Pyrroloquinoline quinone (PQQ), by some called "the fourteenth vitamin", also known as methoxatin deserves a full blog post due to its health & beauty benefits. PQQ, discovered in 1979, is an aromatic tricyclic o-quinone, a small quinone molecule, naturally found in various foods (Kumazawa et al., 1995; Mitchell et al., 1999), and plays a crucial role in various biological processes, particularly in cellular energy production and antioxidant defence [1].
Chemical structure and properties PQQ is water-soluble and it´s molecular formula is C14H6N2O8 - see picture. It is structurally similar to other quinones, like for example Coenzyme Q10, however possesses unique redox (oxidation reduction) properties that contribute to its biological activities [1]. PQQ is highly stable and efficient in redox cycling, can undergo multiple redox cycles, allowing it to participate in numerous biochemical reactions with various compounds. It does not easily self-oxidize or condense into inactive forms [2]. When compared on a molar basis, PQQ can be 100 to 1000 times more efficient in redox cycling assays than other enediols, such as ascorbic acid (vitamin C) and menadione, as well as many isoflavonoids, phytoalexins and polyphenolic compounds [2]. The reduced form of PQQ (PQQH2) can act as an aroxyl radical scavenger, even more effectively than α-tocopherol against peroxyl radicals [2]. Peroxyl radicals (ROO•) are involved in lipid peroxidation and contribute oxidative stress in biological systems, potentially damaging DNA, proteins, and lipids. 
PQQ is thus an exceptionally potent antioxidant: [3]
▌Direct scavenging of reactive oxygen species (ROS) ▌Regeneration of other antioxidants like vitamin E ▌Induction of antioxidant enzymes such as superoxide dismutase and catalase [4] Mitochondrial function and biogenesis One of the most significant roles of PQQ is its impact on mitochondrial function and biogenesis. Mitochondria are the powerhouses of cells, responsible for producing the majority of cellular energy in the form of ATP (adenosine triphosphate) [5]. PQQ has been show to
Anti-inflammatory effects PQQ exhibits anti-inflammatory properties, which may contribute to its potential in managing chronic inflammatory conditions: Reduction of inflammatory markers: PQQ has been shown to decrease levels of pro-inflammatory cytokines such as TNF-α and IL-6 [10] Modulation of NF-κB signaling: PQQ can inhibit the activation of NF-κB, a key transcription factor involved in inflammatory responses [11] Neuroprotection PQQ has demonstrated significant neuroprotective effects in various studies, particularly in the areas of cognitive function, protection against neurotoxins, and nerve growth factor (NGF) production.
Metabolic health ▌Glucose metabolism: Some studies suggest that PQQ can enhance insulin sensitivity and glucose tolerance. ▌Lipid metabolism: PQQ has been shown to activate AMPK (AMP-activated protein kinase), a key regulator of energy metabolism and linked to cellular increases in the NAD+/NADH ratio and increased sirtuins expression [16]. Both NAD+ and sirtuins were key topics of David Sinclair´s longevity research. Sirtuins are a family of proteins known to be involved in epigenetic regulation through their deacetylase activity. Sleep quality & quantity Sleep quality and quantity are crucial for overall health and beauty, with experts generally recommending 7-9 hours of sleep daily for adults. Recent research has shown that Pyrroloquinoline quinone (PQQ) can significantly improve sleep quality, offering a promising avenue for those struggling with sleep issues. A clinical trial involving 17 adults who took 20 mg of PQQ daily for eight weeks demonstrated notable improvements in sleep onset, maintenance, and duration. These improvements were measured using two well-established sleep assessment tools: the Oguri-Shirakawa-Azumi Sleep Inventory and the Pittsburgh Sleep Quality Index [9][17]. The study also found a correlation between these improvements and changes in the cortisol awakening response, providing biomarker-supported evidence of enhanced sleep quality. The mechanisms behind PQQ's sleep-enhancing effects are multifaceted:
PQQ is naturally present in various foods, including: ▌Fermented soybeans (natto) ▌Green peppers ▌Kiwi ▌Parsley ▌Tea ▌Papaya ▌Spinach ▌Celery [1] ▌Dark chocolate PQQ can be present in human body, even in breast milk due to diet, because only bacteria can synthesise PQQ. SKIN HEALTH AND BEAUTY Clinical Studies on PQQ in Skincare A clinical study conducted by Dr. Zoe Diana Draelos and colleagues investigated the effects of a topical formulation containing a modified form of PQQ called topical allyl pyrroloquinoline quinone (TAP) on skin aging. on 40 subjects over a 12 week period. The study findings included: ▌Improved skin texture and dullness: Significant improvements were observed in skin texture and dullness after 4 weeks of twice-daily application (both p<0.0001) ▌Reduced appearance of lines and wrinkles: The study reported improvements in the appearance of fine lines and wrinkles (p=0.01) ▌Histological improvements: Histologic evaluation demonstrated reductions in solar elastosis from baseline at 6 weeks (33%, p=0.01) and 12 weeks (60%, p=0.002). ▌Improvements were also noted in skin tone at week 4 (p=0.01). ▌Significantly increased expression of DNA methyltransferase (DNMT3A, DNMT3B), cytochrome oxidase assembly factor-10 (COX10), and tumor protein-53 (TP53) genes (all p<0.05), indicating enhanced support of epidermal homeostasis, renewal, and repair. Increasing or decreasing DNA methyltransferase is considered an epigenetic modification:
▌Increased expression of heat shock protein 60 (HSPD1) and thioredoxin reductase (TXNRD1) occurred in tissues treated with TAP versus control (p<0.05), indicating enhanced antioxidative response and adaptation. Cell senescence PQQ protected human dermal fibroblasts (HDFs) from UVA-induced senescence [22]. This is supported by the study showing that PQQ treatment reduced the percentage of senescent cells stained by X-gal following UVA irradiation compared to the UVA-only group [22]. PQQ has demonstrated significant anti-senescence properties in various studies. In a study using Bmi-1 deficient mice, which exhibit accelerated aging, PQQ supplementation was found to reduce cell senescence markers in the skin [23]. The researchers observed that PQQ intake decreased levels of matrix metalloproteinases (MMPs), which are associated with cellular senescence and tissue degradation. PQQ supplementation was shown to rescue cellular senescence parameters in articular cartilage [24]. The researchers found that PQQ inhibited the development of the senescence-associated secretory phenotype (SASP), which is characterized by increased secretion of inflammatory cytokines and contributes to tissue degeneration. DNA damage In the skin aging study (mice), PQQ supplementation was found to significantly reduce oxidative stress and DNA damage [23]. This protective effect was attributed to PQQ's ability to maintain redox balance and inhibit the DNA damage response pathway. Furthermore, in the osteoarthritis study, PQQ treatment was observed to mitigate DNA damage in chondrocytes [24]. Skin barrier & collagen PQQ has been shown to have positive effects on the skin barrier (mice). The study revealed that PQQ supplementation improved skin thickness and collagen structure, which are important components of the skin's barrier function [23]. Recommended dosage for supplementation The optimal dosage of PQQ for supplementation can vary depending on the intended use and individual factors. However, based on available research and expert recommendations: 1. General health benefits: Typical doses range from 10 to 20 mg per day [1]. 2. Cognitive function: Studies have used doses of 20 mg per day for cognitive benefits. 3. Skin health: For skin benefits, doses of 10 to 20 mg per day have been suggested, although more research is needed to establish optimal dosages for dermatological applications. It is important to consult with a healthcare provider before starting any new supplement regimen, as dosage requirements may vary based on individual health status and needs. PQQ in skincare products PQQ is an interesting bioactive ingredient to be incorporated into skincare products due to its potential benefits for skin health, beauty and regeneration. When looking for PQQ in skincare products, it may be listed under various names, including: ▌Pyrroloquinoline quinone ▌Methoxatin ▌BioPQQ (a patented form of PQQ) The efficacy and safety in skincare products depends on the concentration of PQQ, overall formulation and other ingredients in the formula. Safety and tolerability PQQ has generally been found to be safe and well-tolerated in both animal and human studies. However, as with any supplement or new skincare ingredient, there are some considerations: 1. Oral supplementation: Studies using oral PQQ supplements at doses up to 20 mg per day have reported no significant adverse effects in short-term use. 2. Topical application: The Draelos study on topical PQQ application reported that the product was highly tolerable, with no significant adverse reactions. 3. Long-term safety: While short-term studies have shown good safety profiles, more research is needed to establish the long-term safety of PQQ supplementation and topical use. 4. Potential interactions: As with any supplement, PQQ may interact with certain medications or other supplements. Individuals taking medications or with pre-existing health conditions should consult a healthcare provider before using PQQ supplements. 5. Pregnancy and breastfeeding: Due to limited research, pregnant and breastfeeding women are generally advised to avoid PQQ supplementation unless directed by a healthcare provider [1]. PQQ could be a game-changer for (skin) health and beauty. While the science looks promising, we're still in the early stages of understanding all that PQQ can do. As with any supplement or skincare ingredient, always consult a qualified healthcare professional to determine what the most suitable approach is for your health and beauty goals. Take care Anne-Marie References: [1] Harris, C. B., et al. (2013). Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem, 24(12), 2076-2084. [2] Akagawa M, et al. Recent progress in studies on the health benefits of pyrroloquinoline quinone. Bioscience, Biotechnology, and Biochemistry. 2016;80(1):13-22 [3] Misra, H. S., et al. (2012). Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria. FEBS Lett, 586(22), 3825-3830. [4] Qiu, X. L., et al. (2009). Protective effects of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Neurosci Lett, 464(3), 165-169. [5] Chowanadisai, W., et al. (2010). Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem, 285(1), 142-152. [6] Stites, T., et al. (2006). Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr, 136(2), 390-396. [7] Bauerly, K., et al. (2011). Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS One, 6(7), e21779. [8] Zhang, Y., et al. (2009). Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons. Neurosci Lett, 455(3), 174-179. [9] Nakano, M., et al. Effects of oral supplementation with pyrroloquinoline quinone on stress, fatigue, and sleep. Funct Foods Health 2012 [10] Liu, Y., Jiang, Y., Zhang, M., Tang, Z., He, M., Bu, P., & Li, J. (2020). Pyrroloquinoline quinone ameliorates skeletal muscle atrophy, mitophagy and fiber type transition induced by denervation via inhibition of the inflammatory signaling pathways. Annals of Translational Medicine, 8(5), 207. [11] Wen, J., Shen, J., Zhou, Y., Zhao, X., Dai, Z., & Jin, Y. (2020). Pyrroloquinoline quinone attenuates isoproterenol hydrochloride-induced cardiac hypertrophy in AC16 cells by inhibiting the NF-κB signaling pathway. International Journal of Molecular Medicine, 45(3), 873-885. [12] Tamakoshi, M., Suzuki, T., Nishihara, E., Nakamura, S., & Ikemoto, K. (2023). Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults. Food & Function, 14(6), 3201-3211. [13] Zhang, Q., Zhang, J., Jiang, C., Qin, J., Ke, K., & Ding, F. (2014). Involvement of ERK1/2 pathway in neuroprotective effects of pyrroloquinoline quinine against rotenone-induced SH-SY5Y cell injury. Neuroscience, 270, 183-191. [14] Zhang, Q., Shen, M., Ding, M., Shen, D., & Ding, F. (2011). The neuroprotective effect of pyrroloquinoline quinone on traumatic brain injury. Journal of Neurotrauma, 28(3), 359-366. [15] Yamaguchi, K., Sasano, A., Urakami, T., Tsuji, T., & Kondo, K. (1993). Stimulation of nerve growth factor production by pyrroloquinoline quinone and its derivatives in vitro and in vivo. Bioscience, Biotechnology, and Biochemistry, 57(7), 1231-1233. [16] Mohamad Ishak NS, Ikemoto K. Pyrroloquinoline-quinone to reduce fat accumulation and ameliorate obesity progression. Front Mol Biosci. 2023 [17] Mitsugu Akagawa et al. Bioscience, Biotechnology, and Biochemistry Recent progress in studies on the health benefits of pyrroloquinoline quinone 2015 [18] Kazuto Ikemoto et al. The effects of pyrroloquinoline quinone disodium salt on brain function and physiological processes The Journal of Medical Investigation 2024 [19] Kowalczyk P, Sulejczak D, Kleczkowska P, Bukowska-Ośko I, Kucia M, Popiel M, Wietrak E, Kramkowski K, Wrzosek K, Kaczyńska K. Mitochondrial Oxidative Stress-A Causative Factor and Therapeutic Target in Many Diseases. Int J Mol Sci. 2021 [20] Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 2013 [21] 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 [22] Zhang C, Wen C, Lin J, Shen G. Protective effect of pyrroloquinoline quinine on ultraviolet A irradiation-induced human dermal fibroblast senescence in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway. Mol Med Rep. 2015 [23] Li J, Liu M, Liang S, Yu Y, Gu M. Repression of the Antioxidant Pyrroloquinoline Quinone in Skin Aging Induced by Bmi-1 Deficiency. Biomed Res Int. 2022 [24] Qin R, Sun J, Wu J, Chen L. Pyrroloquinoline quinone prevents knee osteoarthritis by inhibiting oxidative stress and chondrocyte senescence. American Journal of Translational Research. 2019 [25] Lee, J.-J.; Ng, S.-C.; Hsu, J.-Y.; Liu, H.; Chen, C.-J.; Huang, C.-Y.; Kuo, W.-W. Galangin Reverses H2O2-Induced Dermal Fibroblast Senescence via SIRT1-PGC-1α/Nrf2 Signaling. Int. J. Mol. Sci. 2022, 23, 1387.
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