Oxidative Stress, Mitochondria, and Energy

1. Free Radicals: Signal and Damage in One

Humic acid complexes significantly reduce malondialdehyde (MDA), a marker of lipid peroxidation (p=0.049) 2.

Plausible Reactive oxygen species (ROS) are not merely harmful but also serve as signalling molecules—for instance, in vascular regulation or immune response. Astaxanthin exhibits a 100–500-fold higher oxygen radical absorbance capacity (ORAC) than α-tocopherol 4, suggesting superior radical neutralisation. CoQ10 also protects against glutamate-induced excitotoxicity, a key mechanism in neurodegenerative diseases 1.

Hypothesis If ROS have both signalling and damaging functions, indiscriminate “antioxidant” supplementation may be counterproductive in certain contexts (e.g., during training or immune defence). The observed MDA reduction by humic acid complexes 2 suggests that these compounds not only scavenge radicals but may also modulate ROS production at the source (e.g., mitochondria).

Compounds at this node: Astaxanthin · Coenzyme Q10 · Quercetin · Humic acid complexes

2. Endogenous Defence: Nrf2, Glutathione, SOD

Evidence-based: Sulforaphane from broccoli induces phase II enzymes such as GSTM1, which degrade ROS 5.

Plausible Nrf2 is the central transcription factor for antioxidant enzymes. While sulforaphane activates Nrf2 in healthy cells 5, it shows no effect in COPD patients 6—potentially due to chronic inflammatory blockades. Hydroxytyrosol also improves the ratio of oxidised to reduced glutathione 7, indicating direct redox modulation.

Compounds at this node: Sulforaphane (broccoli) · Green tea and EGCG · Olive polyphenols (hydroxytyrosol) · Black cumin (Nigella sativa)

3. Mitochondria: Q10, Carnitine, Creatine

Evidence-based: CoQ10 preserves mitochondrial bioenergetics and reduces ROS-induced DNA damage in oocytes 3. L-carnitine improves liver function in non-alcoholic steatohepatitis 9 and lowers MDA in coronary patients 13.

Plausible Creatine not only acts as an energy store (phosphocreatine) but also stabilises mitochondrial membrane potential oscillations triggered by ROS 12. L-carnitine facilitates fatty acid transport into mitochondria, thereby reducing lipid peroxidation 13. The combination of CoQ10, creatine, and carnitine (the “mitochondrial cocktail”) demonstrates synergistic effects in mitochondrial disorders 10.

Hypothesis The observed effects of CoQ10 on oocyte quality 3 and creatine on cognitive performance 11 suggest that mitochondrial optimisation enhances not only energy provision but also cellular resilience. A targeted combination of these compounds may be particularly effective in neurodegenerative diseases (e.g., Parkinson’s 8) or fatigue syndromes.

Compounds at this node: Coenzyme Q10 · L-carnitine · Creatine · Spermidine

4. Measurable Outcomes: Biomarkers, Performance, Fatigue

Resveratrol also modulates SIRT1, a regulator of mitochondrial biogenesis 14, underscoring the link between redox status and energy metabolism.

Humic acid complexes may act similarly: their MDA-lowering effect 2 suggests potential for reducing fatigue, though this has not yet been directly measured.

Compounds at this node: Coenzyme Q10 · Astaxanthin · L-carnitine · Resveratrol

Implications and Open Questions

Hypothesis This chain demonstrates that “antioxidant” activity in the body is a multidimensional process: it is not merely about scavenging radicals but also about modulating signalling pathways (Nrf2), stabilising mitochondria (CoQ10, carnitine), and reducing inflammation-driven ROS sources (black cumin, olive polyphenols). The observed effects on fatigue, cognitive performance, and inflammatory markers suggest that these compounds act synergistically—for example, by simultaneously reducing ROS production (e.g., via CoQ10 1) and strengthening endogenous defence (e.g., via sulforaphane 5). Particularly relevant appears the combination of compounds targeting different mechanisms: e.g., humic acid complexes (MDA reduction 2) with mitochondrial optimisers such as carnitine or creatine. The data imply that such combinations may be more effective in chronic diseases (e.g., diabetes, neurodegeneration) than single compounds, as they address both the cause (oxidative stress) and the consequence (mitochondrial dysfunction).

To investigate: A study should determine whether combining humic acid complexes with mitochondrial compounds (e.g., CoQ10 + L-carnitine) reduces fatigue in chronic conditions (e.g., Long COVID, cancer) more effectively than single compounds. Additionally, it should be examined whether Nrf2 activatability can be restored in COPD patients through anti-inflammatory compounds (e.g., black cumin). Finally, it would be worth investigating whether the observed effects on cognitive performance 11 and oocyte quality 3 stem from a shared mitochondrial stabilisation—and whether this can be further optimised through targeted combinations (e.g., creatine + CoQ10).

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