Cellular life depends on a delicate balance between the production of reactive molecules and the body's ability to neutralize them. During normal processes such as cellular respiration, by which we produce energy in the mitochondria, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated.

These molecules, commonly known as "free radicals," fulfill important physiological functions in cell signaling and immunity. However, when they are produced in excess or when antioxidant defenses are insufficient, they can damage lipids, proteins, and DNA, leading to what is known as oxidative stress.

Oxidative stress is linked to biological aging and the development of cardiovascular, metabolic, neurodegenerative, and inflammatory diseases. To counteract it, the body has a highly sophisticated antioxidant system.

This system includes endogenous defenses, which are produced by the body itself, such as specialized enzymes. Among these are: superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx).

In addition to these internal defenses, we rely on exogenous antioxidants, meaning those we obtain through diet or supplementation. Within this group, compounds such as astaxanthin, vitamin E, and selenium stand out, as their mechanisms of action have been widely studied.

Beyond "neutralizing free radicals," these nutrients participate in the regulation of complex cellular pathways that control inflammation, immune response, energy metabolism, and cell survival.

Astaxanthin is a fat-soluble, red-orange carotenoid found in microalgae such as Haematococcus pluvialis, as well as in crustaceans and some fish. Its chemical structure contains additional oxygenated groups that allow it to insert itself through the cell membrane and stabilize it, which explains its high antioxidant capacity compared to other carotenoids.

At the molecular level, astaxanthin neutralizes ROS and RNS and protects against lipid peroxidation, a process by which free radicals damage the fatty acids in cell membranes.

It also modulates key regulatory pathways:

1. It activates Nrf2, a transcription factor that stimulates the production of internal antioxidant enzymes. In simple terms, it helps the body to "turn on" its own defense systems.
2. It inhibits NF-κB, a protein that regulates the expression of inflammatory genes such as iNOS and COX-2, thereby reducing excessive inflammatory response.

Various systematic reviews and meta-analyses have shown that astaxanthin supplementation can reduce oxidative stress biomarkers such as malondialdehyde (MDA), decrease C-reactive protein (CRP) in certain contexts, and improve some lipid profile parameters, including a moderate increase in HDL.

It has also been observed in some clinical trials that in people with type 2 diabetes, there was a reduction in IL-6 (a key cytokine in systemic inflammation, rheumatoid arthritis, and autoimmune diseases).

• Cardiovascular health: The oxidation of LDL lipoproteins is a key step in the development of atherosclerosis. Clinical studies have shown that astaxanthin supplementation can reduce LDL oxidation, decrease triglycerides in some individuals, and slightly increase HDL in certain contexts. These effects are related to its ability to neutralize reactive oxygen species, protect the vascular endothelium, and modulate inflammatory pathways involved in arterial damage.

• Inflammatory modulation: Low-grade chronic inflammation is implicated in multiple metabolic diseases. Some clinical trials have shown that astaxanthin can decrease inflammatory markers such as C-reactive protein and certain pro-inflammatory interleukins. This effect is associated with the modulation of cellular pathways such as NF-κB and the reduction of mitochondrial oxidative stress, acting as a physiological regulator of inflammatory balance.

• Metabolic health: Oxidative stress plays an important role in insulin resistance and metabolic dysfunction. Clinical and experimental studies suggest that astaxanthin can improve parameters related to insulin sensitivity, reduce lipid accumulation in the liver, and protect pancreatic β-cells against oxidative damage, contributing to the maintenance of more efficient metabolism.

• Skin health: Clinical evidence exists showing improvements in skin elasticity, reduction of fine wrinkles, and a decrease in damage induced by UV radiation after astaxanthin supplementation. Its antioxidant action protects collagen and elastin against free radicals and reduces the activation of degrading enzymes induced by sun exposure, functioning as internal support but not as a substitute for sunscreen.

• Cognitive function: Preliminary research suggests that astaxanthin can cross the blood-brain barrier and exert neuroprotective effects by reducing cerebral oxidative stress. Some small studies have observed improvements in memory parameters and mental fatigue, although more robust clinical trials are required to confirm these findings.

Vitamin E is not a single molecule, but a family composed of eight natural forms: four tocopherols and four tocotrienols. α-tocopherol is the predominant form in human tissues and the most widely used in supplementation.

It is the primary fat-soluble "chain-breaking" antioxidant, which means it interrupts the chain reaction of lipid peroxidation. When a free radical attacks a polyunsaturated fatty acid (PUFA) of the cell membrane, a cascade reaction begins. Vitamin E donates an electron to stop that reaction and protect the structural integrity of the membrane.

After donating that electron, vitamin E becomes a relatively stable radical (tocopheroxyl radical), which can be regenerated by other antioxidants such as vitamin C. This networked work is characteristic of the biological antioxidant system.

In addition to its antioxidant function, vitamin E modulates immunological and inflammatory processes, influences the function of T-cells (white blood cells essential to the immune system that protect the body against viral and bacterial infections), and participates in the regulation of enzymes associated with vascular function.

Recent meta-analyses have shown that supplementation can decrease LDL oxidation and increase the lag time before LDL becomes oxidized, particularly in younger people and with moderate doses (≤400 IU/day). However, as noted by reviews in Nature Reviews Drug Discovery, the clinical efficacy of antioxidants depends on the context, dose, and state of each individual.

• Protection of cell membranes: Vitamin E is a fat-soluble antioxidant that integrates into the lipid bilayer of cell membranes and protects polyunsaturated fatty acids against lipid peroxidation. It acts by interrupting free radical chain reactions, being an essential component of the antioxidant system along with vitamin C and glutathione.

• Immune support: In older adults, some clinical trials have shown that adequate supplementation can improve T-cell function and support the cellular immune response. This effect is particularly relevant during aging, a stage in which oxidative stress increases and immune efficiency can decline.

• Neurological health: Vitamin E is essential for the integrity of nervous tissue due to its protective role against lipid oxidation in neurons. Deficiency can lead to peripheral neuropathy, motor impairment, and progressive neurological deterioration, confirming its critical role in the health of the nervous system.

• Potential angioprotective effect: Some studies suggest that vitamin E may contribute to improving endothelial function and reducing LDL oxidation, processes involved in the development of atherosclerosis.

Selenium is an essential trace element incorporated in the form of selenocysteine within specialized proteins called selenoproteins. At least 25 selenoproteins have been identified in humans.

Among the most important are:

1. Glutathione peroxidases (GPx): enzymes that neutralize peroxides and protect cell membranes.
2. Thioredoxin reductases (TrxR): participate in the regulation of cellular redox balance.
3. Thyroid deiodinases (DIO): convert thyroid hormone T4 into its active form T3, regulating metabolism.

Selenium, therefore, does not act simply as a "direct antioxidant," but rather enables enzymes to function properly. Additionally, it influences pathways such as Nrf2 and NF-κB, modulates the immune response, and participates in processes related to inflammation and viral control.

Scientific literature and evidence have shown associations between adequate selenium levels and better immune function, thyroid health, and fertility.

• Immune function: Selenium is a component of antioxidant enzymes like glutathione peroxidase, which protect cells from oxidative damage during infectious processes. Adequate levels support lymphocyte proliferation, the activity of NK cells (lymphocytes that act as a first line of defense, responding rapidly to threats), and the balance of the cellular and humoral immune response.

• Thyroid health: The thyroid gland concentrates high amounts of selenium due to its involvement in deiodinase enzymes responsible for converting T4 into T3, the active form of thyroid hormone. Furthermore, it helps protect thyroid tissue against the oxidative stress generated during hormonal synthesis, which is particularly relevant in contexts of mild autoimmunity.

• Cardiovascular health: Observational studies have found associations between adequate selenium levels and a lower coronary risk due to its role in vascular antioxidant defense. However, scientific evidence indicates that an appropriate balance must be maintained, as both low and excessive levels of selenium have been associated with increased cardiometabolic risk, whereas concentrations within an optimal range appear to offer the greatest benefit.

• Fertility: In men, selenium participates in the structural formation of sperm and in sperm motility, showing improvements in cases of deficiency. In women, it is involved in early embryonic development and in proper thyroid functioning during pregnancy.

• Cognitive function: Population studies have observed that adequate selenium levels are associated with better cognitive performance in older adults, possibly due to its role in neuronal antioxidant protection.

Nutrients such as astaxanthin, vitamin E, and selenium do not act in isolation; they are part of an integrated biological network that protects membranes, regulates inflammation, participates in the immune response, and supports essential metabolic functions.

Scientific evidence supports their role in the modulation of oxidative stress, although it also makes clear that the benefit depends on individual context, nutritional status, and dosage.

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