Diabetes 17%–79% have poor status by erythrocyte transketolase testing, varying by study
HIV/AIDS Autopsies of 380 people with AIDS found Wernicke encephalopathy in almost 10%
Heart failure 21%–98% have poor status, varying by study; diuretics are one possible contributor

Except where another source is named, these figures are from the NIH ODS.

The GLP-1 reports cannot show how often this occurs. A 2026 systematic review of six published cases of Wernicke encephalopathy after semaglutide found that all patients had prolonged gastrointestinal symptoms and substantial weight loss first, and that several outcomes were poor (Bidesie & Oudman, Obesity 2026). Tirzepatide was also represented in the Lev analysis.

Measuring status

Blood thiamine is not a reliable indicator of status. Erythrocyte transketolase activity with and without added TDP (the “TDP effect”) is commonly used: 0%–15% is typical in healthy people, 15%–25% suggests marginal deficiency and over 25% indicates deficiency. Urinary thiamine reflects intake rather than tissue stores; below 100 mcg/day suggests insufficient intake in adults and below 40 mcg/day an extremely low one (NIH ODS). EFSA regards whole-blood or red-cell TDP and the transketolase activity coefficient as good status markers (EFSA 2026).

Approved medical use: thiamine injection

Benfotiamine has no part in this section. In the US, thiamine hydrochloride injection is a generic prescription drug, with several manufacturers listed on DailyMed. The details below come from one current label, issued July 2026 (FDA label).

It is indicated for thiamine deficiency and beriberi. It is meant for when rapid restoration is needed, such as Wernicke encephalopathy, infantile beriberi with acute collapse, cardiovascular disease due to deficiency, or neuritis of pregnancy with severe vomiting. It is also indicated when IV dextrose is given to people with marginal thiamine status, to avoid precipitating heart failure, and when established deficiency cannot be treated orally.

Situation Labeled dose
Beriberi 10–20 mg IM three times daily for as long as 2 weeks, then an oral multivitamin with 5–10 mg daily for a month
Wet beriberi with heart failure Emergency treatment, given slowly by IV
Infantile beriberi with collapse 25 mg IV, cautiously
Neuritis of pregnancy with severe vomiting 5–10 mg IM daily
Wernicke-Korsakoff syndrome 100 mg IV initially, then 50–100 mg IM daily until eating a regular, balanced diet
Marginal status receiving IV dextrose 100 mg in each of the first few liters of IV fluid

Guideline doses are higher and the evidence is thin

Guideline doses for Wernicke encephalopathy go well beyond the label, and evidence for the exact dose is limited:

  • EFNS guideline (2010). 200 mg three times daily, preferably IV, given before any carbohydrate, for suspected or manifest disease. It also advises parenteral thiamine for all at-risk patients in the emergency room, and follow-up of thiamine status for at least 6 months after bariatric surgery. The dose recommendation is Level C, and the emergency-room advice is a good practice point rather than a trial-based finding (Galvin et al. 2010).
  • Cochrane review (2013). Only two trials qualified, one with usable data (107 participants, five IM doses for 2 days). The 200 mg/day dose beat 5 mg/day on a delayed alternation test (MD −17.90 trials, 95% CI −35.4 to −0.40), with no simple dose-response pattern. The review found the evidence insufficient to guide dose, frequency, route or duration (Day et al., Cochrane 2013).
  • Dose-comparison trials (2022). Two double-blind trials in people with alcohol misuse compared parenteral regimens. In 393 at-risk patients, 100 mg daily, 100 mg three times daily and 300 mg three times daily for 3 days did not differ. In 127 symptomatic patients, 100, 300 and 500 mg three times daily for 5 days did not differ. The authors noted that a medically complex population and cross-cultural testing may have complicated the results (Dingwall et al., Alcohol Clin Exp Res 2022).
  • Scoping review (2026). Across 26 studies, delayed treatment and use of oral thiamine in high-risk situations were repeatedly reported (Goldani et al., Addict Sci Clin Pract 2026).

The absence of a proven best dose does not mean that treatment is optional. Observational data link parenteral thiamine to a large fall in deaths from the syndrome (Dingwall et al. 2022). The ODS also notes that oral thiamine may not raise blood levels enough in high-risk patients.

Magnesium

Magnesium is a cofactor in thiamine-dependent reactions and transport (Ott & Werneke, Ther Adv Psychopharmacol 2020). A randomized trial in alcohol withdrawal analyzed 115 patients on IV thiamine, IV magnesium sulfate or both. Its primary endpoint, change in transketolase activity, did not differ between groups. Median time to initial symptom resolution was 10 h with thiamine alone, 5.5 h with both and 6 h with magnesium alone, and 59% of patients started with low magnesium. Nearly all patients (99%) already had normal or high red-cell TDP before treatment (Maguire et al., Sci Rep 2022).

What the research shows: benfotiamine

Why it was studied in diabetes

In diabetic animals, benfotiamine activated transketolase, blocked three pathways of high-glucose damage and prevented experimental retinopathy (Hammes et al., Nat Med 2003). The human trials tested whether that would carry over to people. In the longest ones, thiamine levels rose clearly while clinical outcomes did not.

Diabetic neuropathy

Trial Who Treatment Length Result
Stracke et al. 1996 24 people with diabetic polyneuropathy Benfotiamine plus vitamins B6 and B12 vs control 12 weeks Peroneal nerve conduction velocity improved (P = 0.006); vibration threshold showed a trend
BEDIP, Haupt et al. 2005 40 inpatients 400 mg/day vs placebo 3 weeks Neuropathy score improved (P = 0.0287), pain improved (P = 0.0414); tuning-fork test unchanged
BENDIP, Stracke et al. 2008 165 randomized; 133 analyzed by intention to treat 600 or 300 mg/day vs placebo 6 weeks Neuropathy Symptom Score: P = 0.055 by intention to treat, P = 0.033 per protocol; Total Symptom Score not different
Fraser et al. 2012 67 with type 1 diabetes 300 mg/day vs placebo 24 months No difference in nerve function or inflammatory markers, despite large rises in thiamine and TDP (both P under 0.001)
BOND, Ziegler et al. 2026 57 with type 2 diabetes and symptomatic polyneuropathy 600 mg/day (300 mg twice daily) vs placebo 12 months Primary endpoint unchanged (see below)

BOND is the most detailed trial so far. Its primary endpoint was corneal nerve fiber length, which changed by +0.559 mm/mm² with benfotiamine and +0.835 mm/mm² with placebo (treatment effect −0.327; 95% CI −2.432 to 1.778; P = 0.760). Skin biopsy, nerve conduction, autonomic tests, symptom scales and quality of life also showed no significant differences. Only the Neuropathy Symptom Score showed a trend (P = 0.098), even though all six thiamine measures rose.

Wörwag Pharma, maker of the study drug, sponsored BOND. The authors note limits: small size, COVID-era disruption and a duration that may be too short for a slowly progressing disease. They also state that the results do not contradict using benfotiamine for neuropathy caused by vitamin B1 deficiency, since participants were not selected for low B1.

Fraser’s trial has a similar caveat. BOND’s authors argue that few of its participants likely had confirmed neuropathy.

A 2026 meta-analysis pooled 13 randomized trials (834 participants) of any B vitamin, not benfotiamine alone. It found small improvements in some neuropathy scores and sural nerve function, no significant effect on pain by numeric or visual scales, and inconsistent motor nerve results. Benfotiamine alone generally failed to show robust nerve-conduction improvement, and combination regimens looked more promising, although most formal subgroup tests were not significant (Mandra et al., J Clin Med 2026). High-dose B6 in such combinations has its own neuropathy risk; see P5P. For other neuropathy supplements, see alpha-lipoic acid and vitamin B12.

Diabetic kidney disease

The two forms have separate trials, with no direct comparison between them:

  • Benfotiamine. In 82 people with type 2 diabetes and urinary albumin of 15–300 mg/24 h despite an ACE inhibitor or ARB, 900 mg/day for 12 weeks improved thiamine status (P under 0.001) but did not significantly reduce urinary albumin or the tubular damage marker KIM-1 (Alkhalaf et al., Diabetes Care 2010). Advanced glycation end products (AGEs) and markers of endothelial dysfunction and inflammation also did not change (Alkhalaf et al., PLoS One 2012).
  • Thiamine. In a pilot of 40 people with type 2 diabetes and microalbuminuria, thiamine 100 mg three times daily for 3 months reduced urinary albumin (median −17.7 mg/24 h from baseline; 30.1 vs 35.5 mg/24 h with placebo at 3 months; P under 0.01). Glucose control, lipids and blood pressure did not change (Rabbani et al., Diabetologia 2009). Being a pilot, this result needs confirmation in larger trials.

Vascular function

A 13-person study without a placebo group found that 1,050 mg/day of benfotiamine for 3 days prevented blood vessel dysfunction after a high-AGE meal (Stirban et al., Diabetes Care 2006). The same group’s larger follow-up, a placebo-controlled crossover in 31 people given 900 mg/day for 6 weeks, could not test this as intended. The test meal did not worsen vascular function even on placebo, and benfotiamine did not change the overall pattern (Stirban et al., Diabet Med 2013).

Alzheimer’s disease

The ODS reports that a 2001 Cochrane review of thiamine at 3 g/day found three trials with fewer than 20 patients each, too small for any conclusion. Benfotiamine data are as follows:

  • Phase IIa trial. People with amyloid-positive mild cognitive impairment or mild Alzheimer’s dementia took 600 mg/day (n = 34) or placebo (n = 36) for 12 months. The primary outcome, ADAS-Cog, worsened by 1.39 vs 3.26 points in the intention-to-treat analysis, which was not statistically significant (P = 0.162 by t-test; P = 0.071–0.137 by other methods). The abstract describes a 43% lower increase with P = 0.125, a P value the paper’s table gives for the per-protocol comparison. Global CDR worsening was 0.05 vs 0.22 points, or 77% lower (P = 0.034). Pre-specified brain glucose (FDG PET) regions did not differ. An exploratory pattern score differed at one year (P = 0.002), but its change over time did not (P = 0.638). The authors state that some significant secondary findings could be due to chance, because no correction was made for multiple comparisons (Gibson et al., J Alzheimers Dis 2020).
  • Case series. Five patients took 300 mg/day for 18 months, and MMSE scores rose by an average of 3.2 points. There was no control group, so this cannot show that benfotiamine caused the change (Pan et al., Neurosci Bull 2016).
  • BenfoTeam. A phase II, 72-week placebo-controlled trial planned for 406 people with early Alzheimer’s disease, with 600 or 1,200 mg/day carried forward depending on tolerability (Feldman et al., PLoS One 2024). The registry lists it as active and not recruiting, with completion estimated for December 2027 (NCT06223360). We found no published efficacy results.

Whether benfotiamine slows Alzheimer’s disease in people is unknown.

Alcohol use

A three-arm, 8-week trial of benfotiamine, benfotiamine with B6 and B12, and placebo reported improved vibration perception, motor function and overall score in 84 outpatients with severe alcoholic polyneuropathy (Woelk et al., Alcohol Alcohol 1998). In a 24-week trial of 120 actively drinking adults, 600 mg/day was well tolerated. Drinking fell in both groups, and a greater reduction appeared only in a subgroup of 21 women who completed the study, with 58% overall completion (Manzardo et al., Drug Alcohol Depend 2013). Neither trial tested benfotiamine as a treatment for Wernicke encephalopathy.

Exercise and muscle

Thiamine’s role in energy metabolism invites performance claims, but the direct evidence is thin and does not show a benefit:

  • Thiamine derivatives in people. In a double-blind crossover in 14 subjects, 1 g/day of thiamine tetrahydrofurfuryl disulfide (not benfotiamine) for 4 days did not change peak oxygen uptake, lactate threshold or 2,000-m cycling time (Webster et al., Eur J Appl Physiol 1997).
  • Benfotiamine in mice. Supplementation raised muscle thiamine in endurance-trained mice but did not lengthen exhaustive exercise (Gonçalves et al., J Nutr Metab 2024).

We found no controlled human trial of benfotiamine for strength, muscle mass or athletic performance.

Heart failure (thiamine)

The ODS describes a meta-analysis of two small placebo-controlled trials in which thiamine improved left ventricular ejection fraction, with clinical significance not assessed. A later systematic review considered the thiamine studies too small to appraise clinical outcomes (Hopper et al., J Card Fail 2020).

Side effects and risks

Injected thiamine: anaphylaxis

The label warns that serious hypersensitivity and anaphylactic reactions can occur, especially after repeated administration, and that deaths have resulted from IV or IM thiamine. History of sensitivity to thiamine or any ingredient is a contraindication. Other reported reactions include warmth, itching, hives, weakness, sweating, nausea, throat tightness, angioedema, cyanosis and pulmonary edema, plus tenderness at IM sites. The label calls for a skin test in patients with suspected drug allergy or a prior reaction, and for readiness to treat anaphylaxis regardless (FDA label).

How rare is it? Published estimates suggest very low rates, though they are imprecise:

Source Exposure Reactions
Wrenn et al., Ann Emerg Med 1989 989 consecutive patients; 1,070 doses of 100 mg IV thiamine 12 reactions (1.1%): 11 transient local irritation, 1 generalized itching; none anaphylaxis
Thomson et al., Alcohol Alcohol 2019 Pabrinex, a UK thiamine-containing injectable; estimated 5.4–6.65 million patient-days from sales data 10 anaphylactic reactions; authors judged the risk low and the risk-benefit ratio favorable

Sales data only approximate the doses given, so the true rate is uncertain. The EFNS guideline rates thiamine’s overall safety as very good (Galvin et al. 2010). A case report describes a woman who had anaphylaxis after her fourth monthly IM injection yet tolerated blinded oral thiamine, suggesting the route can matter (Aurich et al., Iran J Allergy Asthma Immunol 2018).

The label also warns about aluminum, which can reach toxic levels with prolonged parenteral use when kidney function is impaired. Premature infants are at particular risk. The product contains chlorobutanol, a chloral derivative, as a preservative. Thiamine should be used in pregnancy only if clearly needed.

Oral thiamine

Neither the US Food and Nutrition Board nor Europe’s Scientific Committee on Food set an upper limit, given the lack of reported harm, the sharp fall in absorption above 5 mg and urinary excretion of the excess. The European committee noted no evidence of toxicity at oral intakes up to 500 mg/day for one month (EFSA 2026). The US board cautioned that excessive intakes could still have adverse effects (NIH ODS).

Benfotiamine

Reported trial safety has been reassuring in the short and medium term, but long-term toxicology is largely missing. These are not contradictory, since trials are small and were not designed to find rare or delayed harm.

Source Dose and length Safety finding
Sheng et al. 2021 150–1,200 mg single doses; up to 600 mg twice daily for about a week; healthy adults Adverse events similar to placebo; isolated ALT rises and urinary findings
Gibson et al. 2020 600 mg/day for 12 months No related adverse events reported; none withdrew from benfotiamine because of adverse effects
BOND 2026 600 mg/day for 12 months 229 treatment-emergent events vs 140 on placebo, with five benfotiamine participants having considerably more; serious events in 21.4% vs 17.2% of participants, none rated drug-related

The EFSA opinion. EFSA reviewed benfotiamine as a novel food for supplements at up to 300 mg/day, and adopted its opinion in August 2026. The panel concluded that safety “cannot be established” under the proposed conditions. Its stated reasons were insufficient characterization of the ingredient (including possible nanoparticles), lack of information on metabolic fate, bioaccumulation and long-term effects, and limits in the toxicology package. The applicant provided no repeated-dose or human safety studies for this product, and the panel noted there is no history of safe use as a food (EFSA 2026). This is a finding of inadequate data rather than evidence of a specific harm. EFSA’s 2008 panel had reached a similar conclusion.

The EFSA applicant itself excluded people under 16 and pregnant and lactating women, for lack of safety data.

Drugs that can lower thiamine

The ODS says thiamine is not known to interact with medications, but some medications may lower thiamine:

  • Furosemide. Research links it to urinary thiamine loss. Whether supplements prevent deficiency in users of loop diuretics has not been determined.
  • Fluorouracil. Cases of beriberi and Wernicke encephalopathy have been reported during this chemotherapy.
  • Metformin. In a lab screen of drug inhibitors, metformin was among the oral drugs predicted to reach gut concentrations that could inhibit the thiamine transporter ThTR-2 (Vora et al., Am J Clin Nutr 2020). In US adverse event reports from 2004 to 2024, the most frequently reported agents among 1,046 thiamine deficiency cases were furosemide, metformin, fedratinib, metronidazole and fluorouracil (Du et al., JPEN 2026). Such reports reflect use patterns and reporting habits, and cannot prove causation. Metformin’s better-established vitamin effect is on vitamin B12.
  • United States. Thiamine is sold as a dietary supplement and, separately, as a prescription injection. The ODS lists benfotiamine as used in some supplements. Searches of Drugs@FDA and DailyMed in November 2026 returned no benfotiamine product.
  • European Union. According to the EFSA applicant, benfotiamine medicines have been authorized in Germany since 1998 and in Austria since 2005, for neurological diseases, neuropathy and back pain. EFSA’s 2026 opinion addresses food supplement use, not those medicines.
  • Anti-doping. Neither thiamine nor benfotiamine is named on the WADA 2026 Prohibited List.

For related B vitamins, see niacin, vitamin B12 and P5P.

Key takeaways

  • Two forms, two evidence bases. Thiamine is an essential vitamin with an FDA-labeled injection. Benfotiamine is a synthetic prodrug, and its data should not be assumed to apply to thiamine or the reverse.
  • Deficiency is a medical emergency when it reaches the brain. Wernicke encephalopathy can be fatal or leave lasting memory damage. Alcohol use disorder, bariatric surgery and prolonged vomiting or rapid weight loss, including on GLP-1 drugs, raise the risk.
  • The best parenteral dose is unproven. The label, the guideline and the trials differ. A 2022 randomized study found no clear benefit of higher doses over intermediate or lower ones.
  • Higher blood levels have not meant better outcomes. Benfotiamine raises blood thiamine strongly, yet 12- and 24-month neuropathy trials and a 12-week kidney trial found no significant benefit.
  • Alzheimer’s data are preliminary. A 70-person phase IIa trial missed its primary endpoint with a positive secondary signal. A 406-person trial is ongoing.
  • Safety differs by form. Rare, sometimes fatal anaphylaxis is linked to injected thiamine. Benfotiamine was well tolerated in trials, but EFSA in 2026 could not establish its safety as a novel food because of data gaps.

Sources

  1. National Institutes of Health Office of Dietary Supplements. Thiamin: fact sheet for health professionals. Updated February 9, 2023. NIH ODS.
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  8. Moraes RCM, Singulani MP, Gonçalves AC, et al. Oral benfotiamine reverts cognitive deficit and increase thiamine diphosphate levels in the brain of a rat model of neurodegeneration. Exp Gerontol. 2020;141:111097. PubMed.
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