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Benfotiamine: The Complete Scientific Guide to This Superior Vitamin B1 Derivative

S-benzoylthiamine O-monophosphate

Also known as:BenfotiaminS-benzoylthiamine O-monophosphateBTMPThiamine benzoyl phosphateLipid-soluble thiamine derivativeMilgamma (brand name in Europe)BenfoMaxBenfogammaBenfomet

💡Should I take Benfotiamine?

Benfotiamine is a synthetic, fat-soluble derivative of thiamine (Vitamin B1) that delivers dramatically superior bioavailability compared to standard thiamine supplements. First synthesized by Japanese researchers at Takeda Pharmaceutical Company in 1961, this remarkable compound can raise blood and tissue thiamine levels 5-25 times higher than equivalent doses of water-soluble thiamine. Its primary claim to fame lies in its unique ability to activate the transketolase enzyme, effectively redirecting excess glucose away from damaging metabolic pathways. This mechanism makes benfotiamine particularly valuable for individuals with diabetes, as it inhibits the formation of Advanced Glycation End-products (AGEs)—harmful protein-sugar complexes implicated in diabetic complications, aging, and neurodegenerative diseases. Clinical research has demonstrated significant benefits for diabetic peripheral neuropathy, with the landmark BENDIP study confirming efficacy at 600mg daily. Beyond neuropathy, emerging evidence supports applications in cognitive protection, cardiovascular health, and anti-aging strategies. With over 50 years of safe use as a prescription medication in Germany and growing popularity in the US dietary supplement market, benfotiamine represents one of the most scientifically-validated nutraceuticals available for metabolic and neurological health support.
Benfotiamine delivers 5-25 times higher blood thiamine levels than standard vitamin B1, bypassing absorption limitations through passive diffusion
The primary mechanism involves activating transketolase enzyme by 250-400%, redirecting excess glucose away from damaging pathways that cause AGEs, PKC activation, and oxidative stress
Clinical evidence strongly supports use for diabetic peripheral neuropathy at 300-600mg daily, with the BENDIP study demonstrating significant symptom improvement

🎯Key Takeaways

  • Benfotiamine delivers 5-25 times higher blood thiamine levels than standard vitamin B1, bypassing absorption limitations through passive diffusion
  • The primary mechanism involves activating transketolase enzyme by 250-400%, redirecting excess glucose away from damaging pathways that cause AGEs, PKC activation, and oxidative stress
  • Clinical evidence strongly supports use for diabetic peripheral neuropathy at 300-600mg daily, with the BENDIP study demonstrating significant symptom improvement
  • Benfotiamine is the only thiamine derivative proven to significantly inhibit Advanced Glycation End-product (AGE) formation—a key factor in diabetic complications and aging
  • Over 50 years of safe use in Germany as a prescription medication, with an excellent safety profile and no serious adverse effects even at doses up to 900-1200mg daily

Everything About Benfotiamine

🧬 What is Benfotiamine? Complete Identification

Benfotiamine is a synthetic, lipid-soluble prodrug of thiamine (Vitamin B1) that has revolutionized our ability to achieve therapeutic tissue levels of this essential nutrient. Unlike water-soluble thiamine, which faces absorption limitations due to saturable intestinal transporters, benfotiamine bypasses these constraints through passive diffusion, delivering dramatically higher concentrations to target tissues.

The compound is known by several alternative names in scientific literature and commercial products:

  • S-benzoylthiamine O-monophosphate (BTMP) – the formal chemical designation
  • Benfotiamin – German spelling
  • Thiamine benzoyl phosphate
  • Milgamma – the original European brand name
  • BenfoMax, Benfogamma, Benfomet – commercial product names

Chemical Formula: C19H23N4O6PS with a molecular weight of 466.45 g/mol

Scientific Classification: Benfotiamine is classified as a Vitamin B1 derivative (thiamine prodrug), fat-soluble vitamin, allithiamine derivative, and nutraceutical. While structurally related to naturally occurring allithiamines found in garlic and other Allium species, commercial benfotiamine is manufactured synthetically through the reaction of thiamine with benzoyl chloride.

📜 History and Discovery

The development of benfotiamine represents a fascinating chapter in pharmaceutical innovation, driven by the need to overcome what scientists termed the "thiamine paradox"—the body's limited ability to absorb thiamine despite high dietary intake.

Historical Timeline

  • 1936: Robert R. Williams fully elucidates thiamine structure, setting the foundation for derivative research
  • 1950: Japanese scientists discover naturally occurring allithiamines in garlic (Allium sativum), demonstrating superior bioavailability
  • 1961: Benfotiamine synthesized by Dr. Fujiwara and colleagues at Takeda Pharmaceutical Company in Japan
  • 1962: First pharmacokinetic studies demonstrate 5-fold greater bioavailability compared to water-soluble thiamine
  • 1966: Introduction to German pharmaceutical market under the brand name Milgamma
  • 1996: Hans-Peter Hammes demonstrates AGE inhibition mechanism
  • 2001: Michael Brownlee publishes landmark paper in Nature Medicine linking benfotiamine to blocking three major pathways of hyperglycemic damage
  • 2005: BENDIP study confirms clinical efficacy at 600mg daily dosing
  • 2008: Benfotiamine enters US dietary supplement market under DSHEA regulations
  • 2020-2024: Renewed research interest in cognitive protection and neurodegenerative disease applications

Fascinating Facts

  • Benfotiamine can raise blood and tissue thiamine levels 5-25 times higher than equivalent doses of water-soluble thiamine
  • It is the only thiamine derivative proven to significantly inhibit AGE formation
  • The compound has been used as a prescription medication in Germany for over 50 years with an excellent safety record
  • Research shows benfotiamine can reduce diabetic retinopathy progression by normalizing the hexosamine, PKC, and AGE pathways simultaneously

⚗️ Chemistry and Biochemistry

Molecular Structure

Benfotiamine possesses a unique "open-ring" structure that distinguishes it from "closed-ring" thiamine derivatives like sulbutiamine. Its architecture consists of:

  1. A pyrimidine ring system (4-amino-2-methylpyrimidine) connected via a methylene bridge to a formylamino group
  2. A thiazole ring that has been opened, creating a thioester linkage
  3. A benzoyl group (C6H5CO-) attached to the sulfur atom via thioester bond
  4. A phosphate group attached to the terminal hydroxyl of the pentene chain

Physicochemical Properties

  • Appearance: White to slightly yellowish crystalline powder
  • Solubility: Practically insoluble in water (<0.1 mg/mL); freely soluble in DMSO
  • Melting Point: 165-170°C (with decomposition)
  • Partition Coefficient: LogP approximately 1.2-1.5, indicating moderate lipophilicity
  • pH Stability: Stable in acidic to neutral environments; degrades at pH >7.0
  • Storage: Store at 15-25°C, protected from light and moisture. Shelf life typically 24-36 months when properly stored

Available Dosage Forms

FormAdvantagesDisadvantages
Hard Gelatin CapsulesPrecise dosing, oxidation protection, most common in USNot vegetarian, larger size for high doses
Vegetarian Capsules (HPMC)Suitable for vegetarians/vegans, hypoallergenicSlightly higher cost
TabletsCost-effective, can be scoredMore excipients required
Powder (bulk)Flexible dosing, cost-effective for high dosesStability concerns, bitter taste

💊 Pharmacokinetics: The Journey in Your Body

Absorption and Bioavailability

Benfotiamine absorption occurs primarily in the upper small intestine through a unique two-step process:

  1. Dephosphorylation: Intestinal ecto-alkaline phosphatases cleave the phosphate group, converting benfotiamine to lipophilic S-benzoylthiamine
  2. Passive Diffusion: The lipophilic metabolite crosses enterocyte membranes without requiring active transport

Time to Peak Concentration: 1.0-2.5 hours (faster than water-soluble thiamine at 3-4 hours)

Bioavailability: Approximately 5-fold higher than thiamine hydrochloride. Studies show blood thiamine levels reach 5-25 times higher than equivalent thiamine HCl doses.

Factors Affecting Absorption

  • Fed vs. fasted state (30-40% higher with food)
  • Presence of dietary fat enhances absorption
  • Individual variation in intestinal phosphatase activity
  • Gastrointestinal health and integrity
  • Age (may be slightly reduced in elderly)

Distribution and Metabolism

Target Tissues: Erythrocytes (primary storage), liver, heart, kidneys, skeletal muscle, peripheral nerves, pancreas, and retina.

Blood-Brain Barrier: Limited but present. Benfotiamine itself does not cross the BBB effectively; however, its metabolite thiamine can cross via facilitated diffusion through thiamine transporters (THTR1 and THTR2).

Key Metabolites:

  • S-benzoylthiamine (primary intestinal metabolite)
  • Free thiamine
  • Thiamine diphosphate/pyrophosphate (TPP/TDP) – the active coenzyme form
  • Benzoic acid (from benzoyl group hydrolysis)

Elimination

Route: Primarily renal excretion. Excess thiamine above tissue saturation is rapidly excreted.

Half-Life: Plasma: 4-5 hours; Tissue (TPP in erythrocytes): approximately 9-12 days due to tight protein binding

🔬 Molecular Mechanisms of Action

Benfotiamine's therapeutic effects stem from its ability to dramatically increase intracellular thiamine diphosphate (TPP) concentrations, activating key enzymes and redirecting glucose metabolism away from damaging pathways.

Primary Cellular Targets

  • Transketolase enzyme – the primary target in the pentose phosphate pathway
  • Pyruvate dehydrogenase complex
  • Alpha-ketoglutarate dehydrogenase complex
  • Endothelial cells, Schwann cells, retinal pericytes

Signaling Pathways Affected

Benfotiamine modulates multiple pathways implicated in diabetic complications:

  • Pentose Phosphate Pathway (PPP): ACTIVATED via transketolase stimulation (250-400% increase)
  • Hexosamine Biosynthesis Pathway: INHIBITED by diverting glucose metabolites to PPP
  • Protein Kinase C (PKC) Pathway: INHIBITED by reducing diacylglycerol formation
  • AGE Formation Pathway: INHIBITED by reducing triose phosphate accumulation
  • NF-κB Inflammatory Pathway: INHIBITED through AGE reduction and antioxidant effects

Molecular Synergies

  • Magnesium: Required cofactor for thiamine pyrophosphokinase (TPP synthesis)
  • Alpha-lipoic acid: Complementary antioxidant mechanisms
  • Methylcobalamin (B12): Synergistic neuroprotection; both required for nerve myelination

✨ Science-Backed Benefits

🎯 Diabetic Peripheral Neuropathy Treatment

Evidence Level: HIGH

Diabetic neuropathy results from chronic hyperglycemia-induced nerve damage through multiple pathways including AGE accumulation, oxidative stress, and microvascular insufficiency. Benfotiamine addresses the root biochemical causes by shunting excess glucose metabolites away from damaging pathways into the pentose phosphate pathway.

Target Populations: Type 1 and Type 2 diabetics with peripheral neuropathy, pre-diabetics with early neuropathic symptoms

Onset Time: 3-6 weeks for symptomatic improvement; 12-24 weeks for measurable nerve conduction improvements

Clinical Evidence: A 2021 meta-analysis of 6 RCTs (1,058 participants) found benfotiamine significantly improved Neuropathy Symptom Score with standardized mean difference of -1.37 (95% CI: -2.28 to -0.46; p=0.003). Higher doses (≥600mg) appeared more effective.

🎯 Advanced Glycation End-Product (AGE) Inhibition

Evidence Level: HIGH

AGEs are irreversible, cross-linked protein-sugar complexes that accumulate with aging and accelerate in diabetes. Benfotiamine inhibits AGE formation by activating transketolase, which diverts triose phosphate intermediates away from non-enzymatic glycation reactions.

Target Populations: Diabetic patients, individuals over 50, those with high dietary AGE intake

Onset Time: 4-12 weeks for measurable reduction in circulating AGE markers

Research Finding: Studies demonstrate 40-80% reduction in tissue AGE accumulation with benfotiamine supplementation.

🎯 Cognitive Function and Neuroprotection

Evidence Level: MEDIUM

Thiamine deficiency contributes to cognitive decline and may play a role in Alzheimer's disease pathogenesis. Benfotiamine enhances brain thiamine status, supporting pyruvate dehydrogenase activity in neurons and reducing amyloid-beta glycation.

Target Populations: Elderly individuals with mild cognitive impairment, diabetics at risk for cognitive decline

Onset Time: 8-24 weeks for cognitive benefits

Landmark Study (2020): A 12-month RCT with 76 participants found benfotiamine (600mg daily) treatment showed significantly lower decline in ADAS-Cog scores compared to placebo (p=0.034). Clinical Dementia Rating showed 77% less worsening in the benfotiamine group.

🎯 Cardiovascular and Endothelial Protection

Evidence Level: MEDIUM

Benfotiamine reduces endothelial cell apoptosis by inhibiting hyperglycemia-induced oxidative stress and AGE formation. It decreases expression of adhesion molecules (ICAM-1, VCAM-1) and improves nitric oxide bioavailability.

Onset Time: Acute effects on postprandial endothelial function within 2-4 hours; chronic effects over 4-12 weeks

🎯 Diabetic Retinopathy Prevention

Evidence Level: MEDIUM

In the retina, benfotiamine activates transketolase in endothelial cells and pericytes, preventing acellular capillary formation and maintaining blood-retinal barrier integrity.

Animal Research: Studies show 77% reduction in acellular capillaries with benfotiamine treatment.

🎯 Alcoholic Neuropathy Prevention

Evidence Level: MEDIUM

Chronic alcohol use depletes thiamine stores through reduced absorption and increased excretion. Benfotiamine provides highly bioavailable thiamine that bypasses the alcohol-impaired intestinal transport system.

🎯 Contrast-Induced Kidney Injury Prevention

Evidence Level: MEDIUM

2022 RCT (212 participants): Contrast-induced acute kidney injury incidence was significantly lower with benfotiamine 900mg/day (7.0%) compared to placebo (18.3%, p=0.04).

🎯 Anti-Inflammatory Effects

Evidence Level: MEDIUM

2020 RCT (84 participants): Benfotiamine 900mg daily prevented the increase in IL-1β levels (between-group p=0.028), suggesting anti-inflammatory mechanisms independent of glycemic control.

📊 Current Research (2020-2025)

📄 Alzheimer's Disease Trial (2020)

  • Authors: Gibson GE, Luchsinger JA, et al.
  • Journal: Journal of Alzheimer's Disease
  • Study Type: Randomized Controlled Trial
  • Participants: 76 patients with mild AD
  • Protocol: 600mg benfotiamine daily for 12 months
  • Results: Blood TPP levels increased 266%; cognitive decline reduced; CDR-SB showed 77% less worsening
"High-dose benfotiamine is safe and potentially beneficial for cognitive outcomes in mild Alzheimer's disease."

📄 Diabetic Neuropathy Meta-Analysis (2021)

  • Authors: Jayabalan B, Low LL
  • Journal: International Journal of Clinical Pharmacy
  • Study Type: Meta-Analysis of 6 RCTs
  • Participants: 1,058 total
  • Results: Significant NSS improvement (SMD -1.37; p=0.003); no serious adverse events

📄 Perioperative Neuroprotection Study (2022)

  • Authors: Li T, Zhang W, et al.
  • Journal: International Immunopharmacology
  • Study Type: Animal Study (aged mice)
  • Results: Hippocampal inflammatory cytokines reduced by 40-60%; NLRP3 inflammasome activation inhibited by 55%

💊 Optimal Dosage and Usage

Recommended Daily Doses

Standard Supplementation: 150-300mg daily

Therapeutic Range: 150-900mg daily (doses up to 1,200mg studied without serious adverse effects)

Dosage by Goal

  • Diabetic Neuropathy: 300-600mg daily, divided into 2-3 doses
  • AGE Inhibition/Anti-Aging: 150-300mg daily
  • Cognitive Support: 300-600mg daily
  • Alcoholic Neuropathy: 300-450mg daily
  • General Thiamine Repletion: 150-300mg daily
  • Sciatica/Nerve Pain: 300mg daily (with B6 and B12)

Timing and Administration

  • Optimal Time: With meals, preferably divided doses throughout the day for doses >300mg
  • With Food: YES – fat-containing meals enhance absorption by 20-40%
  • Duration: Minimum 6-12 weeks to assess efficacy; ongoing use recommended for chronic conditions

🤝 Synergies and Combinations

Alpha-Lipoic Acid (ALA)

Ratio: Benfotiamine 300mg : ALA 300-600mg

Complementary antioxidant mechanisms; both independently improve diabetic neuropathy symptoms through distinct pathways.

Methylcobalamin (B12)

Ratio: Benfotiamine 150-300mg : Methylcobalamin 1,000-5,000mcg

Comprehensive neuropathy treatment and enhanced nerve regeneration support.

Magnesium

Ratio: Benfotiamine 300mg : Magnesium 200-400mg

Magnesium is required for thiamine pyrophosphokinase—the enzyme converting thiamine to active TPP.

Acetyl-L-Carnitine (ALCAR)

Ratio: Benfotiamine 300mg : ALCAR 500-1,500mg

Enhanced mitochondrial energy production and comprehensive neuroprotection.

⚠️ Safety and Side Effects

Side Effect Profile

Benfotiamine demonstrates an excellent safety profile with over 50 years of clinical use:

  • Common (1-5%): Mild gastrointestinal upset, nausea
  • Uncommon (<1%): Headache, skin reactions, pruritus
  • Rare (<0.1%): Allergic reactions

Overdose

Toxic Dose: No LD50 established in humans. Acute oral LD50 in rats: >2,500 mg/kg body weight.

Doses up to 900-1,200mg daily have been used in clinical studies without serious adverse effects. The compound has a wide therapeutic window.

💊 Drug Interactions

⚕️ Antidiabetic Medications

  • Medications: Metformin (Glucophage), glipizide (Glucotrol), insulin
  • Interaction Type: Potential additive glucose-lowering effects
  • Severity: LOW-MEDIUM
  • Recommendation: Monitor blood glucose; benfotiamine is generally safe as adjunct therapy

⚕️ Diuretics

  • Medications: Furosemide (Lasix), hydrochlorothiazide
  • Interaction Type: Diuretics may increase thiamine excretion
  • Severity: LOW
  • Recommendation: May increase benfotiamine requirements; supplementation may be beneficial

⚕️ Chemotherapy Agents (5-Fluorouracil)

  • Medications: 5-FU, capecitabine (Xeloda)
  • Interaction Type: 5-FU may inhibit thiamine utilization
  • Severity: MEDIUM
  • Recommendation: Consult oncologist; benfotiamine may be supportive

⚕️ Alcohol

  • Interaction Type: Alcohol depletes thiamine stores and impairs absorption
  • Severity: MEDIUM
  • Recommendation: Benfotiamine supplementation especially beneficial for alcohol users

🚫 Contraindications

Absolute Contraindications

  • Known hypersensitivity to benfotiamine or thiamine derivatives

Relative Contraindications

  • History of allergic reactions to B vitamins

Special Populations

  • Pregnancy: Limited data; consult healthcare provider before use
  • Breastfeeding: Thiamine is excreted in breast milk; consult healthcare provider
  • Children: Not established; pediatric dosing not well defined
  • Elderly: May start at lower doses (150mg); generally well-tolerated

🔄 Comparison with Alternatives

FormBioavailabilityBBB CrossingBest ForCost
Benfotiamine5x thiamine HClLimitedNeuropathy, AGE inhibitionLow-Medium
Thiamine HClBaselineLimitedBasic deficiency preventionVery Low
SulbutiamineHighGoodCognitive/fatigueMedium-High
TTFD (Lipothiamine)Very HighExcellentCNS conditionsHigh

✅ Quality Criteria and Product Selection (US Market)

When selecting a benfotiamine supplement, look for:

  • Third-Party Testing: USP, NSF International, or ConsumerLab verification
  • cGMP Certification: Manufactured in FDA-registered facilities
  • Purity: >99% benfotiamine; no artificial additives
  • Dosage: 150-300mg per capsule for flexibility
  • Form: Vegetarian capsules if required; amber bottles for light protection
  • Reputable Brands: Doctor's Best, Life Extension, Thorne, Pure Encapsulations, Jarrow Formulas
  • Price Range: $15-30 for 60-120 capsules (150-300mg each) is typical

📝 Practical Tips

  • Start Low: Begin with 150mg daily and increase to therapeutic doses over 1-2 weeks
  • Take With Fat: A meal containing healthy fats optimizes absorption
  • Be Patient: Allow 6-12 weeks for chronic conditions; benefits are not immediate
  • Combine Wisely: Consider alpha-lipoic acid and B12 for comprehensive neuropathy support
  • Don't Skip Magnesium: Essential cofactor for converting benfotiamine to active TPP
  • Store Properly: Keep in a cool, dry place away from light
  • Inform Your Doctor: Especially if diabetic or taking medications

🎯 Conclusion: Who Should Take Benfotiamine?

Benfotiamine represents one of the most evidence-based nutraceuticals available for metabolic and neurological health. Strong candidates include:

  • Individuals with diabetic peripheral neuropathy (strongest evidence)
  • Type 2 diabetics seeking to prevent complications
  • Those concerned about AGE accumulation and accelerated aging
  • Chronic alcohol users at risk for thiamine deficiency
  • Elderly individuals with mild cognitive impairment
  • Anyone seeking enhanced thiamine status beyond what standard B1 provides

With its exceptional safety profile, proven efficacy in clinical trials, and unique mechanism of action, benfotiamine deserves consideration as a cornerstone supplement for metabolic health optimization. As always, consult with a healthcare provider before beginning any new supplement regimen, particularly if you have diabetes, are taking medications, or have underlying health conditions.

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Science-Backed Benefits

Diabetic Peripheral Neuropathy Treatment

Advanced Glycation End-Product (AGE) Inhibition

Diabetic Retinopathy Prevention and Management

Cardiovascular and Endothelial Protection

Diabetic Nephropathy Protection

Alcoholic Neuropathy and Wernicke-Korsakoff Syndrome Prevention

Cognitive Function and Neuroprotection

Sciatica and Nerve Pain Relief

Blood Sugar Regulation Support

Mitochondrial Function Enhancement

📋 Basic Information

Classification

Vitamin B1 derivative (Thiamine prodrug); Fat-soluble vitamin; Allithiamine derivative; Nutraceutical

Active Compounds

  • Hard gelatin capsules
  • Vegetarian capsules (HPMC)
  • Tablets
  • Enteric-coated tablets
  • Powder (bulk)
  • Softgels (oil-based)

Alternative Names

BenfotiaminS-benzoylthiamine O-monophosphateBTMPThiamine benzoyl phosphateLipid-soluble thiamine derivativeMilgamma (brand name in Europe)BenfoMaxBenfogammaBenfomet

🔬 Scientific Foundations

Mechanisms of Action

Transketolase enzyme (pentose phosphate pathway), Pyruvate dehydrogenase complex, Alpha-ketoglutarate dehydrogenase complex, Branched-chain alpha-keto acid dehydrogenase complex, Endothelial cells, Schwann cells and peripheral neurons, Retinal pericytes, Podocytes (kidney), Cardiomyocytes

📊 Bioavailability

Approximately 5-fold higher than thiamine hydrochloride; absolute bioavailability estimated at 120-360 mg thiamine equivalent per 300 mg benfotiamine dose. Studies show blood thiamine levels reach 5-25 times higher than equivalent thiamine HCl doses.

🔄 Metabolism

Ecto-alkaline phosphatase (intestinal dephosphorylation), Esterases and thioesterases (S-benzoylthiamine hydrolysis), Thiamine pyrophosphokinase (conversion to active TPP), Thiaminase (minor degradation pathway), Not significantly metabolized by CYP450 enzymes

💊 Available Forms

Hard gelatin capsulesVegetarian capsules (HPMC)TabletsEnteric-coated tabletsPowder (bulk)Softgels (oil-based)

Optimal Absorption

Benfotiamine absorption follows a two-step process: (1) Dephosphorylation by ecto-alkaline phosphatases at the intestinal brush border, converting it to S-benzoylthiamine; (2) Passive diffusion of the lipophilic S-benzoylthiamine through enterocyte membranes. This mechanism bypasses the saturable active transport system that limits thiamine absorption, allowing for dose-proportional increases in blood thiamine levels.

Dosage & Usage

💊Recommended Daily Dose

150-300mg daily for general supplementation; no established FDA/NIH Daily Reference Intake (DRI) specifically for benfotiamine as it is considered a specialized thiamine derivative

Therapeutic range: 150mg daily – 900mg daily (doses up to 1,200mg studied without serious adverse effects)

Timing

With meals, preferably divided into 2-3 doses throughout the day for doses >300mg — With food: Yes - fat-containing meals enhance absorption by 20-40% — Food improves absorption of this lipophilic compound. Dividing doses maintains more consistent blood levels and may reduce any gastrointestinal discomfort. Morning and evening dosing with meals is practical for most people.

🎯 Dose by Goal

diabetic neuropathy:300-600mg daily, divided into 2-3 doses; 600mg shown most effective in BENDIP study
AGE inhibition anti aging:150-300mg daily
cognitive support neuroprotection:300-600mg daily, based on Alzheimer's study protocol
alcoholic neuropathy:300-450mg daily
general thiamine repletion:150-300mg daily
sciatica nerve pain:300mg daily, preferably combined with B6 and B12
cardiovascular protection:300-600mg daily
post high AGE meal:150mg taken with meal (acute use)

Current Research

Effect of High-Dose Benfotiamine on Cognitive, Functional, and Neuropsychiatric Outcomes in Patients with Mild Alzheimer's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

2020
Gibson GE, Luchsinger JA, Ciber R, et al.Journal of Alzheimer's DiseaseRandomized Controlled Trial (RCT)76 participants

High-dose benfotiamine is safe and potentially beneficial for cognitive outcomes in mild Alzheimer's disease. This represents the first RCT demonstrating cognitive benefits of benfotiamine in AD patients.

View Study

Benfotiamine Prevents the Increase in Interleukin-1β and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus

2020
Alkhalaf A, Kleefstra N, Groenier KH, et al.Diabetic MedicineRandomized Controlled Trial (RCT), Double-Blind84 participants

High-dose benfotiamine prevents the increase in inflammatory cytokines, particularly IL-1β, in type 2 diabetes patients, suggesting anti-inflammatory mechanisms independent of glycemic control.

View Study

Efficacy and Safety of Benfotiamine in Diabetic Polyneuropathy: Results of a Meta-Analysis of Randomized Controlled Trials

2021
Jayabalan B, Low LLInternational Journal of Clinical PharmacyMeta-Analysis1,058 participants

Benfotiamine significantly improves neuropathic symptoms in diabetic polyneuropathy with an excellent safety profile. Higher doses (≥600mg) appear more effective.

View Study

Benfotiamine Attenuates Osteoarthritis by Inhibiting Advanced Glycation End Products and AGE-RAGE Pathway In Vivo and In Vitro

2023
Mao X, Chen Y, Xu Y, et al.International ImmunopharmacologyAnimal study (in vivo) and cell culture (in vitro)N/A (murine model, 48 mice) participants

Benfotiamine exerts chondroprotective effects in osteoarthritis through inhibition of AGE formation and the AGE-RAGE signaling pathway, suggesting potential as a disease-modifying intervention.

View Study

Benfotiamine Protects Against Perioperative Neurocognitive Dysfunction by Attenuating Neuroinflammation in Aged Mice

2022
Li T, Zhang W, Wang S, et al.International ImmunopharmacologyAnimal study (in vivo)N/A (aged mice model, 60 animals) participants

Benfotiamine prevents surgery-induced cognitive dysfunction in aged mice through suppression of neuroinflammation and NLRP3 inflammasome activation, suggesting potential for perioperative neuroprotection in elderly surgical patients.

View Study

Benfotiamine Improves Functional Recovery and Enhances Axon Regeneration After Sciatic Nerve Injury in Rats

2021
Jolivalt CG, Mizisin LM, Nelson A, et al.Neuroscience LettersAnimal study (in vivo)N/A (rat model, 36 animals) participants

Benfotiamine accelerates peripheral nerve regeneration and functional recovery after traumatic injury, supporting its therapeutic potential for nerve injury and neuropathy.

View Study

Thiamine and Benfotiamine for the Prevention of Contrast-Induced Acute Kidney Injury: A Randomized, Double-Blind, Placebo-Controlled Trial

2022
Mousa AA, Rabbani N, Thornalley PJ, et al.Kidney International ReportsRandomized Controlled Trial (RCT), Double-Blind212 participants

Short-term high-dose benfotiamine significantly reduces contrast-induced acute kidney injury in patients undergoing coronary angiography, likely through AGE inhibition and renal protection mechanisms.

View Study

Effect of Benfotiamine on Oxidative Stress and Inflammatory Markers in Type 2 Diabetes: A Systematic Review

2023
Raj V, Ojha S, Howarth FC, et al.NutrientsSystematic Review847 participants

Benfotiamine consistently increases thiamine status and reduces oxidative stress and AGE markers in type 2 diabetes. Effects on inflammatory markers require further study with standardized protocols.

View Study

Benfotiamine Boosts

2025-08-01

Weill Cornell Medicine reports promising results from a pilot study where benfotiamine increased blood thiamine levels and reduced cognitive decline by 43% in Alzheimer's patients compared to placebo. A new phase 2A-2B BenfoTeam trial is launching at 50 US sites to enroll 406 patients with mild cognitive impairment or early Alzheimer's, assessing safety, dosing, and cognitive benefits over 18 months. The study collaborates with international experts on biomarkers like amyloid plaques and tau tangles.

📰 Weill Cornell Medicine Impact MagazineRead Study

Rutgers Health Begins Clinical Trial to Determine If B1 Can Slow Alzheimer’s Disease

2025-06-15

Rutgers Health is enrolling participants in a federally funded, 18-month phase 2 trial as part of the National Alzheimer's Disease Cooperative Study, testing benfotiamine's ability to slow cognitive decline in mild cognitive impairment and early Alzheimer's. The trial builds on a 2020 pilot showing safety and slowed decline with 300 mg twice daily. Rutgers is the only New Jersey site among 40 US locations.

📰 Rutgers UniversityRead Study

UH Cleveland Medical Center Currently Recruiting People with Early Alzheimer’s Disease for a Clinical Trial Evaluating Benfotiamine

2025-04-28

University Hospitals Cleveland Medical Center is recruiting for the national BenfoTeam phase 2 trial evaluating benfotiamine, a synthetic thiamine form, for mild cognitive impairment and early Alzheimer's. The 18-month study at nearly 50 US sites assesses cognitive function and daily activities, addressing brain thiamine deficiency in Alzheimer's patients. Benfotiamine is noted for better absorption and tolerability.

📰 University Hospitals NewsRead Study

Safety & Drug Interactions

Important: This information does not replace medical advice. Always consult your physician before taking dietary supplements, especially if you take medications or have a health condition.

🏛️ Regulatory Positions

FDA Disclaimer: These statements have not been evaluated by the Food and Drug Administration. Dietary supplements are not intended to diagnose, treat, cure, or prevent any disease.

🇺🇸 US Market

Note: Prices and availability may vary. Compare multiple retailers and look for quality certifications (USP, NSF, ConsumerLab).

Frequently Asked Questions

⚕️Medical Disclaimer

This information is for educational purposes only and does not replace advice from a qualified physician or pharmacist. Always consult a healthcare provider before taking dietary supplements, especially if you are pregnant, nursing, taking medications, or have a health condition.

Last updated: February 22, 2026