Description: <b>Dichloroacetate (DCA)</b> is a metabolic modulator that targets the altered metabolic state of cancer cells by inhibiting PDKs. This action impacts several key pathways:<br>
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• Reversal of the Warburg effect<br>
• Restoration of mitochondrial function and promotion of apoptosis<br>
• suppresses glycolysis and promotes oxidative phosphorylation, thereby increasing mitochondrial ROS-mediated apoptosis in tumor cells
• Increase in ROS production leading to oxidative stress<br>
• Inhibition of cell cycle progression<br>
• Modulation of HIF-1α signaling: DCA might decrease HIF-1α stabilization, thereby reducing the expression of genes that support glycolysis, angiogenesis, and survival under low-oxygen conditions.<br>
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-DCA has been primarily used in treating congenital lactic acidosis—a rare genetic disorder characterized by the buildup of lactic acid in the body.<br>
-DCA is an anti-diabetic and lipid-lowering drug, as well as treating myocardial and cerebrovascular ischemia.<br>
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-Do not add DCA to hot or warm beverages. DCA is unstable at higher temperatures<br>
-Caffeinated increases effectiveness<br>
-Vitamin B1 reduces neuropathy (500mg-2500mg/day)<br>
-Possibly 20 grams of citric acid 20 minutes before taking DCA<br>
-Procaine, Diclofenac or Sulindac to increase SMCT1 <br>
-Omeprazole 80mg/day to increase DCA effectiveness<br>
-Scorpion venom to increase DCA effectiveness <br>
-Metformin 1000mg to 1500mg/day<br>
-Propranolol (Ref.)<br>
-Fenbendazole shows strong synergy when combined to DCA, So it may make very much sense to combine the two.<br>
<a href="https://www.cancertreatmentsresearch.com/dichloroacetate-dca-treatment-strategy/">
"Note: DCA is not tumor cell specific,> and therefore the same shift in glucose metabolism that occurs in cancer cells will also take place in immune cells, leading to induction of Tregs (Ref.). In order to avoid this possibility, while using DCA I would also use Treg inhibitors such as Cimetidine (Ref.) or low dose Cyclophosphamide (Ref.)." </a><br>
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Dose: 10mg/kg/day and increase slowly to about 25mg/kg/day:(1/2morn,1/2evening) take 5 days on, 2 off? OR 2wks on/ 1wk off: https://www.thedcasite.com/dca_dosage.html<br>
Done by mixing it in water and drinking, suggested that DCA not be taken on an empty stomach.<br>
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**** <br>
DCA-induced apoptosis in cancer cells requires sodium-coupled monocarboxylates transporter SLC5A8 (SMCT1)<br>
-Inhibitors of DNA methylation induce reactivation of SLC5A8<br>
-Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells.<br>
-SMCT1 was found to be stimulated by some other NSAIDs (diclofenac, meclofenamate and sulindac), by activin A143 and by the probiotic Lactobacillus plantarum. <br>
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<a href="https://www.sciencedirect.com/science/article/pii/S2444866416300034"> SMCT1 has been found to be inhibited by some NSAIDs (ibuprofen, ketoprofen, fenoprofen, naproxen135 and indomethacin94), phytochemicals (resveratrol and quercetin) </a> **** Hence these should be avoided with DCA. (also AVOID Bromide, iodide and sulfite )<br>
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****<br>
GSTZ1 an/or chloride anion transport inhibitors also reduce resistance to DCA
(if the tumor expresses GSTZ1 and contains a high chloride anions level, the GSTZ1 will be stable, maintaining the resistance to DCA).<br>
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-<a href="https://www.cancertreatmentsresearch.com/">Dichloroacetate-dca-treatment-strategy </a>GSTZ1 an/or chloride anion transport inhibitors. .<br>
-<a href="http://www.ncbi.nlm.nih.gov/pubmed/1839837">Etacrynic acid is a Cl(-)-ATPase inhibitor </a> <br>
<a href="http://www.ncbi.nlm.nih.gov/pubmed/10711360">-Lansoprazole and Omeprazole inhibit chloride channels. </a><br>
-<a href="https://en.wikipedia.org/wiki/Chlorotoxin">Chlorotoxin found in scorpion venom (see my post on scorpion venom) can also inhibit chlorine channels </a> <br>
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Sources:<br>
<a href="https://northernhealthproducts.com/shop/" >https://northernhealthproducts.com/shop/</a> <br>
<a href="https://www.dcalab.com/">https://www.dcalab.com/ </a> <br>
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<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Target Axis</th>
<th>Direction</th>
<th>Primary Effect</th>
<th>Notes / Cancer Relevance</th>
<th>Ref</th>
</tr>
<tr>
<td>1</td>
<td>Pyruvate dehydrogenase kinase (PDK) → PDH gatekeeper</td>
<td>↓ PDK activity → ↑ active PDH (dephosphorylated)</td>
<td>Warburg reversal (pyruvate into TCA)</td>
<td>DCA’s canonical mechanism: inhibits PDK, restoring PDH activity and oxidative metabolism in cancer</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/20463368/">(ref)</a></td>
</tr>
<tr>
<td>2</td>
<td>Glycolysis output (lactate / ECAR)</td>
<td>↓ lactate production / ↓ ECAR</td>
<td>Reduced acidification; metabolic reprogramming</td>
<td>DCA decreases PDH phosphorylation and lowers glycolytic output (lactate/ECAR) in cancer models</td>
<td><a href="https://www.mdpi.com/1422-0067/21/24/9367">(ref)</a></td>
</tr>
<tr>
<td>3</td>
<td>Mitochondrial membrane potential remodeling (ΔΨm)</td>
<td>↓ cancer-associated mitochondrial hyperpolarization (depolarization)</td>
<td>Restores apoptosis susceptibility</td>
<td>Glioblastoma work: DCA reverses cancer-specific mitochondrial remodeling (hyperpolarization → depolarization), enabling apoptosis</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/20463368/">(ref)</a></td>
</tr>
<tr>
<td>4</td>
<td>ROS generation (especially under hypoxia)</td>
<td>↑ ROS</td>
<td>Oxidative stress trigger</td>
<td>DCA increases ROS in hypoxic cancer cells (reported strongly under hypoxia), linking metabolic shift to cytotoxic stress</td>
<td><a href="https://www.mdpi.com/1422-0067/21/24/9367">(ref)</a></td>
</tr>
<tr>
<td>5</td>
<td>Voltage-gated K+ channel axis (Kv1.5) / NFAT signaling</td>
<td>↑ Kv1.5 expression/activity</td>
<td>Pro-apoptotic electrophysiology shift</td>
<td>Endometrial cancer study: DCA engages mitochondrial + NFAT–Kv1.5 mechanisms associated with apoptosis sensitization</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/18423823/">(ref)</a></td>
</tr>
<tr>
<td>6</td>
<td>Intrinsic apoptosis (mitochondrial pathway)</td>
<td>↑ apoptosis</td>
<td>Programmed cell death</td>
<td>DCA induces apoptosis in glioblastoma and endometrial cancer models as mitochondrial remodeling is reversed</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/20463368/">(ref)</a></td>
</tr>
<tr>
<td>7</td>
<td>PUMA-mediated apoptotic priming</td>
<td>↑ PUMA-dependent sensitization</td>
<td>Lower apoptotic threshold</td>
<td>Endometrial cancer paper explicitly reports a PUMA-mediated component in DCA apoptosis sensitization</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/18423823/">(ref)</a></td>
</tr>
<tr>
<td>8</td>
<td>Hypoxia resistance axis (HIF-1α / PDK1)</td>
<td>↓ hypoxia-associated resistance (HIF-1α/PDK1 axis engaged)</td>
<td>Improved treatment responsiveness</td>
<td>DCA attenuates hypoxia-associated resistance in gastric cancer context with reported linkage to HIF-1α and PDK1</td>
<td><a href="https://www.sciencedirect.com/science/article/abs/pii/S0014482713005260">(ref)</a></td>
</tr>
<tr>
<td>9</td>
<td>Radiosensitization (hypoxic tumor cells)</td>
<td>↑ radiosensitivity (esp. under hypoxia)</td>
<td>Therapy potentiation</td>
<td>DCA increases ROS under hypoxia and enhances radiotherapy response in TNBC models</td>
<td><a href="https://www.mdpi.com/1422-0067/21/24/9367">(ref)</a></td>
</tr>
<tr>
<td>10</td>
<td>In vivo / translational anti-tumor activity (glioblastoma)</td>
<td>↓ tumor growth / ↓ proliferation (model-dependent)</td>
<td>Demonstrated anti-tumor effect</td>
<td>Glioblastoma study includes translational evidence that DCA can reverse tumor metabolic remodeling with anti-tumor effects</td>
<td><a href="https://pubmed.ncbi.nlm.nih.gov/20463368/">(ref)</a></td>
</tr>
</table>