Nicotinamide, EGCG Combination May Promote Natural Brain Cleaning: In Vivo Study  

A combination of two bioactive compounds, nicotinamide and a green tea antioxidant called epigallocatechin gallate, appeared to rejuvenate aging brain cells and clear away the buildup of harmful proteins associated with Alzheimer’s disease, according to a new in vivo study conducted by researchers at UC Irvine. The findings were published in GeroScience.

The paper looked at a combination of naturally-occurring compounds – a form of vitamin B3 called nicotinamide and a green tea antioxidant called epigallocatechin gallate (ECG) – can reinstate levels of guanosine triphosphate, an essential energy molecule in brain cells.

In neurons, treatment reversed age-related cellular deficits and improved brain cells’ ability to clear amyloid protein aggregates, which are associated with Alzheimer’s disease.

“As people age, their brains show a decline in neuronal energy levels, which limits the ability to remove unwanted proteins and damaged components,” said 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.”

The researchers used an encoded fluorescent sensor called GEVAL to track guanosine triphosphate GTP levels in neurons from aged Alzheimer’s model mice. GTP levels declined with age, particularly in the mitochondria, leading to impaired autophagy (the process by which cells clear damaged components).

A 24-hour of treatment with nicotinamide and EGCG restored GTP levels to those seen in younger cells. This revival led to improved energy metabolism; activation of key GTPases involved in cellular trafficking, Rab7 and Arl8b; and efficient clearance of amyloid beta aggregates. Oxidative stress was also reduced.

“This study highlights GTP as a previously underappreciated energy 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.”

“More work is going to be required to find the best way to administer this treatment, since a recent clinical trial involving UC Irvine researchers showed that oral nicotinamide was not very effective because of inactivation in the bloodstream.”