Caffeine metabolite 1-MX boosts memory and brain health, study finds

A new study published in PLOS ONE suggests that a lesser-known metabolite of caffeine, called 1-methylxanthine (1-MX), may help improve memory and support brain health in both young and aged animals. The researchers found that rats given 1-MX for 12 days performed better on a memory task and showed increases in key brain chemicals linked to learning, neuroprotection, and antioxidant defenses.

Caffeine is one of the most widely consumed psychoactive substances in the world, known for its stimulating effects and ability to enhance attention and short-term memory. However, much of caffeine’s activity in the body results from how it is broken down into other compounds. One of the primary byproducts of caffeine metabolism is paraxanthine, which has been shown to boost memory and brain activity in both humans and animals. Another compound that forms as caffeine is further metabolized is 1-MX.

Despite the prevalence of 1-MX in the body after caffeine consumption, its potential effects on cognition and brain health had never been directly tested. The authors of the new study aimed to fill this gap by investigating whether daily supplementation of 1-MX could improve memory performance and affect various brain chemicals associated with learning, aging, and neurodegeneration.

To explore the effects of 1-MX, researchers used 32 male Swiss albino rats divided evenly by age: 16 young rats (8 weeks old) and 16 aged rats (16 months old). Each age group was further divided into a control group and a group that received 1-MX. The supplemented animals were given a human-equivalent daily dose of 100 milligrams of 1-MX, delivered orally for 12 consecutive days.

On the 15th day, the rats completed a widely used memory test known as the Morris water maze. In this task, animals are placed in a pool of water and must locate a hidden platform using spatial cues from the environment. The main measure of learning is escape latency, or how long it takes the animal to find the platform. A shorter escape time suggests better memory performance.

After the final testing day, the rats were euthanized, and their brains were examined for several biological markers. The researchers measured levels of neurotransmitters including acetylcholine, dopamine, and gamma-aminobutyric acid (GABA), as well as other brain chemicals associated with memory, antioxidant activity, and aging. These included brain-derived neurotrophic factor (BDNF), glutathione, catalase, cyclic GMP, and amyloid beta.

Rats that received 1-MX supplementation performed significantly better on the memory task. Young rats in the 1-MX group showed a 39% reduction in escape latency compared to controls, while aged rats improved by 27%. Although younger animals tended to learn the task more quickly overall, both age groups benefited from the supplement.

The biological analyses revealed that 1-MX had widespread effects on brain chemistry. Rats given 1-MX had higher levels of acetylcholine, dopamine, and GABA. These neurotransmitters play key roles in attention, motivation, inhibition, and learning. The increase in cyclic GMP, a molecule involved in signal transmission within cells, suggested improved synaptic communication.

The supplemented animals also showed signs of enhanced brain health. BDNF, a protein that supports the growth and survival of neurons, was elevated in the 1-MX group. Levels of glutathione and catalase—two important antioxidants—were also higher, especially in aged animals. This suggests that 1-MX may help defend against oxidative stress, a process that contributes to cognitive decline during aging.

Importantly, the study also found a reduction in amyloid beta 1–40, a protein fragment that can accumulate in the brain and is associated with the development of Alzheimer’s disease. The presence of lower amyloid beta levels suggests that 1-MX may have a protective effect against age-related neurological changes.

These findings suggest that 1-MX is more than just a metabolic byproduct of caffeine—it may play an active role in supporting cognitive function and brain health. The memory improvements observed in both young and old animals indicate that 1-MX could enhance learning regardless of age. The associated increases in neurotransmitters and neuroprotective compounds point to a possible mechanism for these cognitive benefits.

Although caffeine and its better-known metabolite paraxanthine have been studied extensively, this research is the first to directly examine 1-MX’s physiological effects. The fact that 1-MX improved memory and boosted brain markers similar to or beyond those seen with caffeine and paraxanthine suggests it may be a promising candidate for future cognitive enhancement research.

While the results are promising, several limitations should be noted. First, the study was conducted on rats, and the findings may not directly translate to humans. Animal brains differ in important ways from human brains, and the complex nature of human cognition requires additional investigation.

Second, the study used only one behavioral test to measure memory. Escape latency in the water maze provides insight into spatial learning, but it does not capture other aspects of cognitive function such as attention, problem-solving, or long-term memory. Future studies could include a broader range of cognitive tests to determine the full impact of 1-MX.

Third, only male rats were used in this experiment. There is growing recognition that sex differences can influence how drugs and supplements affect the brain, so future research should include female animals to better understand whether the observed benefits extend across sexes.

In addition, the researchers measured brain chemical levels from the entire brain, rather than isolating specific regions such as the hippocampus or prefrontal cortex, which are directly involved in memory and learning. Measuring neurotransmitter changes in specific brain regions could provide a more detailed understanding of how 1-MX affects cognitive processes.

Lastly, the duration of the study was relatively short. While 12 days of supplementation was enough to detect changes in memory and brain chemistry, it remains unclear whether these effects would persist over time or whether different doses would be more or less effective. Long-term studies and dose-response trials will be needed to explore the safety and sustained impact of 1-MX supplementation.

“In conclusion, the caffeine metabolite 1-MX is physiologically active and increases memory, neurotransmitter levels, neuroplasticity and several markers of neuronal health. Our study demonstrates that 1-MX is a new nootropic dietary ingredient supporting brain health and performance,” the researchers wrote.

The study, “1-Methylxanthine enhances memory and neurotransmitter levels,” was authored by Ralf Jäger, Sidney Abou Sawan, Marco Orrú, Grant M. Tinlsey, Martin Purpura, Shawn D. Wells, Kylin Liao, and Ashok Godavarthi.