Table 1.

An overview of the effects of benfotiamine in the treatment of diabetic complications, neurodegenerative diseases and inflammatory complications.

Disease	Proposed mechanisms of action	Clinical trials	In vivo models	In vitro models
Diabetes	Inhibition of hexosamine pathway, AGE formation, DAG –PKC pathway (Hammes et al., 2003) Inhibition of NF-κB (Hammes et al., 2003)	Randomized, double-blind, placebo controlled study in progress, to evaluate benfotiamine effects on diabetic sensorimotor polyneuropathy (Bonhof et al., 2022) Enhanced thiamine levels in a small randomized, double-blind, placebo-controlled trial, but without the effect on urinary albumin excretion and tubular damage marker kidney injury molecule-1 (Alkhalaf et al., 2010) No changes in plasma or urinary AGEs, plasma markers of inflammation and endothelial dysfunction after 12 weeks treatment in a randomized, placebo-controlled study (Alkhalaf et al., 2012) No effect on peripheral nerve function or soluble markers of inflammation in patients with type I diabetes in a small, randomized, placebo-controlled study (Fraser et al., 2012)	Inhibition of three important biochemical pathways (hexosamine pathway, AGE formation, DAG –PKC pathway) implicated in pathogenesis of diabetes and inhibition of NF-κB in retinas of streptozotocin induced diabetic rats (Hammes et al., 2003) Decrease in inflammatory and neuropathic pain in a rat model of diabetes (Sanchez-Ramirez et al., 2006) Reduction in cerebral oxidative stress in diabetic mice (Wu and Ren, 2006) Increase in motor nerve conduction velocity, decrease in AGEs, inhibition of glycoxidation products in diabetic rats (Stracke et al., 2001)	Inhibition of three important biochemical pathways (hexosamine pathway, AGE formation, DAG –PKC pathway) implicated in pathogenesis of diabetes and inhibition of NF-κB in aortic endothelial cells (Hammes et al., 2003)
Alzheimerˈs disease	Decreased GSK-3 activity (Pan et al., 2010; Moraes et al., 2020) Suppression of ERK1/2 activity (Moraes et al., 2020) Antioxidative and anti-inflammatory activity, reduced mitochondrial dysfunction, activation of Nrf2 (Tapias et al., 2018)	Improved cognitive ability in small, uncontrolled clinical trial performed on 5 patients (Pan et al., 2016) Improved cognitive ability in small, double-blind, placebo controlled study (Gibson et al., 2020)	Improved cognitive function in APP/presenilin 1 transgenic mice Reduced amyloid plaque numbers and tau phosphorylation levels (Pan et al., 2010) Increased lifespan, improved behavioral deficits, decreased neurofibrillary tangles, prevented motor neuron death (Tapias et al., 2018)	Decreased GSK-3 activity Suppression of β-amyloid production in HEK cells (Sun et al., 2012)
Alcoholism	Increased thiamine levels Anti-oxidative effects	Improved alcoholic polyneuropathy in a small, randomized, placebo-controlled study (Woelk et al., 1998) Reduced alcohol consumption in women in a small, double-blind, randomized, placebo-controlled study (Manzardo et al., 2013)	Reduced hepatic alcohol concentrations and oxidative stress markers after ethanol gavage in rats (Portari et al., 2016)