Mitochondrial Dysfunction

Why it works: Stimulates mitochondrial biogenesis and function. Endurance and resistance training up-regulate PGC-1α signaling and downstream nuclear-encoded mitochondrial genes, increasing mito...

Instructions: Before you start. • Get medical and cardiac screening (PMD can involve cardiomyopathy/conduction disease). Ideally review at a specialist mitochondrial centre and with a physiother...

Warnings: Cardiac involvement: Because PMD can include cardiomyopathy/conduction disease, obtain cardiology sc...

Studies: Aerobic training improves capacity and is safe in PMD. Class...

Why it works: A cleaner, mitochondria-friendly fuel. Ketone bodies (β-hydroxybutyrate, acetoacetate) yield more ATP per unit oxygen than glucose in many tissues, can raise the cellular NAD⁺/NADH...

Instructions: 1) Pre-diet screening. • Confirm indication (e.g., refractory epilepsy in PMD; selected non-seizure indications on a case-by-case basis). mitoaction.org. • Rule out absolute contra...

Warnings: Absolute or major contraindications (screen before starting):. • Fatty-acid oxidation defects (e.g.,...

Studies: Systematic review (PMD-focused). A 2021 Orphanet Journal of...

Why it works: Redox & anti-inflammatory effects that protect mitochondria. Curcumin scavenges ROS and dampens NF-κB–driven inflammation—two drivers of mitochondrial damage. Reviews summarise tha...

Instructions: 1) Choose an evidence-based form.. Curcumin is poorly absorbed. You can either:. • Take standard curcumin with piperine (black pepper extract) to increase absorption (shown up to ~...

Warnings: Liver injury (rare but documented): Australia’s TGA safety alert concludes there is a rare risk of l...

Studies: Direct human RCTs in primary mitochondrial disease are lacki...

Why it works: SIRT1/AMPK → PGC-1α → mitochondrial biogenesis & oxidative metabolism. RSV activates nutrient-sensing pathways (SIRT1 and AMPK), which can up-regulate PGC-1α, NRF1/2 and TFAM—key d...

Instructions: Form: look for trans-resveratrol from a reputable brand with third-party testing (e.g., USP/NSF). (General safety and supplement-quality guidance in consumer-health overviews.) Ver...

Warnings: Bleeding risk & drug interactions: RSV has antiplatelet activity; combined use with anticoagulants/a...

Studies: Human studies (not primary mitochondrial disease):Obese men,...

Why it works: Mild Complex I inhibition → AMPK activation (mitohormesis): Berberine directly inhibits mitochondrial respiratory chain Complex I, creating a small energetic stress that activates...

Instructions: Form & dose commonly studied. • Berberine HCl: Most human metabolic trials use 500 mg 2–3×/day (total 1,000–1,500 mg/day), often with or just before meals to improve GI tolerance a...

Warnings: Pregnancy, breastfeeding, and infants: avoid. Berberine can worsen neonatal jaundice and has been li...

Studies: Human trials & meta-analyses (mitochondria-relevant outc...

Why it works: Targets mitochondrial biogenesis/signaling (preclinical): A recent Journal of Ethnopharmacology paper reports DHYZ activates the AMPK–SIRT1–PGC-1α axis, promoting mitochondrial bio...

Instructions: Please treat this as general information — because DHYZ contains aconite (Fu Zi), a potentially cardiotoxic herb, safe use requires a qualified practitioner.. • Classical compositi...

Warnings: Because DHYZ includes Fu Zi (processed aconite) and Rou Gui (cinnamon bark) along with other active...

Studies: Preclinical (mitochondrial mechanisms):AMPK–SIRT1–PGC-1α act...

Why it works: Restores fatty-acid entry into mitochondria. L-carnitine is the carrier for long-chain fatty acids across the mitochondrial membranes via the CPT1–CACT–CPT2 “carnitine shuttle,” en...

Instructions: Formulations: L-carnitine (levocarnitine) oral solution/tablets; IV formulations exist for acute/ inpatient use. (Reference monographs.) Medscape. Common outpatient oral dose range...

Warnings: Common side effects: GI upset (nausea, cramps, diarrhea) and fishy body odor, more likely at ≈3 g/da...

Studies: Randomized, double-blind, crossover RCT (CPEO/mitochondrial...

Why it works: Restores “cellular cleanup” (autophagy/mitophagy). Spermidine is a nutrient-sensing polyamine that pharmacologically induces autophagy—including selective turnover of damaged mitoc...

Instructions: Form & standardization. • Human studies and regulatory filings refer to a spermidine-rich wheat-germ extract. In the EU, this ingredient is an authorized “novel food” with a define...

Warnings: Pregnancy & lactation: Do not use spermidine-rich wheat-germ extract during pregnancy or breastfeedi...

Studies: Human evidence (no mitochondrial endpoints yet):RCT in older...

Why it works: Triggers mitochondrial biogenesis (preclinical). In cell and animal models, PQQ activates CREB → PGC-1α with downstream NRF-1/NRF-2 and TFAM, increasing mtDNA copy number, citrate...

Instructions: Form & dose used in studies: Most human studies used PQQ disodium salt (often branded) at 20 mg/day, typically with food, for 6–12 weeks. This is also the maximum daily intake EFSA...

Warnings: Population limits: EFSA’s opinion allows up to 20 mg/day in healthy adults and specifically excludes...

Studies: Mechanism & translational groundworkJBC 2010 (mouse hepa...

Why it works: Core role in mitochondrial energy: CoQ10 (ubiquinone/ubiquinol) shuttles electrons between complexes I/II → III in the mitochondrial electron transport chain (ETC). That’s central...

Instructions: Form: Both ubiquinone and ubiquinol are used. Ubiquinol generally shows higher bioavailability; regardless of the form taken, most circulating CoQ10 becomes ubiquinol. Take with a...

Warnings: Anticoagulants (warfarin): possible interaction — CoQ10 may reduce warfarin’s anticoagulant effect (...

Studies: Consensus statement (Mitochondrial Medicine Society, 2015; u...

Why it works: Biochemical role. Riboflavin is the precursor of the redox coenzymes FMN and FAD, which are required by dozens of mitochondrial flavoproteins, including Complex I (FMN) and Complex...

Instructions: 1) Riboflavin-responsive MADD (ETFDH/ETFA/EFTB). • Dose (adults & adolescents): 100–300 mg/day oral, typically in 2–3 divided doses; continue long-term if responsive. SpringerLink....

Warnings: General safety: Riboflavin is water-soluble; no UL has been set. Even 400 mg/day for ≥3 months hasn’...

Studies: Mechanistic & review evidenceComprehensive reviews detai...