Dichloroacetate (DCA) is a small molecule that shifts how cells make energy. By inhibiting pyruvate dehydrogenase kinase (PDK), it activates the pyruvate dehydrogenase complex (PDH) and nudges metabolism away from glycolysis toward mitochondrial oxidation. Clinically, that has meant two main areas of interest: lowering elevated lactate in congenital or acquired lactic acidosis, and modulating tumor metabolism as an add-on to standard cancer therapies. It is not a dietary supplement and is not approved as a cancer treatment. Research continues, with dosing, safety, and who might benefit most shaped by age, genetics, and the presence of peripheral neuropathy. If you are considering DCA, do so only within a clinical trial or under a specialist’s supervision, because dose selection, monitoring, and drug quality control materially affect risk.
Essential Insights for DCA Users
- May lower elevated lactate and support mitochondrial oxidation in selected settings.
- Investigational as an add-on in cancer; evidence shows mixed efficacy and emphasizes safety monitoring.
- Typical research doses: 6.25–12.5 mg/kg twice daily (≈12.5–25 mg/kg/day) under medical supervision.
- Safety caveat: dose- and duration-related peripheral neuropathy; monitor sensations in hands and feet.
- Avoid if pregnant, trying to conceive, breastfeeding, or if you have active neuropathy or significant liver disease.
Table of Contents
- What is dichloroacetate (DCA)?
- Does DCA work and for what?
- How to use DCA safely
- How much DCA per day?
- Side effects, interactions, and warnings
- What does the evidence say?
What is dichloroacetate (DCA)?
Dichloroacetate (usually taken as the sodium salt) is a simple, halogenated carboxylic acid that alters cellular energy use. Its primary target is pyruvate dehydrogenase kinase (PDK), a family of enzymes that inactivate the pyruvate dehydrogenase complex (PDH)—the gatekeeper that channels pyruvate into the mitochondria to become acetyl-CoA. When PDK is inhibited, PDH activity rises, glycolysis slows, and cells favor oxidative phosphorylation. This shift can reduce lactate formation and change the tumor microenvironment’s acidity, two reasons DCA has drawn clinical interest.
Metabolically, DCA is broken down mainly in the liver and kidney by glutathione S-transferase zeta 1 (GSTZ1), also known as maleylacetoacetate isomerase. That metabolism can be autoinhibited by DCA itself and is influenced by GSTZ1 genetic variants and age. In practical terms, older adults tend to clear DCA more slowly, and certain GSTZ1 haplotypes predispose to higher exposure. These factors help explain why dose, schedule, and monitoring matter.
Importantly, DCA has a different regulatory status than popular over-the-counter supplements. It is not approved as an anticancer drug, and there is no widely accepted retail “supplement-grade” standard for it. Clinical research has used pharmaceutical-grade material, defined capsule strengths, and formal oversight. For safety, avoid unregulated sources and do not self-dose.
Where has DCA been studied?
- Congenital or acquired lactic acidosis (including disorders involving PDH complex function).
- Oncology, primarily as a metabolic adjuvant alongside chemotherapy and/or radiotherapy (e.g., in head and neck cancer).
- Additional exploratory areas include ischemia-reperfusion, sepsis, and metabolic complications, though these are not routine indications.
Bottom line: DCA is a metabolic modulator, not a cure-all. Its potential benefits arise from a clear biochemical mechanism, but real-world outcomes depend on diagnosis, dose, combination therapy, and patient factors.
Does DCA work and for what?
Lactic acidosis and mitochondrial disorders. Because DCA increases PDH activity, it reliably lowers lactate in many contexts of impaired oxidative metabolism. In congenital lactic acidosis and PDH-related disorders, reductions in blood or cerebrospinal fluid lactate have been observed. That said, biochemical improvement does not guarantee clinical benefit. Some studies report limited or no improvements in survival or neurologic outcomes despite lactate reductions. This divergence underscores the need for precise diagnosis (e.g., which mitochondrial enzyme is affected) and for goals that extend beyond a lab value.
Cancer metabolism (adjuvant use). Many tumors preferentially use glycolysis even in oxygenated conditions (the “Warburg effect”), leading to excess lactate and an acidic microenvironment that can suppress immune function and promote invasion. By pushing metabolism toward mitochondrial oxidation, DCA may reduce lactate, alter pH, and potentially improve response to standard therapy. The most informative trials to date have tested DCA as an add-on rather than as stand-alone treatment. In locally advanced head and neck cancer, adding DCA during chemoradiotherapy defined a feasible dose, showed a broadly similar safety profile to placebo for most adverse events, and did not clearly improve efficacy endpoints. These results suggest that while DCA is biologically active and generally manageable when monitored, its clinical impact may depend on the cancer type, combination partners, dosing, and patient selection.
Who might benefit?
- Patients with documented PDH complex dysfunction or specific metabolic phenotypes may experience clearer biochemical effects (lactate reduction).
- In oncology, combination strategies are being explored (e.g., with chemoradiotherapy or other metabolic agents). Early preclinical work suggests synergy with drugs like metformin, but clinical translation remains incomplete.
Who is unlikely to benefit?
- People seeking a stand-alone “alternative” cancer therapy: the evidence does not support DCA as a replacement for established treatments.
- Individuals without a clear metabolic indication or a supervising clinician: dosing errors and neuropathy risks can outweigh theoretical gains.
Key nuance: Outcomes vary by dose, duration, age, GSTZ1 genotype, and co-medications. DCA’s capacity to autoinhibit its own metabolism means exposure can increase over time—part of why careful scheduling and surveillance matter. The most responsible use of DCA today is within clinical trials or specialist-managed regimens that tie dosing to monitoring and patient-specific risk.
How to use DCA safely
DCA should be used only under medical supervision or in a clinical trial. Safety rests on three pillars: fit, quality, and monitoring.
1) Confirm the fit.
- Clarify the indication: congenital lactic acidosis/PDH-related disorders vs an oncology add-on.
- Review prior treatments and neuropathy history. DCA’s main dose-limiting toxicity is peripheral neuropathy; pre-existing paresthesias amplify risk.
- Consider genetic and age factors. Older adults and certain GSTZ1 haplotypes show slower clearance and higher exposure; clinicians may choose lower starting doses or longer intervals.
2) Insist on quality.
- Pharmaceutical-grade material with known capsule strength is essential. Avoid unverified online products.
- If part of a trial, dosing and blinding will be standardized; outside trials, clinicians should specify exact strengths (e.g., 125 mg, 250 mg, 500 mg capsules) and compounding standards.
3) Set a monitoring plan before the first dose.
Baseline:
- Neurologic exam (vibration, pinprick, proprioception; symptom inventory).
- Liver enzymes (ALT/AST), bilirubin, alkaline phosphatase; consider GGT.
- Renal function, CBC (to track thrombocytopenia risk with certain combinations).
- Nutrient review: low thiamine (vitamin B1) may plausibly worsen risk; many protocols give empiric thiamine (e.g., 50–100 mg/day) though definitive evidence is limited.
- Pregnancy test when relevant; DCA crosses the placenta in animal models, so pregnancy is a hard stop.
During therapy:
- Neuropathy check weekly early on, then each visit: numbness, tingling, burning, gait change.
- Liver enzymes every 2–4 weeks initially, then at a clinician-determined interval.
- Dose adjustments or holds for persistent grade 2 neurologic symptoms or lab abnormalities, with re-challenge only after recovery and risk re-assessment.
Practical use tips (clinician-directed):
- Take capsules with food to lessen GI upset.
- Avoid alcohol excess and sedatives that can compound drowsiness reported at higher DCA doses.
- Be cautious with concurrent neurotoxic chemotherapies (e.g., platinum agents); coordinate timing and symptom tracking.
- Document exact mg/kg and review weight changes periodically to avoid inadvertent overdosing during long courses.
Red flags to stop and call the team immediately:
- New or rapidly worsening numbness, burning pain, or weakness.
- Marked fatigue, jaundice, dark urine, or right-upper-quadrant pain.
- Persistent vomiting, confusion, severe headache, or any signs of encephalopathy.
Bottom line: A sound plan pairs appropriate patients with verified drug supply and tight surveillance. That is the safest path to test whether DCA offers benefit in your specific situation.
How much DCA per day?
All dosing below is investigational and should be used only in trials or specialist-supervised care.
Common research ranges:
- 6.25–12.5 mg/kg twice daily (≈ 12.5–25 mg/kg/day) are the most frequently studied oral regimens in adults. These schedules come from oncology and metabolic trials that prioritized tolerability and pharmacokinetic predictability.
- Some protocols start lower (e.g., 5–6 mg/kg twice daily) for older adults or those with risk factors, then titrate if tolerated.
- Doses >25 mg/kg/day have been linked to increased sedation/drowsiness and a higher risk of neuropathy, particularly with prolonged courses.
Why body-weight dosing? DCA exposure varies with weight, age, and GSTZ1 genotype. Weight-based dosing keeps initial exposure more consistent across patients, but clinicians still adjust by response and labs.
Worked examples (for illustration only):
- 70-kg adult: 12.5 mg/kg twice daily → 875 mg BID (total 1,750 mg/day).
- 60-kg adult: 6.25 mg/kg twice daily → 375 mg BID (total 750 mg/day) as a cautious starting point in higher-risk patients.
- 90-kg adult: 12.5 mg/kg twice daily → 1,125 mg BID (total 2,250 mg/day); rounding to available capsule strengths is routine (e.g., 1,000–1,250 mg).
Course length:
- In oncology, DCA is typically given throughout chemoradiotherapy (for example, for the 6–7-week radiation course) or for a defined number of cycles with chemotherapy.
- In metabolic indications, courses vary widely; some centers use intermittent schedules (e.g., several weeks on, followed by an off period) to limit cumulative neuropathy.
Adjustments and holds:
- Neurologic symptoms: hold for persistent grade 2 (or worse) neuropathy; re-start at a lower dose only after recovery.
- Liver test elevations: follow the program’s stopping rules (often hold if ALT/AST ≥3× ULN or if symptoms occur).
- Age/genetics: lower initial targets or slower uptitration may be used in older adults or in known slow DCA metabolizers.
Co-factors and supportive care:
- Thiamine (vitamin B1) is often given empirically (e.g., 50–100 mg/day) to support oxidative pathways; while mechanistic rationale exists, this practice is based more on plausibility than definitive randomized evidence.
- Maintain adequate hydration and balanced nutrition; avoid excessive alcohol.
Important: Do not treat these figures as over-the-counter guidance. They are clinical research doses used with lab checks, neurologic exams, and pre-specified stopping rules.
Side effects, interactions, and warnings
Most common, dose-shaping effect: peripheral neuropathy.
Patients describe tingling, numbness, burning, or reduced vibration sense in a stocking-glove pattern. Risk rises with higher daily dose, longer duration, older age, and possibly GSTZ1 variants that slow metabolism. Early detection matters: dose holds at the first persistent grade 2 symptoms reduce the chance of long-term deficits. In many reports, neuropathy improves after stopping DCA, though recovery can take weeks.
Central nervous system effects.
At doses above ~25 mg/kg/day, some patients experience sedation or drowsiness. This tends to remit with dose reduction or discontinuation.
Gastrointestinal and general effects.
Nausea, dyspepsia, and anorexia can occur, especially during combination chemoradiotherapy. Taking DCA with food helps some patients. Weight loss in oncology cohorts often relates more to the underlying treatment course than to DCA itself.
Liver and blood.
Increases in ALT/AST have been observed in preclinical models at very high exposures; routine monitoring is prudent in humans, particularly when other hepatotoxic drugs are used. One randomized oncology study noted non-severe thrombocytopenia more frequently in the DCA arm; comprehensive lab surveillance remains advisable.
Serious but less common events.
- Encephalopathy has been reported rarely, including at moderate doses in case literature; any confusion or severe headache warrants immediate evaluation.
- A fatal case of liver and bone marrow toxicity occurred with an unregulated combination of DCA plus artesunate administered by an alternative practitioner—illustrating the importance of avoiding unsupervised mixtures and verifying drug quality.
Drug and condition interactions.
- Neurotoxic agents (e.g., platinum chemotherapy, certain antivirals, or high-dose B6) may compound neuropathy risk.
- Sedatives/alcohol can worsen drowsiness.
- Pregnancy and breastfeeding: avoid; animal data show placental transfer, and safety for the fetus/infant is unknown.
- Pre-existing neuropathy, uncontrolled liver disease, or severe malnutrition: higher-risk groups; many clinicians avoid DCA or use lower starting doses with tight monitoring.
Allergy and hypersensitivity.
True allergic reactions are uncommon but possible with any drug. Seek care for rash, wheeze, or swelling after dosing.
Quality and sourcing warning.
Because DCA is not an approved supplement, supply chain quality varies. Pharmaceutical-grade material used in trials is not interchangeable with internet products. Impurities and wrong strengths can magnify toxicity.
What to do if symptoms appear.
Report neurologic changes promptly; dose holds and reassessments are the norm. Resume only if symptoms resolve and your care team judges the benefit-risk favorable.
What does the evidence say?
Mechanism is solid; outcomes depend on context. DCA’s biochemistry—PDK inhibition with activation of PDH—is well documented. It can lower lactate and shift tumor metabolism toward oxidation. Yet clinical outcomes hinge on indication, combination partners, dose, and patient selection.
Lactic acidosis and PDH-related disorders. Clinical and translational work shows consistent lactate reductions with DCA, but mixed clinical results in neurologic function or survival. A key insight is heterogeneity: congenital lactic acidosis represents many different genetic defects. Patients with PDH complex involvement may respond more predictably than those with electron transport chain defects, but results still vary. Reviews comparing DCA with alternatives such as phenylbutyrate emphasize mutation-specific responsiveness and the need for individualized plans.
Oncology. In a randomized, placebo-controlled addition of DCA to cisplatin-based chemoradiotherapy for locally advanced head and neck cancer, investigators established a tolerable oral dose (12.5 mg/kg twice daily) with structured neuropathy monitoring. Safety was broadly similar to placebo for most adverse events, and efficacy endpoints did not clearly improve by adding DCA. Preclinical studies continue to explore combinations (e.g., with metformin or 5-FU), and clinical research is probing where metabolic reprogramming could help—potentially in tumors with high lactate flux or specific PDK expression patterns.
Pharmacokinetics and personalization. DCA is metabolized by GSTZ1, and chronic dosing autoinhibits its own clearance. Age and GSTZ1 polymorphisms affect exposure, supporting the case for weight-based dosing, cautious uptitration, and vigilant monitoring. Animal data show placental transfer, prompting pregnancy avoidance.
Safety perspective. The dose-limiting toxicity is peripheral neuropathy—reversible in many cases upon drug cessation—plus occasional sedation at higher daily doses. With attentive monitoring, many programs keep neuropathy at manageable levels by pausing or dose-reducing at the earliest signs. Rare severe events underscore the need to avoid unsupervised combinations and to rely on clean drug supply.
Take-home: DCA is biologically active and clinically testable, but it is not a stand-alone cure. The most responsible path is within trials or specialist-guided protocols that match dosing to indication, genetics, and risk—and that prioritize patient-centered outcomes beyond a single lab value.
References
- Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma 2022 (RCT)
- Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger 2023 (Systematic Review)
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts 2024 (Systematic Review)
- Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency 2022 (Review)
- Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses 2021 (PK/Safety)
Disclaimer
This article is informational and does not constitute medical advice. Dichloroacetate (DCA) is an investigational therapy and is not approved to treat cancer or most metabolic conditions. Do not start, stop, or change any medication or dosing without guidance from your qualified healthcare professional. If you are pregnant, planning pregnancy, breastfeeding, or have significant neuropathy or liver disease, discuss risks with your clinician; DCA may be inappropriate.
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