Benefits
Nerve symptom and nerve function scores
In adults with diabetes and nerve symptoms, 400 mg a day for 3 weeks (40 people) and 300 or 600 mg a day for 6 weeks (165 people) improved nerve symptom scores versus placebo, the 6-week result in the per-protocol analysis only. Trials of 12 months (57 people) and 24 months (67 people) found no significant effect on nerve measures.
Blood thiamine levels compared with thiamine hydrochloride
In healthy volunteers, oral benfotiamine gave about 11 times the plasma thiamine exposure of thiamine hydrochloride and about twice the red blood cell thiamine diphosphate, the active coenzyme form. Long-term trials also showed large rises in blood thiamine, even where nerve outcomes did not change.
Mechanism of action
Transketolase activation
In diabetic animals, benfotiamine activated transketolase, a thiamine-dependent enzyme that shifts glucose breakdown products into the pentose phosphate pathway. This reduced flux through three damaging pathways (hexosamine, AGE formation and protein kinase C), along with NF-kB activation in the retina. This has not been shown in human trials.
Absorption after dephosphorylation in the gut
Benfotiamine is practically insoluble in water, organic solvents and oil. Lab researchers propose that intestinal alkaline phosphatases remove its phosphate group before it is absorbed, after which it is turned into thiamine. This sets it apart from lipid-soluble disulfides such as allithiamine, sulbutiamine and fursultiamine.
Mainly peripheral rather than brain thiamine
In mice, a single oral dose or 14 days of benfotiamine raised thiamine in blood and liver but not in the brain, and it did not raise thiamine in cultured nerve cells. The authors concluded that it likely acts mainly in peripheral tissues.
Clinical trials
Randomized, double-blind, placebo-controlled pilot study at two centers; two 50 mg tablets four times daily. The abstract does not name the product brand or the funding source. (Haupt et al. 2005, Int J Clin Pharmacol Ther)
40 hospital inpatients with type 1 or type 2 diabetes and nerve damage (polyneuropathy) present for 2 years or less.
The neuropathy score improved more with benfotiamine than with placebo (p = 0.0287), and pain fell more (p = 0.0414). Vibration sense on the tuning fork test did not change significantly, and patient-rated improvement was borderline (p = 0.052). No side effects were attributed to treatment, and HbA1 and blood sugar profiles did not change significantly.
Randomized, double-blind, placebo-controlled multicenter phase 3 trial with three arms. The abstract does not name the product brand or the funding source. (Stracke et al. 2008, Exp Clin Endocrinol Diabetes)
165 adults with symmetric distal nerve damage from diabetes randomized to benfotiamine 600 mg/day, 300 mg/day or placebo for 6 weeks; 133 were in the intention-to-treat analysis and 124 in the per-protocol analysis.
The primary Neuropathy Symptom Score differed between groups in the per-protocol analysis (p = 0.033) but only borderline in the intention-to-treat analysis (p = 0.055). The Total Symptom Score showed no significant difference. Gains were larger at the higher dose, and pain responded best. Treatment was well tolerated.
Randomized, double-blind, placebo-controlled phase 2 trial sponsored by Wörwag Pharma, a benfotiamine maker; the product was its Milgamma mono 300 versus matching placebo. Three authors were Wörwag employees and two received honoraria from it. (Ziegler et al. 2026, BMJ Open Diabetes Res Care)
57 adults with type 2 diabetes and mild to moderate symptomatic nerve damage, randomized 1:1 to benfotiamine 300 mg twice daily or placebo for 12 months.
The primary outcome, change in corneal nerve fiber length, did not differ between groups. Most other structural, nerve conduction, clinical and quality of life measures were also similar; the Neuropathy Symptom Score showed a nonsignificant trend (p = 0.098). All six thiamine measures rose with benfotiamine. Adverse event rates did not differ in a relevant way.
Randomized, double-blind, placebo-controlled trial. (Fraser et al. 2012, Diabetes Care)
67 adults with type 1 diabetes randomized to benfotiamine 300 mg/day or placebo for 24 months; 59 completed.
Whole blood thiamine and thiamine diphosphate rose markedly with benfotiamine (P < 0.001), but changes in peripheral nerve function and soluble inflammatory markers did not differ significantly from placebo.
Randomized pharmacokinetic study with single and multiple benfotiamine doses. (Xie et al. 2014, J Clin Pharmacol)
Healthy Chinese volunteers; group size and doses are not given in the abstract.
Relative to thiamine hydrochloride, benfotiamine gave about 1147% bioavailability for plasma thiamine and about 196% for red blood cell thiamine diphosphate, with faster and greater absorption. Conversion produced hippuric acid, which did not build up after repeated doses.
Two randomized, double-blind, placebo-controlled phase 1 trials. Two authors held shares in Shanghai Rixin Biotech, a company developing Alzheimer's drugs. (Sheng et al. 2021, Drug Des Devel Ther)
Healthy adults given single doses of 150 to 1,200 mg or repeated doses of 150, 300 or 600 mg, with placebo in each cohort.
Adverse events were similar in frequency and severity to placebo. The most common drug-related events were raised ALT and white blood cells in urine. Thiamine and thiamine diphosphate built up moderately with repeated dosing.