In plain terms: Benfotiamine shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Benfotiamine
The evidence as the record states it
Haupt et al. (Int J Clin Pharmacol Ther, 2005; PMID 15726875, BEDIP): 3-week randomized placebo-controlled pilot, 40 inpatients, 400 mg/day; neuropathy score improved against placebo (P=0.0287), pain fell (P=0.0414), the tuning-fork test did not change. Stracke et al. (Exp Clin Endocrinol Diabetes, 2008; PMID 18473286, BENDIP): 6-week randomized placebo-controlled trial, 165 randomized, 300 or 600 mg/day; the Neuropathy Symptom Score differed in the per-protocol analysis (P=0.033) and narrowly missed in the intention-to-treat analysis (P=0.055); the Total Symptom Score did not differ. Fraser et al. (Diabetes Care, 2012; PMID 22446172): 24-month randomized placebo-controlled trial, 67 adults with type 1 diabetes, 300 mg/day; no difference in nerve function or inflammatory markers. Ziegler et al. (BMJ Open Diabetes Research and Care, 2026; PMID 41571333): 12-month randomized placebo-controlled trial in type 2 diabetes, 300 mg twice daily; corneal nerve fiber length (primary) and every secondary measure did not differ. Stirban et al. (Diabet Med, 2013; PMID 23701274): 6-week crossover trial on postprandial vascular function, null. Grade C: the two short trials report symptom-score gains, the two trials of a year or longer find no effect on nerve measures.
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.