Description: <b>VitB1/Thiamine</b><br>
Vitamin B1 (thiamine) is an essential water-soluble vitamin required for carbohydrate metabolism and mitochondrial energy production. Its active form, thiamine pyrophosphate (TPP), is a cofactor for key enzymes including pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (α-KGDH), and transketolase. In Alzheimer’s disease (AD), thiamine deficiency and reduced activity of thiamine-dependent enzymes have been repeatedly observed in brain tissue. Impaired glucose metabolism is a hallmark of AD (“type 3 diabetes” hypothesis), and thiamine-dependent enzyme dysfunction contributes to mitochondrial impairment, oxidative stress, and neuronal vulnerability. Experimental studies suggest thiamine and lipophilic derivatives (e.g., benfotiamine) may improve glucose metabolism, reduce advanced glycation end products (AGEs), attenuate oxidative stress, and modulate neuroinflammation. Clinical data are mixed but suggest possible benefit in selected populations or with higher-bioavailability derivatives.<br>
Benfotiamine is a fat-soluble derivative of vitamin B1 (thiamine) that’s used to support nerve health, glucose metabolism, and potentially brain function, including in conditions like Alzheimer’s disease (AD) and diabetic neuropathy.<br>
-fat-soluble form, so may absorb better when taken with a meal containing fat.<br>
<pre>
Condition / Purpose Typical Dose Range Notes
Alzheimer’s Disease (AD) 300–600 mg/day Used in clinical trials (e.g., 300 mg twice daily)
Diabetic Neuropathy 300–600 mg/day Most common clinical application
General Cognitive Support 150–300 mg/day Lower end for maintenance
High-dose experimental use 900–1,200 mg/day Occasionally used under supervision in research
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<h3>Alzheimer’s Disease Table: Vitamin B1 (Thiamine)</h3>
<!-- Alzheimer’s Disease Table: Vitamin B1 (Thiamine) -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>AD / Neurodegeneration Context</th>
<th>Normal Brain Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Pyruvate dehydrogenase (PDH) activity</td>
<td>PDH activity ↓ in AD; thiamine restores PDH flux</td>
<td>Glucose oxidation support</td>
<td>R, G</td>
<td>Mitochondrial energy restoration</td>
<td>PDH links glycolysis to TCA cycle; impairment contributes to cerebral hypometabolism in AD.</td>
</tr>
<tr>
<td>2</td>
<td>α-Ketoglutarate dehydrogenase (α-KGDH)</td>
<td>α-KGDH ↓ in AD brain tissue</td>
<td>TCA cycle support</td>
<td>R, G</td>
<td>Mitochondrial stabilization</td>
<td>Enzyme reduction correlates with oxidative stress and neuronal vulnerability.</td>
</tr>
<tr>
<td>3</td>
<td>Transketolase / Pentose Phosphate Pathway (PPP)</td>
<td>NADPH production ↑; oxidative stress ↓</td>
<td>Redox buffering</td>
<td>R, G</td>
<td>Antioxidant support</td>
<td>Transketolase requires thiamine; PPP supports glutathione regeneration.</td>
</tr>
<tr>
<td>4</td>
<td>Mitochondrial bioenergetics</td>
<td>ATP production ↑; mitochondrial efficiency ↑</td>
<td>Energy metabolism normalization</td>
<td>R</td>
<td>Bioenergetic restoration</td>
<td>Addresses cerebral glucose hypometabolism seen in AD imaging studies.</td>
</tr>
<tr>
<td>5</td>
<td>Oxidative stress reduction</td>
<td>ROS ↓; lipid peroxidation ↓ (reported)</td>
<td>Redox balance support</td>
<td>R, G</td>
<td>Antioxidant effect (indirect)</td>
<td>Improved mitochondrial function reduces ROS generation.</td>
</tr>
<tr>
<td>6</td>
<td>Advanced glycation end products (AGEs)</td>
<td>AGE formation ↓ (reported with benfotiamine)</td>
<td>Glycation moderation</td>
<td>G</td>
<td>Metabolic toxicity reduction</td>
<td>Benfotiamine may reduce glycation-linked neuronal damage.</td>
</tr>
<tr>
<td>7</td>
<td>Neuroinflammation</td>
<td>Inflammatory markers ↓ (model-dependent)</td>
<td>Inflammation moderation</td>
<td>R, G</td>
<td>Secondary anti-inflammatory effect</td>
<td>Likely indirect via improved metabolic and redox function.</td>
</tr>
<tr>
<td>8</td>
<td>Amyloid / tau pathology</td>
<td>Indirect modulation reported in models</td>
<td>↔</td>
<td>G</td>
<td>Disease-modifying potential (uncertain)</td>
<td>No strong direct anti-amyloid mechanism; effects appear metabolic.</td>
</tr>
<tr>
<td>9</td>
<td>Clinical cognition outcomes</td>
<td>Mixed results; some benefit with benfotiamine</td>
<td>Safe at standard doses</td>
<td>G</td>
<td>Adjunctive support</td>
<td>High-dose or derivative forms may show more promise than standard thiamine.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability / derivative consideration</td>
<td>Benfotiamine & lipid-soluble forms ↑ CNS penetration</td>
<td>Well tolerated</td>
<td>—</td>
<td>Translation constraint</td>
<td>Standard thiamine has limited brain penetration; benfotiamine shows improved pharmacokinetics.</td>
</tr>
</table>
<p><small>
TSF: P = minimal immediate effect; R = metabolic enzyme activation; G = long-term neuroprotective adaptation.
</small></p>
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<h3>Thiamine vs Benfotiamine Comparison Table</h3>
<!-- Thiamine vs Benfotiamine Comparison Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Feature</th>
<th>Thiamine (Vitamin B1)</th>
<th>Benfotiamine</th>
</tr>
<tr>
<td>Chemical form</td>
<td>Water-soluble vitamin (thiamine hydrochloride or mononitrate)</td>
<td>Lipid-soluble S-acyl thiamine derivative</td>
</tr>
<tr>
<td>Absorption mechanism</td>
<td>Active transport (THTR-1/2) in small intestine</td>
<td>Passive diffusion (lipophilic); higher bioavailability</td>
</tr>
<tr>
<td>Plasma thiamine levels</td>
<td>Moderate increase with supplementation</td>
<td>Significantly higher plasma thiamine after oral dosing</td>
</tr>
<tr>
<td>Brain penetration</td>
<td>Limited; regulated transport</td>
<td>Indirectly increases brain thiamine via systemic elevation; better tissue distribution</td>
</tr>
<tr>
<td>Activation</td>
<td>Converted to thiamine pyrophosphate (TPP) intracellularly</td>
<td>Converted to thiamine → TPP intracellularly</td>
</tr>
<tr>
<td>PDH / α-KGDH support</td>
<td>Restores enzyme activity in deficiency</td>
<td>Stronger elevation of transketolase & TPP-dependent activity (reported)</td>
</tr>
<tr>
<td>Pentose phosphate pathway (PPP)</td>
<td>Supports transketolase → NADPH production</td>
<td>More pronounced activation of transketolase reported</td>
</tr>
<tr>
<td>AGE reduction</td>
<td>Limited direct evidence</td>
<td>Strong evidence for reducing advanced glycation end products (AGEs)</td>
</tr>
<tr>
<td>Oxidative stress impact</td>
<td>Indirect ROS reduction via improved metabolism</td>
<td>Stronger reduction of glycation-related oxidative stress</td>
</tr>
<tr>
<td>AD clinical evidence</td>
<td>Mixed, limited benefit in trials</td>
<td>Small trials suggest potential cognitive stabilization</td>
</tr>
<tr>
<td>Dose ranges studied (AD/metabolic)</td>
<td>100–300 mg/day (varies)</td>
<td>150–600 mg/day commonly studied</td>
</tr>
<tr>
<td>Safety profile</td>
<td>Very safe; excess excreted in urine</td>
<td>Generally safe; mild GI symptoms possible</td>
</tr>
<tr>
<td>Primary AD positioning</td>
<td>Correct deficiency; metabolic support</td>
<td>Enhanced metabolic + anti-glycation support</td>
</tr>
<tr>
<td>Best-fit scenario</td>
<td>Thiamine deficiency; mild metabolic impairment</td>
<td>Glucose dysregulation; high AGE burden; metabolic AD phenotype</td>
</tr>
</table>