Pyrroloquinoline Quinone (PQQ) is a potent antioxidant believed to optimize brain cells’ “power plant” mitochondria.
Pyrroloquinoline quinone (PQQ) is a novel nutrient considered to be important for biological functions related to immune, reproductive, cardiac and neurological health. Within the brain, PQQ:
- May boost energy via neurons’ mitochondria. This is probably PQQ’s biggest claim to fame as a potential nootropic.
- Promotes production of nerve growth factor (NGF). NGF helps with brain cell repair, maintenance, regeneration and communication.
- Acts as a neuron-protective antioxidant. Suggested to have 5,000X the antioxidant potency as Vitamin C,1 PQQ may help neutralize brain oxidative stress.
- Fights beta-amyloid plaques, the irregular protein clusters which are considered a major contributing factor to Alzheimer’s and dementia.
PQQ is a relatively new nutritional compound first recognized as a cofactor that helps boost the activity of enzymes.2 In humans and animals, PQQ plays many key biological functions, helping with growth factor, newborn survival, reproductive health and more.34
Humans and animals often consume PQQ, since it is found in all plant foods.5 But when PQQ is intentionally removed from the diet in animal research, health problems arise.6 This seems to suggest PQQ might just be a helpful–albeit lesser-known–nutrient for overall health.
BS Alert: PQQ is not “life-sparking stardust.”
Some evidence suggests PQQ is found in interstellar dust, which has compelled imaginative PQQ supplement marketers to claim the nutrient is tied to the first organic materials on Earth, and even sparked the evolution of early life forms.7 To this, we say… come on. Just stop it.
But what about PQQ for the brain?
Recent uses for PQQ target brain health and sharp cognition, where it may have unique nootropic potential. Evidence suggests that, of all PQQ’s beneficial bio-activities, the following may be most well-suited for helping with mental performance:
PQQ plays a vital role in cell-signaling pathways, which allows cells to communicate with each other, monitor the environment, and respond to external stimuli.8
PQQ probably strengthens the brain’s antioxidant defenses:
- PQQ may protect brain cells from oxidative stress, helping to neutralize the cell-damaging, age-accelerating effects of free radicals.9
- PQQ has greater antioxidant potency than vitamins C and E, and is more effective at protecting neurons from superoxides, which are a particularly nasty and destructive class of free radicals.10
- PQQ can also protect lipids or fats from being oxidized, which is important for brain health since the brain is mostly made up of fats.11
It may boost nerve growth factor (NGF). PQQ sparks NGF synthesis, which in turn helps neurons to grow, branch out, and connect. 12 NGF is important in repairing damage caused by stroke, loss of blood flow, or injury. Hence, PQQ has been suggested to have promise in stimulating brain and nerve healing–potentially helping with degenerative neurological concerns.13
PQQ may fight beta-amyloid. PQQ is believed to protect brain cells from beta-amyloid, a protein linked to Alzheimer’s and brain degeneration.14 Some early research suggests that, thanks to PQQ’s apparent regulation of beta-amyloid plaques, fewer brain cells die, production of brain cell-damaging radicals decreases, and brain function is preserved.15
PQQ’s biggest brain buzz: It optimizes brain cells’ mitochondia.
Why do mitochondria matter? Mainly because they generate cellular energy, but also because they maintain cell cycles, regulate cell growth, extend cell longevity, and accelerate cell-to-cell signaling.16
Mitochondrial problems are associated with aging.17 Without PQQ, mitochondria wear out and age faster. In fact, research shows that there is 50% more mitochondrial damage in the brain cells of humans aged 70 and up compared to middle age individuals.18 This mitochondrial damage causes stress to the brain (and whole body!), which in turn consumes even more energy as it tries to stabilize itself. Mitochondria disruption can negatively affect brain function, as well as the function of other high-energy organs.19
Here’s how PQQ might help mitochondria in the brain and body:
- PQQ is believed to shield and protect the mitochondria. This is really just an extension of the compound’s high antioxidant activity.20
- It may boost brain cells’ mitochondrial performance. PQQ may help reverse mitochondrial dysfunction, which in turn may support mental sharpness in times of age-related brain fog.21
- PQQ may multiply mitochondria. Creation of new mitochondria (biogenesis) may benefit longevity, energy utilization, brain health and more. PQQ stimulates mitochondrial biogenesis.22
Mouse Study: Low PQQ intake seems to reduce mitochondria count.
Mice deprived of PQQ showed a 20-30% reduction in the amount of liver mitochondria. These results led researchers to conclude that “dietary PQQ can influence mitochondrial amount and function…” but they also specified this benefit was particular to young mice. 23
How does PQQ feel?
In theory, PQQ might feel like a cognitive power surge. PQQ is strongly associated with healthy, robust mitochondria, which are brain cells’ energy-generating “power plants.” Product marketers say PQQ’s brain energy support may bring “energized” mental clarity: Focus, attention, and quick thinking. Beyond brain energy, PQQ’s antioxidant activity may promote healthy cognition in later years.
PQQ’s bio-activities and mitochondrial support seem fairly well-established… but let’s see if any actual research backs these bio-activities in the context of brain health.
Researchers tested the learning ability and memories of rats using the Morris water maze test, wherein rats were taught to swim from a starting point to a fixed goal for 20 consecutive days. Rats given PQQ showed better learning ability during the early stage of the test. When subjected to oxidative stress, rats fed with PQQ exhibited better memory afterwards.
- Researchers concluded that PQQ’s antioxidant properties are “potentially effective for preventing neurodegeneration caused by oxidative stress,” and clarified that further studies are still needed to determine PQQ’s positive effects on cognition. 24
Using a test called thioflavin-T fluorescence that monitors formation and inhibition of amyloid proteins, researchers confirmed that PQQ can block the formation of prions and beta-amyloids. The latter is responsible for a number of neurodegenerative problems that damage and kill neuron cells.
- Researchers concluded that PQQ “may become a leading anti-neurodegenerative compound in the treatment of neurodegenerative diseases.” 25
There are a few human studies on PQQ, but only two that are related to the brain:
In this double blind, placebo controlled, parallel group comparative study, 71 adults between the ages of 45 and 65 were given 20 mg PQQ, 20 mg PQQ + 300 mg CoQ10, or placebo every day for 12 weeks. They were tested for cognitive function and stress resistance throughout. At the study’s end, the PQQ 20 mg was linked to significant improvements in word memorization (see chart below), recall and some aspects of attention. PQQ did not significantly alter stress resistance, however.
- Researchers concluded that PQQ 20 mg may “improve some high-level cerebral functions including attention and discriminating and processing abilities.” They also noted that benefits seemed to be greater when PQQ was taken with CoQ10 300 mg.26
Researchers selected 17 adult male and female volunteers with a diagnosed sleep disorder or complaint of fatigue to participate in a clinical trial evaluating the effectiveness of PQQ on stress, fatigue, quality of life, and sleep. They were asked to ingest 20 mg of PQQ daily for eight weeks. They were then evaluated using various inventories and questionnaires.
At the study’s conclusion, researchers noted a significant improvement in vigor, fatigue, tension-anxiety, depression, anger-hostility, and confusion following PQQ administration. Quality of life was also evaluated using seven measures—appetite, sleep, obsession, pain, fullness of social life, happiness in family life, and satisfaction in overall daily life—and all of them also indicated significant improvement with PQQ. In addition, two separate testing methods associated PQQ with better sleep patterns.
- The researchers concluded PQQ can become a “useful dietary supplement as it may relate to improving fatigue,” and highlighted PQQ’s ability to improve sleep duration, sleep quality, and overall mood.27 Researchers think PQQ’s antioxidant activity and mitochondrial biogenesis explain the study’s positive outcomes, but also acknowledge that more studies are needed.
- Humans are typically exposed to 100-400 micrograms of PQQ every day.
- Due to a lack of research, optimal daily dosage for PQQ brain benefits are unknown.
- The one small, human, brain-oriented PQQ study found benefits with 20 mg daily.
- Retail PQQ supplements are typically formulated in either 10 mg or 20 mg dosages.
There is no evidence of acute side effects or toxicity for human subjects who were given as much as 60 mg of PQQ per day. The kidney is the principal target organ of PQQ’s acute effects, but only when it is given to rats at a dose of 11-12 mg/kg body weight. It appears to be well-tolerated by humans.
- Pyrroloquinoline quinone (PQQ): Plain, basic PQQ. This is a commodity form found in most supplements.
- BioPQQ™: This is a premium “branded” form of PQQ. It’s more expensive, and found in some high-end brands. We can’t tell how it’s different from plain PQQ, and their website shows no advanced technologies or proprietary processes that would make it different. It does, however, place most of its marketing emphasis on PQQ as a brain health nutrient.
Supplements in Review Recommendation
- BioPQQ, 10 mg
PQQ shows promise for brain health… but keep in mind that evidence is early. The best PQQ research for brain health was funded and conducted by BioPQQ, a company that makes PQQ. Even though BioPQQ is a reputable company, its role in the clinical study may cause some concern. PQQ’s bio-activities might reasonably be expected to help brain health; most likely as an antioxidant for fighting age-related cognitive decline. For overall health, especially heart health, PQQ appears to be more viable as a supplement.
If you want to try PQQ, we suggest a conservative 10 mg dosage. BioPQQ deserves another bump because they are the first (and perhaps only) manufacturer to produce PQQ in accordance with the FDA’s New Dietary Ingredients guidelines. That’s a sign of quality and professionalism, which warrants consideration with a relatively new supplement like PQQ.
- http://www.altmedrev.com/publications/14/3/268.pdf ↩
- http://study.com/academy/lesson/coenzymes-cofactors-prosthetic-groups-function-and-interactions.html ↩
- Steinberg, F, et al. Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets. Exp Biol Med (Maywood) 2003;422:832. ↩
- Steinberg, FM, et al. Dietary pyrroloquinoline quinone: growth and immune response in BALB/c mice. J Nutr 1994;124:744-753. ↩
- Kumazawa, T, et al. Levels of pyrroloquinoline quinone in various foods. Biochem J 1995;307:331-333. ↩
- Stites TE, Mitchell AE, Rucker RB. Physiological importance of quinoenzymes and the O-quinone family of cofactors. J Nutr 2000;130:719-727. ↩
- Kissel, J, et al. Cometary and Interstellar Dust Analyzer at comet 81P/Wild 2. Science 2004;304:1774-1776. ↩
- https://mcb.berkeley.edu/courses/mcb110spring/nogales/mcb110_s2008_4signaling.pdf ↩
- Nunome, K, et al. Pyrroloquinoline Quinone Prevents Oxidative Stress-Induced Neuronal Death Probably through Changes in Oxidative Status of DJ-1. Biol Pharm Bull. 2008 Jul;31(7):1321-6. ↩
- Hara H, Hiramatsu H, Adachi T. Pyrroloquinoline quinone is a potent neuroprotective nutrient against 6-hydroxydopamine-induced neurotoxicity. Neurochem Res. 2007 Mar;32(3):489-95. ↩
- Miyauchi, K, et al. Action of pyrroloquinolinequinol as an antioxidant against lipid peroxidation in solution. Antioxid Redox Signal. 1999 Winter;1(4):547-54. ↩
- Zhou L, Too HP. Mitochondrial localized STAT3 is involved in NGF induced neurite outgrowth. PLoS One. 2011;6(6):e21680. ↩
- Urakami, T, et al. Synthesis of esters of coenzyme PQQ and IPQ, and stimulation of nerve growth factor production. Biofactors. 1995-1996;5(3):139-46. ↩
- Kim, J, et al. The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein. Mol Neurodegener. 2010;5:20. ↩
- Zhang JJ, Zhang RF, Meng XK. Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Neurosci Lett. 2009 Oct 30;464(3):165-9. ↩
- McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006 Jul 25;16(14):R551-60. ↩
- Bliznakov, EG. Aging, mitochondria, and coenzyme Q(10): the neglected relationship. Biochimie. 1999 Dec;81(12):1131-2. ↩
- Mecocci, P, et al. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol. 1993 Oct;34(4):609-16. ↩
- Chowanadisai, W1, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52. ↩
- Tao, R, et al. Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007 Nov 16;363(2):257-62. ↩
- Maruszak A, Zekanowski C. Mitochondrial dysfunction and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Jul 15. ↩
- Chowanadisai W, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52. ↩
- Stites, T, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006 Feb;136(2):390-6. ↩
- Ohwada, K, et al. Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats. J Clin Biochem Nutr. 2008 Jan;42(1):29-34. ↩
- Kim, J, et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion. 2010 Jan-Mar;4(1):26-31. ↩
- Nakano M, et al. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. Food Style. 2009;13(7):50-3. ↩
- Nakano, M, et al. Effects of Oral Supplementation with Pyrroloquinoline Quinone on Stress, Fatigue, and Sleep. Functional Foods in Health and Disease 2012;2(8):307-324. ↩