PQQ (Pyrroloquinoline quinone)

1. Introduction

Pyrroloquinoline quinone (PQQ), chemically known as 4,5-dihydro-4,5-dioxo-1H-pyrrolo [2,3-f]quinoline-2,7,9-tricarboxylic acid, is a small, water-soluble quinone molecule. It is often referred to as a vitamin-like accessory factor or a novel micronutrient, as its absence in the diet of mammals has been shown to produce deficiency-like symptoms that are reversed upon repletion [1]. PQQ is not currently classified as a vitamin for humans, but its fundamental biological roles are widely recognized.

Mechanism of Action

PQQ’s primary mechanism of action involves its potent ability to participate in redox cycling and its function as an enzyme cofactor.

1. Antioxidant Activity: PQQ and its reduced form (PQQH₂) are highly effective in carrying out continuous redox reactions. PQQH₂ is an extremely powerful antioxidant, estimated to be 100 to 1000 times more efficient in redox cycling than other common antioxidants like Vitamin C (ascorbic acid) [1]. This allows it to protect cells from oxidative damage by neutralizing free radicals.
2. Mitochondrial Biogenesis: PQQ is a key signaling molecule that influences the expression of genes involved in mitochondrial function and growth. It promotes mitochondriogenesis (the creation of new mitochondria) by enhancing NAD+-dependent sirtuin activity, which in turn upregulates key transcription factors such as PGC-1$alpha$, NRF-1, NRF-2, and TFAM [1]. This role in boosting mitochondrial health is central to PQQ’s potential benefits for energy metabolism and anti-aging.
3. Enzyme Cofactor: PQQ serves as a catalytic accessory factor for mammalian dehydrogenases, such as lactate dehydrogenase, optimizing the oxidation of NADH to NAD+ [1].

2. Chemical Composition/Key Bioactive Roles

The following table summarizes the key bioactive roles of PQQ in human physiology:

Key Bioactive Role	Mechanism of Action
Mitochondrial Biogenesis	Promotes the growth of new mitochondria by upregulating key signaling proteins (PGC-1$alpha$, NRF-1/2) and enhancing sirtuin activity.
Potent Antioxidant	PQQH₂ participates in redox cycling, neutralizing free radicals up to 1,000 times more effectively than Vitamin C on a molar basis.
Enzyme Cofactor	Acts as an accessory factor for mammalian dehydrogenases, optimizing cellular energy metabolism.
Neuroprotection	Protects neurons from oxidative stress and neurotoxicity, particularly in models of neurodegenerative diseases [3].

3. Health Benefits

PQQ supplementation has been studied for its potential benefits across several areas of human health, primarily driven by its effects on mitochondrial function and oxidative stress.

Cognitive Function and Neuroprotection

PQQ has demonstrated significant neuroprotective properties in various experimental models [3]. In human studies, PQQ has been shown to improve cognitive functions. A randomized, double-blind, placebo-controlled study found that PQQ disodium salt improved cognitive functions, specifically cognitive flexibility and executive speed, in young adults (aged 20–40 years) over an 8-week period [4]. Another clinical study indicated that PQQ supplementation could lead to improvements in memory, attention, and overall cognitive performance [5].

Cardiovascular Health

The strong antioxidant and mitochondrial-supportive properties of PQQ suggest a role in maintaining heart health. PQQ has been shown to protect cardiomyocytes (heart muscle cells) from oxidative damage and to improve overall cardiac function in animal models [2]. Clinical studies have also indicated potential benefits for cardiovascular health, including improvements in lipid metabolism and reduced inflammation, which are key risk factors for heart disease [5].

Energy Metabolism and Weight Management

By promoting mitochondrial biogenesis, PQQ can support efficient energy production and metabolic function. Research suggests that PQQ may play a role in lipid metabolism regulation and is linked to potential benefits for weight control and reducing the accumulation of visceral and hepatic fat [5, 6].

4. Dosage and Usage

Recommended Dosages

The typical and generally recognized safe dosage for PQQ supplementation ranges from 10 mg to 40 mg per day.

• Common Dose: Most supplements contain PQQ in the range of 10 mg to 20 mg per day [7].
• Clinical Trials: Clinical studies have safely used PQQ disodium salt at doses up to 100 mg per day for up to 24 weeks without raising safety concerns [8].
• Safety Margin: Based on animal toxicology data and a safety margin of 100, the safe upper limit in adult humans is estimated to be around 240 mg per person per day [1].

Food Sources

PQQ is found naturally in various foods, though the concentrations are typically low (in the nanogram per gram/milliliter range). Dietary sources include:

• Fermented foods (e.g., natto)
• Vegetables (e.g., spinach, parsley, celery, green peppers)
• Fruits (e.g., kiwi, papaya)
• Beverages (e.g., green tea, wine, cocoa)
• Legumes [7, 9]

5. Safety and Precautions

Safety and Side Effects

PQQ is generally considered safe for most healthy adults when taken at recommended dosages (up to 100 mg/day). Toxicology studies have established a high safety profile, with no reported toxicity or genotoxicity [8]. Minimal side effects, such as mild headache or insomnia, have been anecdotally reported but are rare and not consistently linked to PQQ in clinical trials [7].

Contraindications and Warnings

• High Doses: While the safe upper limit is high, excessive doses (significantly above 100 mg/day) may pose a theoretical risk of kidney damage, as indicated by some animal toxicology studies [7]. Users should adhere to the recommended daily dosage.
• Pregnancy and Nursing: Due to a lack of sufficient data, PQQ supplementation is not recommended for women who are pregnant or nursing.
• Children: PQQ is not recommended for children as safety and efficacy data are limited.

Drug Interactions

No significant or serious drug interactions have been definitively established. However, PQQ’s role in mitochondrial function and energy metabolism suggests caution when combined with medications that affect these pathways. Consultation with a healthcare provider is advised for individuals taking:

• Diabetes Medications: PQQ may influence metabolic markers.
• Blood Pressure Medications: Due to PQQ’s potential benefits for cardiovascular health.

6. References

1. Jonscher KR, Chowanadisai W, Rucker RB. Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention. Biomolecules. 2021 Sep 30;11(10):1441. https://pmc.ncbi.nlm.nih.gov/articles/PMC8533503/
2. Pyrroloquinoline quinone (PQQ) improves pulmonary hypertension by regulating mitochondrial and metabolic functions. Sciencedirect. 2022. https://www.sciencedirect.com/science/article/abs/pii/S1094553922000475
3. Pyrroloquinoline quinone: a potential neuroprotective agent for Parkinson’s disease. Neural Regen Res. 2025 Jan. https://journals.lww.com/nrronline/fulltext/2025/01000/pyrroloquinoline_quinone__a_potential.5.aspx
4. Tamakoshi M, et al. Pyrroloquinoline quinone disodium salt improves brain functions in young adults: A randomized, double-blind, placebo-controlled study. Food Funct. 2023. https://pubs.rsc.org/en/content/articlehtml/2023/fo/d2fo01515c
5. Yan T, et al. Pyrroloquinoline Quinone (PQQ): Its impact on human health and potential benefits. Heliyon. 2024. https://www.sciencedirect.com/science/article/pii/S2665927124002156
6. Mohamad Ishak NS, et al. Pyrroloquinoline-quinone to reduce fat accumulation and obesity-related metabolic dysfunction: A review of preclinical studies. Front Mol Biosci. 2023. https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1200025/full
7. PQQ Supplements: Overview, Benefits, and Side Effects. Healthline. 2020. https://www.healthline.com/nutrition/pqq-supplement
8. Safety of pyrroloquinoline quinone disodium salt as a novel food ingredient for use in food supplements. EFSA Journal. 2017. https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.5058
9. A behind-the-scenes look at the longevity vitamin PQQ. Berkeley Chemistry News. 2020. https://chemistry.berkeley.edu/news/behind-scenes-look-longevity-vitamin-pqq