A green tea extract and vitamin B3 combo may hold the key to reviving the brain’s natural cleanup crew, restoring energy, clearing toxic Alzheimer’s proteins, and giving aging neurons a second wind, according to new research.
Although the largest risk factor for Alzheimer’s disease is age, the age-related mechanisms that contribute to that risk aren’t clear. While some propose that a buildup of toxic amyloid-beta proteins is to blame, others say the condition is caused by an imbalance in cellular energy supply and demand.
A new study by researchers from the University of California, Irvine has found that a combination of two natural compounds, readily available as dietary supplements, helps revive the brain’s natural cleanup system that removes damaged parts and toxic buildup.
“As people age, their brains show a decline in neuronal energy levels, which limits the ability to remove unwanted proteins and damaged components,” said the study’s lead author, Gregory Brewer, adjunct professor of biomedical engineering at UC Irvine. “We found that restoring energy levels helps neurons regain this critical cleanup function.”
Studying neurons from young, middle-aged, and old mice, including a special Alzheimer’s disease (AD) model, the researchers used a fluorescent sensor to directly measure guanosine triphosphate, or GTP. This high-energy molecule drives key cellular processes such as endocytosis (bringing substances into cells) and autophagy (clearing cellular waste). Think of it like the fuel that powers the cell’s garbage disposal system. Without it, waste builds up, especially in aging or diseased brains.
They tested the effects of two natural compounds: nicotinamide, a water-soluble form of vitamin B3, and epigallocatechin gallate (EGCG), the most abundant polyphenol, a category of plant-based compounds, found in green tea. The researchers evaluated GTP levels and location within cells, activation of autophagy-related pathways, accumulation of amyloid-beta protein and oxidative damage, and neuron survival. They found that free GTP was highest in middle-aged normal mice but dropped significantly in old mice and even earlier in AD-model mice. GTP reduction was linked to a decline in the mitochondria, the cell’s energy-producing machinery, particularly in AD-model neurons.
Autophagy requires GTP to power it. When a drug was used to block autophagy, free GTP increased (it wasn’t being used); when the process was stimulated using a different drug, GTP decreased, showing that it was being consumed. In AD-model neurons, stimulating autophagy had little effect on GTP, suggesting the neurons were already maxed out.
When neurons from old mice were treated in the lab with a combination of nicotinamide and EGCG, GTP levels were restored to youthful levels in older neurons, notably after only 16 hours of treatment. The number and size of GTP-labelled vesicles, fluid-filled sacs that accumulate when waste isn’t cleared, also returned to youthful norms. The treatment also activated Nrf2, a protein that regulates antioxidant genes, reduced amyloid-beta aggregates, decreased a marker of oxidative stress, and improved cell survival by 22%.
“This study highlights GTP as a previously underappreciated source driving vital brain functions,” Brewer said. “By supplementing the brain’s energy systems with compounds that are already available as dietary supplements, we may have a new path toward treating age-related cognitive decline and Alzheimer’s disease.”
The study has some limitations. Experiments were undertaken using lab-grown neurons, not in live animals. The AD-model mice overproduce amyloid proteins, which may not fully reflect human Alzheimer’s disease. The effects were observed after 16 hours, but long-term outcomes are unknown. And the study didn’t assess whether the treatment affected memory or learning.
Nonetheless, the study has real-world implications. Primarily, it identifies GTP depletion as a key aging and AD-related factor that disrupts normal cellular cleanup processes. Further, nicotinamide combined with EGCG shows promise as a low-risk, rapid-acting treatment to rejuvenate energy metabolism, reduce neurotoxic waste, and restore neuron function. It could lead to new dietary or pharmaceutical interventions for aging and Alzheimer’s that work by targeting cellular energy balance, not just amyloid plaques.
The study was published in the journal GeroScience.
Source: UC Irvine
