How Magnesium Affects Oxidative Stress and Antioxidant Enzymes

Magnesium status influences oxidative stress mainly by changing how many reactive oxygen species (ROS) are produced and how well key antioxidant enzymes function. Deficiency tends to increase oxidative damage and weaken antioxidant defenses, whereas adequate magnesium generally supports mitochondrial function, redox balance, and some antioxidant systems.

How deficiency increases oxidative stress

Low magnesium (Mg deficiency) is repeatedly linked with higher markers of oxidative damage to lipids, proteins, and DNA in cells and animals. Several interconnected mechanisms are involved:

• Increased catecholamines and activation of the renin–angiotensin system promote ROS production and inflammation, amplifying oxidative stress.​
• Disturbed calcium–magnesium balance and mitochondrial dysfunction uncouple oxidative phosphorylation, causing electron leakage in the respiratory chain and excess ROS generation.​

Effects on mitochondria and cellular energy

Magnesium is essential for ATP binding and for maintaining mitochondrial membrane potential (MMP). Under oxidative stress (for example with hydrogen peroxide), rising free Mg²⁺ helps preserve MMP, reduce mitochondrial damage, and attenuate cell death in experimental models.​
Adequate Mg²⁺ supports tricarboxylic acid (TCA) cycle activity and helps prevent opening of the mitochondrial permeability transition pore, both of which limit ROS-driven mitochondrial injury.​

Modulation of antioxidant enzymes

Magnesium deficiency is associated with a “weakened antioxidant defence,” including changes in glutathione (GSH) and enzymes that use it. In animal and cell studies, Mg deficiency has been linked to:​

• Reduced GSH levels and altered glutathione-related enzymes, making cells more vulnerable to peroxidation.​
• Impaired stability or activity of antioxidant enzymes such as superoxide dismutase (SOD), with some work highlighting magnesium’s role in stabilizing SOD structure and function in neural tissue.​

Evidence from supplementation studies

Experimental and early human data suggest potential protective effects of magnesium, but findings for direct antioxidant effects are mixed.​

• In one study, four weeks of magnesium supplementation reduced DNA damage in blood lymphocytes exposed to hydrogen peroxide in both athletes and sedentary young men, indicating improved resistance to oxidative insult.​
• A recent systematic review reported consistent anti‑inflammatory effects (e.g., lower C‑reactive protein) but no clear, uniform reduction in standard oxidative stress biomarkers such as malondialdehyde or total antioxidant capacity across trials.​

Practical implications

Overall, magnesium is not a classic free‑radical scavenger like vitamin C, but rather a cofactor and regulator that helps keep ROS production under control and supports antioxidant enzyme systems. Maintaining adequate dietary magnesium—rather than relying on high‑dose supplements in isolation—appears most important for protecting mitochondrial function, preserving antioxidant capacity, and limiting chronic oxidative stress.​

James Eckburg

REDOX HEALTH