As global aging accelerates, the burden of Alzheimer’s disease (AD) and related dementias is rising at an alarming pace, profoundly impacting families and healthcare systems worldwide. Recent findings suggest that metabolic interventions using niacin (vitamin B3) and epigallocatechin gallate (EGCG), a major antioxidant in green tea, may restore guanosine triphosphate (GTP) levels in aging neurons. By improving autophagy, reducing protein aggregation, and mitigating oxidative stress, these compounds demonstrate promising neuroprotective potential. This article explores the hidden role of GTP depletion in neurodegeneration, the dual therapeutic mechanism of niacin and EGCG, and the broader implications of B vitamins and green tea in supporting cognitive health and cardiovascular well-being.
When Memories Begin to Fade
Imagine you're talking to a loved one at home, only to find their eyes gradually becoming confused and blank, unable to recognize the familiar face before them. This scene is not uncommon today; it's a reality faced by countless families. The accelerating aging of the population has made "memory loss" no longer just a literary metaphor but a real crisis. Alzheimer's disease (AD) has become one of the most common neurodegenerative diseases, affecting millions worldwide and silently eroding cognition, family bonds, and self-identity.
The "China Alzheimer's Disease Report 2024" indicates that as of 2021, the number of people living with AD and other dementias in China has reached 16.99 million, with a prevalence of 1,194.2 cases per 100,000 people and a mortality rate of 34.6 per 100,000. Behind these cold statistics lie countless fading memories and family bonds.
Yet researchers are working within the fragile gaps of time to discover new “memory repair agents.” A recent study published in GeroScience [2] revealed that treating aging neurons with niacin (vitamin B3) or EGCG (a green tea antioxidant catechin) for just 16 hours significantly elevated guanosine triphosphate (GTP) energy levels to near youthful states. Even more strikingly, the combined treatment fully restored GTP to youthful levels. This metabolic intervention not only repaired vesicle transport and autophagy function but also markedly reduced Aβ aggregation and oxidative protein damage, opening a potential new path for slowing neuronal aging and combating AD.
DO1:10.1007/s11357-025-01786-4
GTP Depletion: The Hidden Energy “Famine” in Aging Neurons
As age advances, neurons begin to show signs of “energy bankruptcy.” While ATP is the more familiar “currency” fueling ion balance and synaptic transmission, GTP represents an equally vital “checkbook” in the energy ledger. GTP plays the role of a molecular switch in signaling pathways and is indispensable in maintaining protein homeostasis, particularly in autophagy and vesicular trafficking.
To trace the fate of this crucial energy source, researchers studied hippocampal neurons from aged 3xTg-AD transgenic mice (a classic Alzheimer’s model). Using a novel fluorescent probe (GEVAL), they monitored free GTP and bound GTP in living cells. The results were striking: the ratio of free to bound GTP declined significantly with age, pointing directly to a state of GTP scarcity in aging neurons.
Further subcellular localization revealed that free GTP within mitochondria—its primary production site—was markedly reduced. This suggested that mitochondrial metabolism and GTP synthesis capacity were diminished in aging neurons as well as in those with AD genotypes. Meanwhile, abnormal vesicle-like structures enriched in GTP began to accumulate in the cytoplasm, indicating impaired vesicle handling and waste clearance.
Figure: Aging and AD genotype-associated reduction of free GTP in hippocampal neurons
Two small GTPases—Rab7 and Arl8b—play pivotal roles in protein clearance via autophagy. In 3xTg-AD neurons, Rab7 and Arl8b accumulated significantly within axons and dendrites. This revealed impaired fusion of endosomes with lysosomes, leading to vesicle buildup and pathological protein aggregation.
Dual Strategy: Energy Supply Meets Oxidative Defense
How can neurons overcome this energy crisis? It is well established that mitochondrial function declines with age, impairing both energy production and antioxidant defense. Past studies have shown that aging neurons exhibit reduced capacity to sustain mitochondrial free NADH, leading to energy deficits and “power shortages” inside the cell.
The research team devised a clever two-pronged approach. First, they supplemented with niacin (vitamin B3), a precursor of NAD+, to boost glycolysis and the tricarboxylic acid (TCA) cycle—two critical “power plants” of the cell—thereby enhancing GTP synthesis and mitochondrial metabolism. However, increasing mitochondrial activity can inadvertently raise oxidative stress by generating more reactive oxygen species (ROS).
To counteract this, the team introduced EGCG, the celebrated green tea catechin and a natural Nrf2 pathway activator. EGCG functions like a cellular “shield,” stimulating antioxidant defenses and reducing oxidative injury.
After just 16 hours of this combined “fueling and shielding” therapy, results were compelling: both niacin and EGCG alone raised GTP levels in aged neurons to near-youthful levels, while their combination fully restored GTP to youthful status.
In short, the study demonstrated that pairing niacin with EGCG rapidly restores GTP levels, enhances autophagy, clears Aβ protein aggregates, and lowers oxidative protein damage in aging neurons.
Figure: Treatment with energy precursors and Nrf2 inducers restores GTP levels and vesicle size in aged neurons
B Vitamins: Unlocking the Brain’s Protective Code
Beyond this dual therapy, vitamins and green tea stand strong individually as brain protectors.
A study by a Shanghai research team, published in Nutrients [3], evaluated the effects of vitamin supplementation on preventing cognitive decline. Among 892 adults over age 50, participants were grouped into normal controls (NC, n=185), subjective cognitive decline (SCD, n=227), mild cognitive impairment (MCI, n=296), and Alzheimer’s disease (AD, n=184). Results showed that daily supplementation with folate, B vitamins, vitamin D, and coenzyme Q10 significantly delayed cognitive decline and neurodegeneration.
Focusing on B vitamins, even occasional use reduced the risk of developing cognitive impairment by approximately 36.1%. Daily supplementation pushed this risk reduction to about 60.9%.
But why are B vitamins so effective? The “B family” includes thiamine, riboflavin, niacin, pantothenic acid, vitamin B6, folate, biotin, and vitamin B12. Prospective studies suggest that sufficient intake of folate, B6, and B12 is linked to stronger cognitive reserves. Mechanisms may involve higher methylation of oxidative stress-related genes (NUDT15 and TXNRD1) and reduced oxidative damage. Still, the precise effects of each B vitamin on different populations require more detailed research.
Green Tea: More Than Brain Protection
The benefits of green tea extend beyond neuroprotection. In addition to shielding neurons from aging-related decline, green tea also shows significant blood pressure-lowering effects.
A systematic review and meta-analysis published in Blood Pressure [4] included 36 randomized controlled trials and strictly adhered to PRISMA guidelines. Findings revealed that green tea supplementation reduced systolic blood pressure (SBP) by about 1.08 mmHg and diastolic blood pressure (DBP) by about 1.09 mmHg.
Subgroup analysis revealed that reductions in SBP were especially pronounced in individuals with baseline SBP >120 mmHg, women, participants under age 45, individuals with BMI <30 kg/m², intervention durations <8 weeks, daily intake <500 mg, and in trials involving brewed green tea. For DBP, improvements were observed across most subgroups, although not significant in studies involving participants with baseline DBP <80 mmHg, interventions >8 weeks, healthy individuals, or exclusively male cohorts.
Conclusion
The convergence of nutrition and neuroscience is painting an exciting new picture of brain health. By restoring neuronal GTP levels, niacin and EGCG may unlock new therapeutic avenues for Alzheimer’s disease. Meanwhile, consistent intake of B vitamins and green tea not only supports cognitive resilience but also enhances cardiovascular health.
As the world faces a growing wave of aging and dementia, these findings offer more than just numbers—they offer hope. Hope for families witnessing memory loss, hope for researchers pushing the boundaries of intervention, and hope that through simple yet powerful nutrients, we may one day rewrite the story of aging brains.
References
- Wang, G., Qi, J., Liu, X., et al. (2024). China Alzheimer Report 2024. Journal of Diagnostic Concepts and Practice, 23(3), 219-257.
- Santana RA, McWhirt JM, Brewer GJ. Treatment of age-related decreases in GTP levels restores endocytosis and autophagy. GeroScience. 2025 Aug 2. doi: 10.1007/s11357-025-01786-4. Epub ahead of print. PMID: 40751793.
- Jiang X, Guo Y, Cui L, Huang L, Guo Q, Huang G. Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability. Nutrients. 2023 Mar 1;15(5):1243. doi: 10.3390/nu15051243. PMID: 36904242; PMCID: PMC10005055.
- Rezaei M, Akhavan N, Fathi F, Alavi SM, Fadaii M, Dehzad MJ, Askarpour M. Effect of green tea supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Blood Press. 2025 Dec;34(1):2517122. doi: 10.1080/08037051.2025.2517122. Epub 2025 Jun 12. PMID: 40497293.
- EFSA ANS Panel (2018). Scientific Opinion on the safety of green tea catechins. EFSA Journal, 16(4), 5239. https://doi.org/10.2903/j.efsa.2018.5239