Mitochondria and Energy

1. What This Mechanism of Action Is

Mitochondria are the cell’s central powerhouses and regulate aerobic energy production through oxidative phosphorylation. They also control autophagy, a process that breaks down and recycles damaged cellular components. Disruptions in these processes lead to energy deficits, oxidative stress, and the accumulation of cellular waste products. This manifests as reduced physical and cognitive performance as well as increased fatigue. The substances involved act in various ways: as cofactors in the respiratory chain, as antioxidants, as inflammation modulators, or by supporting mitochondrial biogenesis.

Measuring mitochondrial function in humans is challenging. Direct analyses require tissue samples, which must be obtained invasively. Indirect markers such as ATP levels, lactate production, or oxidative stress parameters are less specific and are influenced by numerous factors. Subjective parameters like fatigue or performance capacity are also difficult to objectify. Controlled studies therefore often use combinations of biomarkers, imaging, and clinical scores to assess effects.

2. Which Substances Are Associated with It

All substances in the database for which this mechanism of action is described—ordered by the extent of human testing. The numbers represent studies per type of investigation.

3. How Robust This Evidence Is

Substances such as coenzyme Q10, L-carnitine, and chronic inflammation are well supported by a large number of human studies and controlled investigations. For example, coenzyme Q10 demonstrates effects on mitochondrial function and performance in 26 controlled studies. Resveratrol, melatonin, and vitamin D also have a solid evidence base. In contrast, substances such as humic acid complexes, milk thistle, or frankincense have so far been primarily investigated in laboratory and animal studies. Here, controlled human studies are lacking to confirm effects on energy metabolism.

Many of the substances studied share similar mechanisms of action, such as the modulation of inflammatory processes, antioxidant effects, or the activation of signalling pathways like SIRT1 or Nrf2. These commonalities suggest that combinations or synergistic effects may be possible. For instance, humic acid complexes, which exhibit antioxidant and anti-inflammatory properties in laboratory settings, could potentially produce effects similar to those of established substances. However, systematic human studies are lacking to validate such extrapolations.

4. Key Human Studies

• 1 Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomised controlled pilot study (2023) — Coenzyme Q10
• 2 Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomised Controlled Trials (2022) — Coenzyme Q10
• 3 Coenzyme Q10 Supplementation in Statin-Treated Patients: A Double-Blinded Randomised Placebo-Controlled Trial (2022) — Coenzyme Q10
• 4 Mechanisms underlying the anti-wasting effect of L-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies (2013) — L-Carnitine
• 5 Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral nervous system and beyond (2013) — L-Carnitine
• 6 The effects of concurrent Coenzyme Q10 and L-carnitine supplementation in migraine prophylaxis: A randomised, placebo-controlled, double-blind trial (2019) — L-Carnitine
• 7 Anti-Inflammatory Diet and Probiotic Supplementation as Strategies to Modulate Immune Dysregulation in Autism Spectrum Disorder (2025) — Chronic Inflammation
• 8 Coenzyme Q10 and Intracellular Signalling Pathways: Clinical Relevance (2025) — Chronic Inflammation
• 9 Quercetin activates the SIRT6-Nrf2 axis during oxidative stress, modulating ageing-associated markers in healthy men (2025) — Chronic Inflammation
• 10 Effects of Kefir Consumption on Gut Microbiota and Athletic Performance in Professional Female Soccer Players: A Randomised Controlled Trial (2025) — Gut Microbiome
• 11 Can Probiotics Influence Adaptive Thermogenesis Induced by Continuous Energy Restriction after a 12-Week Intervention in Adult Males Living with Obesity? (2025) — Gut Microbiome
• 12 Multi-Axis Reprogramming of Muscle-Metabolic Crosstalk by HiLo Platinum™ Restores Strength in Prediabetes via Mitochondrial Activation and Gut Microbiome (2026) — Gut Microbiome
• 13 High-dose resveratrol supplementation in obese men: an investigator-initiated, randomised, placebo-controlled clinical trial of substrate metabolism (2013) — Resveratrol
• 14 Serum concentrations and gene expression of sirtuin 1 in healthy and mildly overweight individuals after caloric restriction or resveratrol supplementation (2017) — Resveratrol
• 15 Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first-degree relatives of patients (2018) — Resveratrol
• 16 Melatonin as a potential therapy for sepsis: a phase I dose-escalation study and an ex vivo whole blood model under sepsis conditions (2014) — Melatonin
• 17 Therapeutic potential of melatonin and its analogues in Parkinson’s disease: focus on sleep and neuroprotection (2011) — Melatonin
• 18 Melatonin supplementation for six weeks had no effect on arterial stiffness and mitochondrial DNA in women aged 55 years and older with insomnia: a double-blind, randomised, placebo-controlled trial (2021) — Melatonin
• 19 Curcumin as a therapeutic agent for sarcopenia (2023) — Turmeric and curcumin
• 20 Effect of turmeric supplementation on blood pressure and serum levels of sirtuin 1 and adiponectin in patients with non-alcoholic fatty liver disease: a randomised controlled trial (2022) — Turmeric and curcumin
• 21 Potential adjunctive effects of quercetin–curcumin co-supplementation in adults with mild-to-moderate long COVID: results from a pragmatic exploratory study (2026) — Turmeric and curcumin
• 22 The immune cell transcriptome is modulated by vitamin D₃ supplementation in individuals with a first demyelinating event participating in a clinical trial (2024) — Vitamin D
• 23 Consensus statement on the role of vitamin D in metabolic health (2026) — Vitamin D
• 24 Vitamin D and resveratrol in sarcopenic obesity: a systematic review highlighting the gap in phenotype-defined randomised controlled trials (2026) — Vitamin D

5. Open Questions

• Humic acid complexes: Are there dose-dependent effects on mitochondrial markers in controlled studies?
• Combination therapies: Can synergistic effects of substances such as coenzyme Q10 and L-carnitine be demonstrated in long-term studies?
• Chronic inflammation: How do different inflammation modulators affect mitochondrial biogenesis in various patient groups?
• Gut microbiome: Which specific microorganisms or metabolites directly influence mitochondrial function?
• Subjective fatigue: Can biomarkers be identified to enable objective measurement of fatigue associated with mitochondrial dysfunction?

See also the gap list covering all substances. This page is recalculated with each update.