Not an Antioxidant but actually Oxidative Stress! New Research on Green Tea.

A recent study published in Aging has reached a groundbreaking conclusion: Catechins in green tea not only fail to suppress oxidative stress but instead promote oxidative stress in the short term. Researchers from the University of Jena in Germany, ETH Zurich in Switzerland, and Huazhong Agricultural University in China have made this paradigm-shifting discovery.

Previous clinical trials and epidemiological studies have shown that drinking green tea is beneficial to health, including lowering blood pressure, blood sugar, cholesterol levels, and aiding in weight loss. The most abundant polyphenolic compounds in green tea are epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), which together account for 70% of the total catechins in green tea. Studies conducted in various model organisms have shown that green tea catechins contribute to lifespan extension due to metabolic adaptation and enhanced resistance to reactive oxygen species (ROS).

However, the bioavailability of green tea catechins in mammals is relatively low, making it unlikely that humans can reach such concentrations through oral consumption. Despite this, several independent clinical trials have confirmed that drinking green tea can improve various physiological health markers. After consuming 4.5 grams of decaffeinated green tea extract, the maximum plasma concentration of EGCG, ECG, and epicatechin (EC) in humans reached 2.5 μM.

In this study, researchers examined whether a 2.5 μM concentration of EGCG and ECG was sufficient to promote lifespan extension in Caenorhabditis elegans (C. elegans) by inducing a mitotic response. The researchers found that EGCG and ECG at this concentration enhanced the physical fitness and lifespan of C. elegans. Moreover, this relatively low dose was sufficient to inhibit mitochondrial respiratory chain activity in the worms.

The two most abundant catechins in green tea can extend the lifespan of Caenorhabditis elegans.

Subsequently, experiments in isolated mouse liver mitochondria showed that EGCG and ECG inhibited mitochondrial complex I activity. After six hours of EGCG administration and twelve hours of ECG administration, complex I inhibition was accompanied by a transient increase in ROS formation and a decrease in ATP levels.

The findings demonstrated that the lifespan-extending effects of EGCG and ECG in C. elegans depend on the presence of AMP-activated kinase (AAK-2) and NAD-dependent deacetylase SIR-2, both of which are crucial metabolic regulators. These data suggest that a transient drop in AMP levels leads to subsequent energy deficiency, activating the energy sensors AAK-2 and SIR-2.1 in C. elegans. Additionally, the temporary increase in ROS levels may enhance the activity of the mitogen-activated protein kinase homolog PMK-1, thereby promoting the corresponding signaling cascade. These signaling pathways stimulate adaptive responses by enhancing oxidative stress defenses, such as the increased activity of superoxide dismutase (SOD) and catalase (CTL), thereby improving oxidative stress resistance and promoting health and longevity.

Green tea catechins enhance fitness and lifespan of Caenorhabditis elegance by complex I inhibition

In summary, mitochondrial complex I inhibition has once again been demonstrated as a powerful tool for promoting lifespan extension.

Professor Michael Ristow, the corresponding author of the study and a researcher at ETH Zurich’s Institute of Health Sciences and Technology, stated: "This means that green tea catechins are not actually antioxidants but rather pro-oxidants that stimulate the body’s self-defense mechanisms, similar to how vaccines work." Ristow was not surprised by this mechanism. His research team had already demonstrated in 2009 that exercise promotes health by transiently increasing oxidative stress, which in turn enhances the body’s defense mechanisms. Similarly, caloric restriction has repeatedly been shown in animal studies to extend lifespan—mice fed a low-calorie diet live longer than those consuming a normal high-calorie diet.

Ristow explained: "So it makes sense that catechins in green tea work in a similar way. This is logical to me." He further noted that these findings also apply to humans, as the fundamental biochemical process of neutralizing reactive oxygen species (ROS) has been evolutionarily conserved across species, from single-celled yeast to humans.

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