Pyrroloquinoline quinone (PQQ), chemically speaking, is an aromatic o-quinone compound with a molecular weight of 330.206 and the chemical formula C₁₄H₆N₂O₈. This unique molecular structure endows PQQ with many special properties. Among these, the o-quinone group plays a crucial role in the function of PQQ; it is the core site for PQQ to exhibit antioxidant properties and regulate mitochondrial function. As a coenzyme, PQQ differs significantly from traditional vitamins. It is not primarily a cofactor involved in enzyme catalysis like vitamins, but rather plays a key role in multiple physiological processes such as cell metabolism and signal transduction due to its diverse biological activities. This diverse activity is not only reflected in antioxidant effects but also extends to promoting mitochondrial biosynthesis, neuroprotection, and immune regulation, demonstrating its indispensable role in maintaining the health of organisms.
In nature, PQQ is widely distributed in various foods. Natto, a traditional fermented soybean product, contains a relatively rich amount of PQQ, approximately 61 ng per gram. Kiwifruit, a fruit rich in various vitamins and minerals, is also a good source of PQQ, with approximately 27 ng of PQQ per gram. Additionally, while green tea contains relatively small amounts of PQQ, its popularity as a tea-drinking habit makes it another potential source. The PQQ content in human milk is relatively stable, with a total content of 140-180 ng of PQQ and its derivative IPQ per milliliter. This level likely plays a crucial role in the growth and development of newborns, suggesting PQQ’s key nutritional role in early life. Overall, the average PQQ content in plant and animal-based foods ranges from 3.65 to 61.0 ng/g. Although the content is not high, it is important for maintaining normal physiological functions.
The biological sources of PQQ mainly include microbial fermentation and food conversion. In the microbial realm, microorganisms such as *Agrobacterium* can synthesize PQQ through their own metabolic pathways. These microorganisms are widespread in natural environments such as soil. Their metabolic activities not only affect the ecological balance of soil but also contribute to the formation of PQQ in nature. In terms of food conversion, some foods, during growth, processing, or fermentation, undergo biochemical reactions that transform substances into PQQ. For example, during the fermentation of natto, the action of microorganisms causes changes in the components of the raw materials, thereby producing PQQ. Unfortunately, the human body lacks the ability to synthesize PQQ, meaning that the body must rely on obtaining PQQ from external food sources to meet the physiological needs for PQQ. This dependence on exogenous intake highlights the importance of PQQ in food nutrition.
PQQ’s Core Health Benefits: Multi-System Protection Mechanism
(I) Antioxidant and Cell Protection Functions
In the microscopic world of cells, oxidative stress is like a potential storm, constantly threatening cellular health. PQQ, as a powerful guardian, provides a protective umbrella for cells in this storm with its outstanding antioxidant capacity. It is a super-strong free radical scavenger with extremely high affinity for reactive oxygen species such as hydroxyl radicals (HO・) and superoxide anions (O₂・–), rapidly binding to and eliminating them. Research data shows that PQQ’s scavenging efficiency for these free radicals is significantly higher than that of vitamin C; under the same conditions, PQQ’s rate of scavenging hydroxyl radicals is several times that of vitamin C. This highly efficient free radical scavenging ability allows PQQ to effectively inhibit lipid peroxidation. Lipid peroxidation is a key step in the oxidative stress process, leading to the oxidation of lipids in cell membranes, thereby damaging the structure and function of cell membranes. By inhibiting this reaction, PQQ directly protects the integrity of biological membrane structures such as mitochondrial membranes.
In animal experiments, the antioxidant protective effects of PQQ were fully validated. In a myocardial ischemia-reperfusion injury model, the experimental group treated with PQQ showed significantly reduced myocardial tissue damage, with the damaged area decreasing by approximately 40% compared to the control group. This is because a large number of free radicals are generated during myocardial ischemia-reperfusion, and PQQ can promptly scavenge these free radicals, reducing their damage to cardiomyocytes and thus protecting the normal function of myocardial tissue. PQQ also performed well in a liver oxidative stress model. After PQQ supplementation, the level of malondialdehyde (MDA), a marker of oxidative stress, in liver tissue decreased by 35%. MDA is a product of lipid peroxidation, and its reduction directly reflects the inhibitory effect of PQQ on oxidative stress in liver tissue, indicating that PQQ can effectively protect liver cells from oxidative damage and maintain normal liver metabolism and detoxification functions. These experimental results fully demonstrate the important role of PQQ in multi-organ antioxidant protection, providing strong experimental evidence for its application in the prevention and treatment of oxidative stress-related diseases.
(II) Neurological and Cognitive Optimization Effects
The brain, as the “command center” of the human body, plays a crucial role in maintaining normal function for life activities. PQQ, with its unique biological characteristics, plays an indispensable role in neuroprotection and cognitive function optimization. PQQ has the ability to cross the blood-brain barrier, allowing it to directly enter the brain and make “close contact” with neurons. Once in the brain, PQQ stimulates the secretion of nerve growth factor (NGF). Studies have found that PQQ can increase NGF secretion by 25%. NGF is a protein essential for neuronal growth, development, and survival. It promotes neuronal differentiation and survival, strengthens connections between neurons, and thus improves neuronal function. In a β-amyloid-induced neuronal damage model, the protective effect of PQQ is particularly significant. Abnormal aggregation of β-amyloid protein is one of the important pathological features of neurodegenerative diseases such as Alzheimer’s disease, leading to neuronal damage and death. PQQ can effectively improve this damage by regulating intracellular signaling pathways, reducing the toxic effects of β-amyloid protein on neurons, and promoting neuronal repair and regeneration.
In animal experiments, PQQ supplementation in rats with an Alzheimer’s disease model improved their accuracy in the maze test by 30%. The maze test is a commonly used method for assessing animal cognitive abilities; the improved accuracy indicates that PQQ can significantly improve the spatial learning and memory abilities of rats, which is closely related to PQQ’s role in promoting nerve growth factor secretion and protecting neurons. Human clinical studies have also confirmed the positive effects of PQQ on cognitive function. Studies on individuals with mild cognitive impairment showed that after 6 weeks of continuous supplementation with 20 mg/day of PQQ, the subjects’ brain oxygen saturation increased from 48.4% to 52.8%. Increased brain oxygen saturation means the brain receives a more sufficient oxygen supply, helping to maintain normal brain metabolism and function. Subjects also showed significant improvement in ADAS-Cog orientation scores (P=0.03), further demonstrating that PQQ can effectively improve cognitive function in individuals with mild cognitive impairment and is of great significance for preventing and delaying the progression of neurodegenerative diseases.
(III) Metabolic and Immune Regulatory Effects
In the field of metabolism, PQQ acts like a sophisticated “metabolic engineer,” playing a crucial role in maintaining the body’s energy balance and metabolic homeostasis. PQQ participates in key aspects of lipid metabolism by enhancing mitochondrial β-oxidation function. β-oxidation is the main pathway for fatty acid catabolism, and PQQ can increase the activity of β-oxidation-related enzymes, promoting fatty acid breakdown and thus reducing visceral fat accumulation. In a high-fat diet mouse model, PQQ supplementation reduced the volume of visceral fat cells by 22%, a result that clearly demonstrates the significant effect of PQQ in regulating lipid metabolism and reducing fat accumulation. Excessive visceral fat accumulation is closely related to various metabolic diseases such as insulin resistance and type 2 diabetes; this effect of PQQ provides a new approach for the prevention and improvement of these metabolic diseases.
In terms of immune regulation, PQQ also performs excellently, acting as an important regulator of the body’s immune system. PQQ can increase the CD4+/CD8+ cell ratio in the spleen. CD4+ and CD8+ cells are important cell subsets in the immune system, playing a crucial role in the immune response. Maintaining a balanced CD4+/CD8+ cell ratio is essential for maintaining normal immune function. PQQ also promotes the secretion of interleukin-2 (IL-2), an important cytokine that can activate immune cells such as T lymphocytes and enhance the body’s immune response. In a parenteral nutrition model, the immunomodulatory effect of PQQ was fully demonstrated, restoring up to 60% of the integrity of intestinal lymphoid organs. Parenteral nutrition often leads to a decline in intestinal immune function, while PQQ, by regulating immune cells and cytokines, effectively improves the intestinal immune microenvironment and promotes the repair and functional recovery of intestinal lymphoid organs. In summary, PQQ reduces the damage of oxidative stress to metabolism and immune cells through its antioxidant effects, provides sufficient energy and nutritional support to the immune system by regulating metabolic processes, and enhances immune function by directly regulating the activity of immune cells and cytokines. Thus, it constructs a triangular protection system of antioxidant, anti-inflammatory, and immune regulation to comprehensively maintain the body’s health.
Mitochondrial Biosynthesis: The Core Target of PQQ
Mitochondrial Biosynthesis: The Core Target of PQQ(I) Regulatory Mechanisms of Mitochondrial Biosynthesis
Mitochondria, as the cell’s “energy factory,” undergo a series of precise regulations in their biosynthesis. PQQ plays a crucial role in this process, primarily promoting mitochondrial biosynthesis by activating the PGC-1α/NRF-1 signaling pathway. PGC-1α is a key transcriptional coactivator. When PQQ binds to specific receptors on the cell surface, it triggers an intracellular signaling cascade, thereby activating PGC-1α. Activated PGC-1α interacts with other transcription factors, including NRF-1. NRF-1 is a nuclear respiratory factor that, in synergy with PGC-1α, specifically binds to the promoter region of mitochondrial DNA, promoting mitochondrial DNA transcription and replication, resulting in a significant increase in mitochondrial DNA copy number. Research data shows that PQQ supplementation can increase mitochondrial DNA copy number by 40%, a figure that vividly demonstrates the powerful promoting effect of PQQ on mitochondrial DNA synthesis.
The increase in mitochondrial DNA copy number directly leads to an increase in the number of mitochondria, especially in cells with high energy demands such as skeletal muscle cells. Simultaneously, PQQ can enhance ATP production efficiency, increasing it by 25%. As the cell’s direct energy currency, increased ATP production efficiency means the cell can obtain a more sufficient energy supply, thus meeting the energy needs of various physiological activities. Unlike coenzyme Q10, which mainly participates in the electron transport chain, PQQ regulates mitochondrial biosynthesis from its source. This unique mechanism gives PQQ an irreplaceable advantage in improving cellular energy metabolism, providing a solid energy foundation for maintaining normal cellular function and physiological activities.
(II) Key Value in Aging and Disease
With increasing age, the decline of mitochondrial function becomes an inevitable physiological phenomenon. This decline is mainly manifested in a decrease in the number of mitochondria, a decrease in mitochondrial membrane potential, and a decline in the activity of mitochondrial respiratory chain complexes. These changes ultimately lead to insufficient cellular energy supply, triggering a series of aging-related physiological changes. PQQ has shown great potential in reversing this aging process. In studies using aging mouse models, scientists found that PQQ supplementation restored 85% of the activity of mitochondrial complex IV in mice to youthful levels. Mitochondrial complex IV is a key enzyme in the mitochondrial respiratory chain; its restoration signifies improved mitochondrial respiratory function, allowing cells to metabolize energy more efficiently and thus alleviating age-related energy deficiency.
Mitochondrial dysfunction is also a common problem in patients with metabolic syndrome, leading to increased insulin resistance and consequently increasing the risk of metabolic diseases such as diabetes. PQQ offers an effective solution to this problem by improving skeletal muscle mitochondrial function. Studies have shown that PQQ can increase insulin sensitivity by up to 18%, primarily through enhancing mitochondrial energy metabolism and improving cellular glucose uptake and utilization. Increased insulin sensitivity helps maintain stable blood glucose levels, providing a new target for intervention in prediabetic patients. Improving mitochondrial function through PQQ supplementation holds promise as a new strategy for the prevention and treatment of metabolic syndrome and related diseases, bringing new hope to many patients with metabolic syndrome.
Scientific Applications of PQQ Supplements: From Dosage to Selection Strategies
(I) Suitable Population and Dosage Schedule
For most people who wish to maintain their health through PQQ supplementation, the recommended daily baseline dose is 10-20 mg. This dosage range is based on extensive basic research and preliminary human clinical trials. At this dose, PQQ can exert its antioxidant and mitochondrial biosynthesis-promoting physiological functions in the body, with a relatively high safety profile. For individuals with mild cognitive impairment, it is recommended to increase the dose to 20-30 mg to more effectively improve cognitive function. This is because individuals with mild cognitive impairment have already experienced some degree of neuronal damage and functional decline, requiring a higher dose of PQQ to stimulate the secretion of nerve growth factor, protect neurons, and thus improve cognitive ability.
Regarding the timing of administration, it is recommended to take it after breakfast and dinner. This is because food intake promotes gastrointestinal motility and the secretion of digestive juices, which helps dissolve and absorb PQQ, thereby improving its bioavailability. Clinical studies have provided strong evidence for the dosage-effect relationship of PQQ. In a study of healthy middle-aged and elderly individuals, subjects supplemented with 21.5 mg/day of PQQ for 12 consecutive weeks. The results showed significant improvements in their memory and attention (P<0.05), with no significant adverse reactions throughout the trial. This indicates that within a reasonable dosage range, PQQ can effectively improve cognitive function in middle-aged and elderly individuals with a proven safety profile. However, while there are currently no reports of clear serious adverse reactions from long-term intake of PQQ exceeding 50 mg/day, the potential risk of accumulation needs to be considered. Excessively high doses of PQQ may accumulate in the body, interfering with the metabolism of other nutrients and potentially causing adverse effects. Therefore, when supplementing with PQQ, the dosage should be strictly controlled to avoid the unknown risks associated with blindly pursuing high doses.
(II) Product Selection and Contraindications
When purchasing PQQ supplements, the purity and safety of the product are the primary considerations. Choose PQQ preparations with a purity of ≥95%. High purity ensures product efficacy and reduces the potential harm of impurities to the body. Products with FDA GRAS certification have their safety and quality recognized by authoritative institutions, giving consumers greater peace of mind. Besides purity and certification, the product’s formulation design is also crucial. Prioritize products containing coenzyme Q10, a substance vital for mitochondrial function. Coenzyme Q10 primarily participates in electron transport in the mitochondrial respiratory chain, working synergistically with PQQ to comprehensively enhance mitochondrial function and boost cellular energy metabolism. Products containing phospholipid carriers are also a good choice. Phospholipid carriers can bind with PQQ to form phospholipid complexes, increasing PQQ’s solubility in the intestines, promoting transmembrane transport, thereby enhancing intestinal absorption and improving PQQ’s bioavailability.
While PQQ is safe and beneficial for most people, it is not suitable for everyone. Pregnant women should strictly avoid PQQ supplementation. Animal studies have shown that high doses of PQQ can affect reproductive function and may lead to fetal developmental abnormalities. Individuals taking immunosuppressants should also avoid PQQ supplementation. PQQ has immunomodulatory effects and may interact with immunosuppressants, affecting their efficacy and potentially causing adverse reactions. To avoid interactions between PQQ and medications, it is recommended to take PQQ supplements at least 2 hours apart from other medications. This reduces the likelihood of simultaneous absorption in the gastrointestinal tract, lowers the risk of interaction, ensures both medications and PQQ function effectively, and protects the user’s health and safety.
(III) Withdrawal Effects and Long-Term Management
Understanding the potential effects of discontinuing PQQ supplementation and how to manage it long-term is crucial. In short-term withdrawal (<2 weeks), PQQ concentrations will rapidly drop to baseline levels within 48 hours. This is because PQQ is metabolized quickly in the body, and its levels decrease rapidly once supplementation stops. However, mitochondrial function indicators do not show significant fluctuations during short-term withdrawal. This is because after long-term stimulation by PQQ, mitochondrial function is improved and stabilized to a certain extent, and can maintain relatively normal function even without continuous PQQ stimulation in the short term.
For long-term users (>6 months), some adverse reactions may occur after discontinuing PQQ. Approximately 15% of long-term users experience temporary fatigue within 1-2 weeks after discontinuation. This is because long-term PQQ supplementation allows the body’s metabolic and energy production systems to adapt to its presence. Once discontinued, the body’s energy supply and metabolic functions cannot quickly adjust in the short term, leading to fatigue. To avoid this metabolic adaptation period, it is recommended to gradually reduce the dosage of PQQ, decreasing it by 5mg each week, while simultaneously consuming a diet rich in PQQ, such as increasing the intake of natto and spinach. This allows the body a gradual adaptation process, smoothly transitioning through the PQQ discontinuation phase, reducing adverse reactions, and ensuring the body’s health and stability.
As a cutting-edge nutrient bridging basic research and clinical applications, PQQ’s value far exceeds its role as a single antioxidant. By reshaping mitochondrial function, it opens up a new dimension of cellular-level anti-aging. Scientific supplementation requires consideration of individual health status, maximizing its multi-system protective effects under the premise of precise dosage and quality assurance, providing innovative solutions for proactive health management.
