How PQQ Works in the Brain

Pyrroloquinoline quinone (PQQ) is a small antioxidant molecule that supports mitochondrial function and cellular energy metabolism. It occurs naturally in certain foods, including natto, parsley, green tea, kiwi, peppers, spinach, and breast milk, and is also produced by some bacteria during fermentation.

Based on published research, PQQ appears to support brain health through several mechanisms:

• Mitochondrial biogenesis. PQQ supports the formation of new mitochondria, which are essential for cellular energy production.
• Antioxidant protection. PQQ helps protect neurons from oxidative stress.
• Energy metabolism. It modulates signaling pathways involved in cellular energy production.
• Neuroplasticity. Research suggests PQQ may influence pathways linked to synaptic adaptation and resilience.
• Inflammation regulation. PQQ has been studied for its anti-inflammatory properties.

There is moderate evidence of benefit from human clinical trials, though the evidence base remains smaller and more preliminary than for some other cognitive-support ingredients.

Clinical Evidence in Older Adults

Baltic et al. (2024) — 6-Week Pilot RCT

In a 6-week randomized controlled trial, 34 elderly participants with mild cognitive impairment were assigned to PQQ or placebo. The PQQ arm showed improvement in the primary endpoint, brain-derived neurotrophic factor (BDNF), although baseline BDNF levels differed substantially between groups, which limits interpretation. Some additional improvements were reported. Overall, this was not a strong efficacy study, but it did provide useful safety information.

Baltic S, Nedeljkovic D, et al. The Impact of Six-Week Dihydrogen-Pyrroloquinoline Quinone Supplementation on Mitochondrial Biomarkers, Brain Metabolism, and Cognition in Elderly Individuals With Mild Cognitive Impairment: A Randomized Controlled Trial. J Nutr Health Aging. 2024;28(8):100287. doi:10.1016/j.jnha.2024.100287.

Tamakoshi et al. (2023) — 12-Week RCT

Tamakoshi et al. enrolled 62 adults aged 20 to 65 and performed age-stratified analyses. Older adults aged 41 to 65 who received PQQ 20 mg daily for 12 weeks showed significant improvements in composite and verbal memory compared with placebo. The study used validated cognitive test batteries and found that benefits in older adults were specific to memory domains, with effects emerging after 12 weeks of supplementation. Younger adults aged 20 to 40 showed improvements in cognitive flexibility, processing speed, and execution speed after 8 weeks.

Tamakoshi M, Suzuki T, Nishihara E, Nakamura S, Ikemoto K. Pyrroloquinoline Quinone Disodium Salt Improves Brain Function in Both Younger and Older Adults. Food & Function. 2023;14(5):2496–2501. doi:10.1039/d2fo01515c.

Itoh et al. (2016) — 12-Week RCT

Itoh et al. studied 41 healthy elderly participants who received 20 mg PQQ daily for 12 weeks. The PQQ group demonstrated improvements in selective attention, measured by the Stroop test, and visuospatial cognitive function, measured by the Touch M test, particularly among those with lower baseline scores. The study also reported increased cerebral blood flow in the prefrontal cortex, suggesting a possible physiological basis for the cognitive findings.

Itoh Y, Hine K, Miura H, et al. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions. Advances in Experimental Medicine and Biology. 2016;876:319–325. doi:10.1007/978-1-4939-3023-4_40.

Nakano et al. (2016) — Non-Controlled Study

Nakano et al. investigated the effects of PQQ on cerebral blood flow and oxygen metabolism in 20 healthy adults aged 50 to 70. This was not a placebo-controlled study. After 12 weeks of supplementation, increased hemoglobin concentration and oxygen metabolism in the prefrontal cortex were observed, correlating with Stroop test performance. Because the study did not directly measure robust clinical cognitive outcomes and lacked a control group, its findings should be considered suggestive rather than definitive.

Nakano M, Murayama Y, Hu L, et al. Effects of Antioxidant Supplements (BioPQQ™) on Cerebral Blood Flow and Oxygen Metabolism in the Prefrontal Cortex. Advances in Experimental Medicine and Biology. 2016;923:215–222. doi:10.1007/978-3-319-38810-6_29.

Summary

The PQQ clinical literature is promising but still limited. Randomized trials in older adults suggest potential benefits for memory, attention, and measures related to prefrontal cortex function, with a favorable safety profile at studied doses. Larger and longer trials would be helpful to strengthen confidence in the cognitive findings.