Dr. Richard Mann

Research

The scientific literature

A curated reference library on benfotiamine, vitamin B1, and the research areas where they have been studied.

Reference library

External literature on benfotiamine, vitamin B1, and related research.

ByDr. Richard H. Mann, DPM, DABPS, ret.Reviewed May 21, 2026 by Dr. Richard H. Mann

Peer-reviewed studies, reviews, and clinical trials referenced across this site. Each citation links to the source where available.

Benfotiamine and Polyneuropathy

  1. Exp Clin Endocrinol Diabetes · 2008 · 116(10):600-5

    Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study

    Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG

    A double blind, placebo-controlled, phase-III study of 165 patients with symmetrical, distal diabetic polyneuropathy. After 6 weeks, the NSS (Neuropathy Symptom Score) differed significantly between benfotiamine (600mg/day or 300mg/day) and placebo groups (p=0.033 in PP population). Treatment was well tolerated; improvement most pronounced at higher doses.

    View sourcePMID: 18473286

  2. Int J Clin Pharmacol Ther · 2005 · 43(2):71-7

    Benfotiamine in the treatment of diabetic polyneuropathy: a three-week randomized, controlled pilot study (BEDIP Study)

    Haupt E, Ledermann H, Köpcke W

    40 inpatients with diabetes and polyneuropathy received either 400mg benfotiamine daily or placebo for 3 weeks. Statistically significant improvement (p=0.0287) in neuropathy score in active group. Most pronounced effect on pain (p=0.0414).

    View sourcePMID: 15726875

  3. Arzneimittelforschung · 1999 · 49(3):220-4

    Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy

    Winkler G, Pál B, Nagybéganyi E, Ory I, Porochnavec M, Kempler P

    36 patients in three groups; greatest improvement seen in high-dose group (320mg/day benfotiamine).

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  4. Alcohol Alcohol · 1998 · 33(6):631-8

    Benfotiamine in the treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP study)

    Woelk H, Lehrl S, Bitsch R, Köpcke W

    Three-armed RCT in 84 outpatients with severe alcoholic polyneuropathy. Benfotiamine produced significant improvement in vibration perception, motor function, and overall score. No therapy-specific adverse effects.

    View sourcePMID: 9872352

  5. Exp Clin Endocrinol Diabetes · 1996 · 104(4):311-6

    A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy

    Stracke H, Lindemann A, Federlin K

    12-week double-blind RCT in 24 diabetic patients. Significant improvement (p=0.006) of nerve conduction velocity in peroneal nerve.

    View source

  6. Int J Clin Pharmacol Ther · 1996 · 34(2):47-50

    Pharmacokinetics of thiamine derivatives, especially benfotiamine

    Loew D

    Pharmacokinetic comparison showing benfotiamine reaches plasma and tissue thiamine concentrations several-fold higher than equivalent oral thiamine doses, owing to passive diffusion across the gut wall.

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Benfotiamine, Thiamine and Diabetic Complications

  1. Int J Clin Pract · 2011 · 65(6):684-90

    Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

    Page GL, Laight D, Cummings MH

    View source

  2. Pharmacol Res · 2010 · 61(6):482-8

    The multifaceted therapeutic potential of benfotiamine

    Balakumar P, Rohilla A, Krishan P, Solairaj P, Thangathirupathi A

    Comprehensive review of benfotiamine's anti-AGE properties and research into diabetic neuropathy, nephropathy, and retinopathy.

    View source

  3. Diabetologia · 2007 · 50(10):2164-70

    High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease

    Thornalley PJ, Babaei-Jadidi R, Al Ali H

    Plasma thiamine concentration was decreased 76% in type 1 and 75% in type 2 diabetic patients. Renal clearance of thiamine increased 24-fold (type 1) and 16-fold (type 2).

    View source

  4. Diabetes · 2005 · 54(6):1615-25

    The pathobiology of diabetic complications: a unifying mechanism

    Brownlee M

    View source

  5. Curr Diabetes Rev · 2005 · 1(3):287-98

    The potential role of thiamine (vitamin B1) in diabetic complications

    Thornalley PJ

    Argues for thiamine therapy in preventing diabetic complications via the reductive pentose phosphate pathway.

    View source

  6. Nat Med · 2003 · 9(3):294-9

    Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy

    Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M

    Mechanistic study showing benfotiamine activates transketolase, redirecting metabolites away from the polyol, hexosamine, and AGE pathways that drive hyperglycemic tissue damage.

    View sourcePMID: 12592403

Metformin and Vitamin B1 and B12 Deficiency

  1. Mol Pharm · 2015 · 12(12):4301-10

    Metformin is a substrate and inhibitor of the human thiamine transporter, THTR-2 (SLC19A3)

    Liang X

    Demonstrates metformin transports via and inhibits thiamine transporter THTR-2 in the small intestine. Implications for thiamine deficiency in metformin-treated diabetics.

    View source

  2. BMJ · 2010 · 340:c2181

    Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial

    de Jager J

    Metformin treatment associated with -19% decrease in vitamin B-12 concentration; long-term metformin use increases risk of B-12 deficiency.

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Benfotiamine, Thiamine and Alzheimer's Disease

  1. Mol Cell Neurosci · 2013 · 55:17-25

    Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes

    Gibson GE, Hirsch JA, Cirio RT, Jordan BD, Fonzetti P, Elder J

    View source

  2. Brain · 2010 · 133(Pt 5):1342-51

    Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice

    Pan X, Gong N, Zhao J, Yu Z, Gu F, Chen J, Sun X, Zhao L, Yu M, Xu Z, Dong W, Qin Y, Fei G, Zhong C, Xu TL

    Mouse Alzheimer's model: benfotiamine dose-dependently enhanced spatial memory and reduced amyloid plaque and phospho-tau. Foundational preclinical evidence for benfotiamine's CNS effects.

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  3. Metab Brain Dis · 1996 · 11(1)

    Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer's disease

    Heroux M

    Significantly reduced activities of thiamine phosphate dephosphorylating enzymes and thiamine-dependent enzymes in AD brain tissue.

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Thiamine Deficiency

  1. J Lab Clin Med · 1999 · 134(3):238-43

    Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers

    Rieck J, Halkin H, Almog S

    View source

  2. Am J Clin Nutr · 1980 · 33(12):2750-61

    Mechanisms of thiamin deficiency in chronic alcoholism

    Hoyumpa AM Jr

    Reviews ethanol inhibition of intestinal thiamine transport via reduced Na-K ATPase activity.

    View source

  3. Arch Neurol · 1976 · 33(12):836-41

    Axonal degeneration in beriberi neuropathy

    Takahashi K, Nakamura H

    View source

Mitochondrial Dysfunction and Polyneuropathy

  1. Nat Rev Neurol · 2014 · 10:326-336

    Mitotoxicity in distal symmetrical sensory peripheral neuropathies

    Bennett GJ, Doyle T, Salvemini D

    Reviews how mitochondrial injury from chemotherapy, HIV proteins, and hyperglycemia leads to chronic neuronal energy deficit and distal axonal degeneration.

    View source

  2. Dev Med Child Neurol · 2012 · 54(5):407-14

    Peripheral neuropathy associated with mitochondrial disease in children

    Menezes MP, Ouvrier RA

    View source

  3. Ann Neurol · 2011 · 69(1):100-10

    Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy

    Lehmann HC, Chen W, Borzan J, Mankowski JL, Höke A

    View source

  4. Neuroscientist · 2008 · 14(1):12-8

    Mitochondrial dynamics and peripheral neuropathy

    Baloh RH

    View source

  5. Pain · 2006 · 122(3):245-57

    Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: evidence for mitochondrial dysfunction

    Flatters SJ, Bennett GJ

    Paclitaxel produces atypical (swollen and vacuolated) mitochondria in both C-fibres and myelinated axons in painful peripheral neuropathy.

    View source

  6. J Peripher Nerv Syst · 2003 · 8(4):227-35

    Mechanism of mitochondrial dysfunction in diabetic sensory neuropathy

    Fernyhough P, Huang TJ, Verkhratsky A

    Insulin and NT-3 modulate mitochondrial membrane potential in adult sensory neurons via PI 3 kinase pathway.

    View source

Peripheral Neuropathy in Older Patients

  1. J Am Board Fam Pract · 2004 · 17(5):309-18

    The prevalence, predictors, and consequences of peripheral sensory neuropathy in older patients

    Mold JW, Vesely SK, Keyl BA, Schenk JB, Roberts M

    Prevalence of bilateral sensory deficits rose from 26% (65-74 yrs) to 54% (85+). Only 40% of cases had a known cause.

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Cobalamin

  1. J Clin Oncol · 2017 · 35(30):3440-3448

    Long-term, supplemental, one-carbon metabolism-related vitamin B use in relation to lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort

    Brasky TM, White E, Chen CL

    High-dose B6 and B12 supplementation linked to almost 2-fold increase in lung cancer risk in men, especially smokers.

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  2. QJM · 2009 · 102(1):17-28

    An update on cobalamin deficiency in adults

    Dali-Youcef N, Andrès E

    View source

  3. Blood Rev · 2007 · 21(3):113-30

    Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment

    Solomon LR

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Polyneuropathy and Prediabetes

  1. Diabetes Care · 2015 · 38:793-800

    Peripheral neuropathy and nerve dysfunction in individuals at high risk for type 2 diabetes: the PROMISE cohort

    Lee CC, Perkins BA

    Prevalence of peripheral neuropathy: 29% in normal glycemia, 49% in prediabetes, 50% in new-onset diabetes (p<0.001 for trend). Prediabetes was associated with similar risks of peripheral neuropathy and severity of nerve dysfunction as new-onset diabetes.

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