Green tea compound shows promise in protecting the brain from obesity-related damage

Obesity can damage a brain region involved in memory and learning, but a compound found in green tea might offer a way to protect it. A new study combining human dietary data and animal experiments found that an active ingredient in green tea helps preserve brain volume and memory by reducing inflammation and promoting cellular cleanup. The findings were published in the journal npj Science of Food.

Obesity is a widespread health condition that increases the risk of cognitive decline and dementia. One of the early signs of this mental decline is the shrinking of the hippocampus, a brain structure responsible for forming and storing memories. High amounts of body fat can cause chronic, low-level inflammation and insulin resistance throughout the whole body.

Insulin resistance occurs when cells stop responding properly to the hormone insulin, which normally helps them take in sugar for energy. In the brain, insulin does much more than just manage energy. It helps brain cells survive and adapt, while also controlling a process called autophagy. Autophagy is a biological recycling system that removes damaged cell parts and harmful protein clumps.

When obesity disrupts insulin signaling in the brain, it halts this internal recycling process. The resulting buildup of cellular waste damages the physical connections between brain cells. This structural damage ultimately leads to memory loss and reduced cognitive performance.

Researchers led by Xiaojun Wu, Qi Xu, and Zhiwei Ma at the Shanghai University of Traditional Chinese Medicine and ShanghaiTech University wanted to know if green tea could prevent this brain damage. Green tea contains high levels of epigallocatechin-3-gallate, or EGCG. This chemical compound is known to reduce inflammation and can mimic the health benefits of fasting or restricting calories. Fasting is a well-known trigger for the body’s cellular recycling system, making EGCG a promising candidate for restarting autophagy in the brain.

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The research team first looked for a link between green tea consumption and brain volume in humans. They analyzed brain scans and dietary surveys from 18,325 adults in the UK Biobank, which qualifies as a large study. The researchers divided the participants based on their body mass index and how much green tea they drank daily. They then measured the size of each person’s hippocampus using magnetic resonance imaging, or MRI.

The researchers found that obese individuals who drank no green tea had smaller hippocampi compared to people with normal body weights. When looking only at the obese participants, the researchers observed a linear trend suggesting that those who drank more green tea tended to have larger hippocampi. While this specific trend was not statistically significant, advanced statistical resampling confirmed that the direction of the relationship remained highly consistent across the population. This suggested a dose-dependent relationship, where more tea correlated with more brain volume.

To test whether EGCG directly protects the brain, the researchers conducted a small study using mice. They fed one group of male mice a standard diet and another group a high-fat diet for eight weeks to induce obesity. After eight weeks, they divided the obese mice into two separate groups. One group continued eating the high-fat diet alone, while the other group ate the high-fat diet but also received a daily oral dose of EGCG for four weeks.

The high-fat diet caused the untreated mice to gain weight and develop severe insulin resistance. After four weeks of treatment, the mice receiving EGCG had lower body weights compared to the untreated obese mice. The treated mice also showed much better insulin sensitivity. They were able to process sugars much more efficiently than their untreated counterparts.

The researchers then used MRI to scan the animals’ brains. The untreated obese mice showed a distinct loss of volume specifically in the hippocampus. The rest of their brain volume remained largely unchanged, highlighting the vulnerability of the memory center. In contrast, the mice treated with EGCG maintained normal hippocampal volume, matching the brain size of the healthy mice on the standard diet.

The researchers also tested the animals’ memory by having them navigate mazes and interact with new objects. The untreated obese mice struggled to recognize new objects and navigate a Y-shaped maze, indicating noticeable spatial memory problems. The EGCG-treated mice performed just as well as the healthy mice, showing that the physical brain preservation translated into actual cognitive benefits.

Finally, the researchers examined the brain tissue to understand exactly how EGCG worked. In the untreated obese mice, they found high levels of inflammatory proteins, broken insulin signaling, and stalled autophagy. The EGCG treatment completely reversed these issues in the brain cells. It quieted the inflammatory signals, restored the brain’s normal insulin response, and restarted the cellular recycling process.

By observing the tissue under an electron microscope, the scientists could physically see newly formed recycling structures inside the cells of the treated mice. The treated mice also had higher levels of a specific protein that keeps the physical connections between brain cells stable. This demonstrated that EGCG could protect the physical architecture of the brain from the stress of a high-fat diet.

The human portion of the research relied on observational data, meaning it cannot prove that green tea directly caused the larger brain volumes. The human participants also self-reported their tea intake, which can sometimes be inaccurate. In the animal experiments, the researchers only used male mice, which limits how the results might apply to females. The scientists also did not measure the exact amount of EGCG that reached the mouse brains.

This lack of measurement makes it hard to separate the compound’s direct effects on the brain from the general benefits of weight loss and improved body-wide metabolism. Future experiments will need to use chemical inhibitors to block autophagy during EGCG treatment to prove that the recycling process is entirely responsible for the benefits. Clinical trials in humans will also be necessary. These trials will need to administer controlled doses of EGCG to test its direct effects on brain structure and memory over time.

The study, “Green tea catechin EGCG attenuates hippocampal atrophy and cognitive impairment in obesity via autophagy signaling,” was authored by Kunyi Huang, Xin Li, Yujie Chen, Yiyun Qi, Weiying Zhang, Jia Ee Tan, Jia Ying Chan, Jiashuo Lu, Fangyi Hao, Jiayi Shi, Shuting Yan, Zhenzhen Huang, Xiaojun Wu, Qi Xu, and Zhiwei Ma.