Biochemical Society Transactions · 6 authors, 3 centres
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This review examines how carotenoids, particularly astaxanthin, can mitigate mitochondrial dysfunction by scavenging reactive oxygen species and modulating mitochondrial dynamics. It highlights that oxidative stress and mitochondrial dysfunction are early events in age-related diseases, and carotenoids may offer therapeutic potential. The paper underscores the need for better delivery systems and understanding of optimal dosing to translate these findings into clinical practice.
**Background:** Mitochondria are essential for ATP production, calcium homeostasis, and apoptosis, but they are also the primary source of reactive oxygen species (ROS). Excessive ROS lead to oxidative stress and mitochondrial dysfunction, which are implicated in age-related diseases such as Alzheimer's disease (AD), diabetes, and cardiovascular disorders. Carotenoids, lipophilic plant pigments with antioxidant properties, may protect mitochondria by scavenging free radicals and modulating signaling pathways. However, their role in mitochondrial health is not fully understood, and previous antioxidant trials have shown mixed results.
**Methods:** This is a narrative review that synthesizes findings from in vitro, animal, and human studies on carotenoids and mitochondrial function. The authors discuss the mechanisms of carotenoid absorption, metabolism (including the roles of β-carotene oxygenase 1 and 2), and their effects on mitochondrial dynamics, oxidative stress, and inflammation. Key carotenoids reviewed include lutein, zeaxanthin, lycopene, and astaxanthin.
**Key Results:** The review reports that carotenoids can reduce mitochondrial ROS production, inhibit mitochondrial fission (e.g., by decreasing Drp1 expression), and promote fusion and biogenesis. Astaxanthin is highlighted as the most potent mitochondrial-targeted antioxidant, with studies showing it improves mitochondrial activity and reduces oxidative damage. In AD patients, lower plasma levels of lutein, zeaxanthin, and lycopene were observed, and higher oxidized phospholipid levels correlated with cognitive decline. A 6-month carotenoid intervention did not change oxidized phospholipid levels in AD patients but increased them in controls. Lycopene restored mitochondrial respiratory activity after Aβ42 insult in rats. Astaxanthin, at doses up to 2.38 mg/day (EFSA recommendation), showed anti-inflammatory effects via COX2 and NF-κB inhibition. However, bioavailability remains a challenge, with plasma levels reaching only 39–52 nmol/L after supplementation.
**Clinical Implications:** The review suggests that carotenoids, especially astaxanthin, may be beneficial in preventing or delaying age-related diseases by improving mitochondrial function. However, clinical translation is limited by poor bioavailability, potential pro-oxidant effects under certain conditions, and the need for targeted delivery to mitochondria. Nanoencapsulation and liposomal formulations are promising strategies to enhance stability and uptake. The authors emphasize that personalized approaches and combination with lifestyle interventions (e.g., exercise) may optimize outcomes. Further research is needed to establish optimal doses, combinations, and delivery methods for carotenoids in mitochondrial dysfunction-related diseases.