tuneTypical Dose
10-20 mg per day
Natural Compound
PQQ
Pyrroloquinoline quinone (methoxatin)
Evidence TierCWADA NOT PROHIBITED
watchEffect Window
8-12 weeks for cognitive and energy effects.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
PQQ (pyrroloquinoline quinone) is a redox-active compound studied for mitochondrial signaling and oxidative stress modulation. It is used for fatigue, sleep quality, and mitochondrial function-related goals.
Small human studies suggest possible improvements in fatigue, sleep quality, and mitochondrial-related biomarkers, but clinical outcome evidence is still thin. A newer mild-cognitive-impairment trial found higher BDNF and some brain-metabolite shifts after 6 weeks, while cognitive improvements were only trend level. That keeps PQQ in the plausible-but-early category rather than the proven nootropic category.
Redox cofactor that activates PGC-1α and CREB, stimulating mitochondrial biogenesis and NGF production.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Stimulates mitochondrial biogenesis via PGC-1α activation
- Mild improvements in working memory and attention
Secondary Outcomes
- Improved sleep quality
- Fatigue reduction
- Nerve growth factor stimulation
Safety
Contraindications and Interactions
Contraindications
- Pregnancy (insufficient data)
- Lactation (insufficient data)
Side effects
- Headache
- Drowsiness at higher doses
Interactions
- None significant
Avoid if
- Pregnant or lactating (lack of safety data)
Evidence
Study-level References
pqq-SRC-001Open-label trial
Sourceopen_in_newNakano M, Yamamoto T, Okamura H, Tsuda A, Kowatari Y. Effects of Oral Supplementation with Pyrroloquinoline Quinone on Stress, Fatigue, and Sleep. Functional Foods in Health and Disease. 2012;2(8):307-324.
Population: Adult office workers with fatigue and disordered sleep complaints.
Dose protocol: PQQ disodium salt 20 mg/day for 8 weeks in workers with fatigue and sleep complaints
Key findings: Subjective sleep, fatigue, mood, and quality-of-life scores improved over 8 weeks, with sleep-quality changes tracking cortisol awakening response.
Notes: Useful as the direct sleep-fatigue signal, but confidence stays limited because the study was open label and uncontrolled.
Paper content
This 8-week open-label study enrolled 17 workers with fatigue and sleep complaints and gave 20 mg/day of PQQ disodium salt. Subjective mood, fatigue, sleep, and quality-of-life scores improved from baseline, and sleep-related score changes tracked cortisol awakening response. Because the trial had no placebo control and relied heavily on self-report endpoints, it provides only preliminary support for sleep-fatigue benefit claims.
pqq-SRC-002Randomized, placebo-controlled, double-blind parallel-group trial
Sourceopen_in_newItoh Y, Hine K, Miura H, Uetake T, Nakano M, Takemura N, Sakatani K. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions. Adv Exp Med Biol. 2016;876:319-325. doi:10.1007/978-1-4939-3023-4_40. PMID:26782228.
Population: Healthy older adults.
Dose protocol: BioPQQ 20 mg/day for 12 weeks versus placebo in healthy older adults
Key findings: Selective-attention outcomes favored PQQ, and the lower-baseline subgroup improved on Touch M working-memory-adjacent performance without safety signals.
Notes: Best direct cognition-supportive human trial in older adults, but the effect depends on subgroup and analytic details rather than a broad unambiguous win.
Paper content
This 12-week placebo-controlled trial tested 20 mg/day of PQQ disodium salt in 41 healthy older adults. The strongest signal was for selective attention and working-memory-adjacent performance rather than broad global cognition. Stroop interference worsened less than placebo after outlier handling, and participants with lower starting Touch M scores improved meaningfully, while routine safety monitoring remained unremarkable. The findings support a preliminary cognitive-aging signal, but the subgroup dependence and analytic fragility keep confidence modest.
pqq-SRC-003Randomized controlled trial
Sourceopen_in_newThe 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. doi:10.1016/j.jnha.2024.100287. PMID:38908296.
Population: Elderly individuals with mild cognitive impairment.
Dose protocol: Dihydrogen-PQQ mixture twice daily for 6 weeks in elderly adults with mild cognitive impairment
Key findings: Serum BDNF increased and several brain-metabolism markers shifted, while cognitive outcomes showed only non-significant trend-level improvement.
Notes: Useful modernization study because it narrows the cognition claim and ties PQQ more to exploratory biomarker work than to proven nootropic benefit.
Paper content
In older adults with mild cognitive impairment, a dihydrogen-PQQ mixture raised BDNF and shifted brain-metabolism markers over 6 weeks, but clear cognitive improvement was not established. This is a useful modernization study because it ties PQQ claims to exploratory biomarker effects rather than to proven nootropic benefit.
pqq-SRC-004Crossover human supplementation studies
Sourceopen_in_newHarris CB, Chowanadisai W, Mishchuk DO, Satre MA, Slupsky CM, Rucker RB. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013;24(12):2076-2084. doi:10.1016/j.jnutbio.2013.07.008. PMID:24231099.
Population: Healthy adult volunteers in two short human supplementation studies.
Dose protocol: Single 0.2 mg/kg PQQ dose and 0.3 mg/kg/day for 3 days in healthy adults
Key findings: CRP and IL-6 decreased and urinary metabolite patterns shifted in a direction interpreted as enhanced mitochondrial oxidative metabolism, while standard clinical chemistry stayed unchanged.
Notes: Stronger as a mechanistic and biomarker bridge than as proof of a durable clinical benefit.
Paper content
This short crossover human study found that oral PQQ changed inflammatory and mitochondrial-related biomarker patterns rather than standard clinical endpoints. A single 0.2 mg/kg dose was associated with lower malondialdehyde-related TBAR values over 48 hours, and 0.3 mg/kg/day for 3 days lowered CRP and IL-6 while shifting urinary metabolites in a direction interpreted as more oxidative mitochondrial metabolism. It is useful as biomarker support, but it does not establish durable clinical benefit.
pqq-SRC-005Narrative review
Sourceopen_in_newYan T, Nisar MF, Hu X, Chang J, Wang Y, Wu Y, Liu Z, Cai Y, Jia J, Xiao Y, Wan C. Pyrroloquinoline Quinone (PQQ): Its impact on human health and potential benefits: PQQ: Human health impacts and benefits. Curr Res Food Sci. 2024;9:100889. doi:10.1016/j.crfs.2024.100889. PMID:39513102.
Population: Review of preclinical and human PQQ literature across metabolic, neurologic, cardiovascular, and aging contexts.
Dose protocol: Narrative review of preclinical and human PQQ literature
Key findings: Review catalogs broad potential benefit areas but repeatedly highlights the need for stronger human dose-finding and long-term clinical trials.
Notes: Context source only. It is useful for literature coverage and caveats, not for upgrading confidence on its own.
Paper content
This 2024 review summarizes a wide range of proposed PQQ benefits across cognition, metabolism, cardiovascular health, inflammation, and anti-aging. It is useful as a map of the literature, but much of the enthusiasm is driven by preclinical or mechanistic work rather than robust human trials. Its value for the PQQ record is therefore contextual and bibliographic, not as stand-alone proof for broad clinical claims.