Mitochondria are the batteries that supply power to your body. As you age, the number and performance of mitochondria you have in your cells decreases, reducing your health and longevity. PQQ (pyrroloquinoline quinone) is one compound, often found in mitochondrial support supplements, that enhances the formation of new mitochondria and increases cellular energy production.

This article will take a deep dive into the beneficial properties of PQQ, before recommending the best PQQ supplements and dosages you should take for optimal health.

What Is PQQ?

Pyrroloquinoline quinone (PQQ) was first discovered as a cofactor for enzyme reactions in bacteria where it serves a similar function to that of B vitamins for humans [1].

A “cofactor” just means that it helps enzymes accomplish their jobs. There is a class of these cofactor molecules that transfer electrons, which is important for our mitochondria to produce energy.

The main cofactors that transfer electrons that you might be aware of are glutathione (NAC increases), CoQ10, FAD, Vitamin C, and NAD. These have different functions in the body, so the effects won’t all be the same.

Importance of PQQ in Humans

Pyrroloquinoline quinone (PQQ) was first isolated in 1979 when it was discovered to be as a cofactor for enzymatic reactions in bacteria [2].

Subsequent research on pigs indicated a similar role in mammals. However, today’s scientific consensus is that, unlike plants and bacteria, PQQ is probably not an enzymatic cofactor in humans [3, 4, 5].

Giving animals a diet deficient in PQQ limits growths and reproduction [6, 7].

Found in high levels in breast milk, PQQ is presumed to be a non-vitamin growth factor. Hence, this is why there is reduced growth in rats deprived of PQQ.

PQQ is found in mammalian tissues. In humans, tissue concentration of PQQ is thought to be around 0.8 – 5.8ng/g [8].

Mechanism of Action

PQQ can bind to proteins in the human body called quinoproteins, and cause biological effects by modifying their activity [9].

It is a remarkably effective antioxidant – around 100 times more effective than vitamin C at quenching free radicals [10, 11].

Enzyme Inhibition

PQQ inhibits thioredoxin reductase 1 (TrxR1), an enzyme that reduces thioredoxin [12].

Inhibition of TrxR1 activity increases Nrf2 activity, ultimately leading to an increase in antioxidant production [13, 14].

Genetic Expression

PQQ depletion affects the way many genes are expressed (2.38% of genes studied) [15].

One key gene affected by PQQ is PGC-1a. By activating PGC-1a, PQQ causes mitochondrial biogenesis (growth of new mitochondria) as well as a host of other beneficial effects [16].

Humans make 100 to 400 nanograms of PQQ each day [11, 17].

The science is not clear how humans synthesize PQQ. In bacteria, PQQ is synthesized from the amino acids L-tyrosine and glutamate [18, 19].



  • The best mitochondrial and energy-boosting supplement
  • Improves cognitive performance
  • Improves mood and mental health
  • Improves sleep
  • Increases wakefulness


  • Good to take a break from it
  • Can be too stimulating for some
  • Possible headache if too much is taken

Health Benefits of PQQ

1) May Decrease Inflammation and Free Radicals

Healthy humans who took 20 mg of PQQ (for a 150-pound male) had a significant decrease in the levels of C-reactive protein (by 45% after 3 weeks) and IL-6. A lower dosage didn’t decrease inflammation [20].

Various urinary markers of oxidative stress also improved, which is consistent with enhanced mitochondria-related functions.

2) Creates New Mitochondria: The Role of PGC-1a

Compounds reported to stimulate mitochondrial biogenesis are linked to many health benefits such as increased longevity, improved energy utilization, and protection from free radicals.

Mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. The creation of new mitochondria by PQQ occurs through the activation of CREB and PGC-1alpha, pathways known to increase mitochondrial biogenesis [21].

As a result of the activation of the PGC-1alpha pathway, PQQ increased NRiF-1 and NRF-2, proteins (transcription factors) that protect us more free radicals by increasing our internal antioxidant production. They also protect us from toxins, UV, etc.

PGC-1a is a “master regulator” that directly stimulates genes that promote mitochondrial and cellular respiration, growth, and proliferation [22].

By increasing cellular metabolism it favorably affects blood pressure, cholesterol, and triglyceride breakdown, and the onset of obesity.

3) May Improve Memory and Reasoning: The Role of CREB

PQQ triggers the DNA reading protein CREB, which plays a key role in growth and gene expression. CREB also stimulates the growth of new mitochondria and increases BDNF [23, 22].

It’s no wonder then that PQQ reverses cognitive impairment caused by chronic oxidative stress in animal models and improves performance on memory tests [24, 25].

4) Improves Brain Function by Increasing Nerve Growth Factor and Schwann Cells

PQQ supplementation stimulates the production and release of nerve growth factors in cells that support neurons in the brain, a possible mechanism for the improvement of memory function it appears to produce in aging humans and rats [26].

PQQ also Increases Schwann cells by increasing the PI3K/Akt signal pathway [27].

5) Is Neuroprotective Against Alzheimer’s, Parkinson’s, and Cognitive Injuries

PQQ is a neuroprotective compound that protects memory and cognition in aging animals and humans, as shown in studies [28].

PQQ increases a protein (DJ-1) that is important to brain health and function. This protein, which increases cell function and survival by combating intensive oxidative stress, is likely important to brain health and function [29].

DJ-1 mutations have been conclusively linked to the onset of rare inherited forms of Parkinson’s disease and other neurological disorders.

PQQ suppresses reactive nitrogen species (iNOS causes this), which spikes in strokes and brain injuries. In this manner, it provides protection against neuro-related injuries [30].

In animal models, administration of PQQ immediately prior to induction of stroke significantly reduced the size of the damaged brain area [31].

PQQ also protects neurons by preventing the long-term overactivation of the NMDA receptors, which results in excitotoxicity. Long-term, overstimulation of neurons is associated with many neurodegenerative diseases and seizures [32, 33].

It also protects the brain against neurotoxicity induced by other powerful toxins, including mercury and oxidopamine, toxins that are suspected to cause Alzheimer’s and Parkinson’s, respectively [34, 35, 36, 37].

PQQ also prevents aggregation of alpha-synuclein and amyloid-beta, proteins associated with Parkinson’s and Alzheimer’s diseases, respectively [38, 39].

It also protects nerve cells from the toxic effects of the proteins that are already there.

6) May Protect The Heart Against Stroke

Administration of PQQ reduces the size of damaged areas in animal models from an acute heart attack.

This occurs irrespective of whether the chemical is given before or after the ischemic event itself, suggesting that administration within the first hours of medical response may offer benefits to heart attack victims [40].

It could be useful to keep this on hand in case loved ones have an incident.

Researchers compared PQQ with the standard post-heart attack clinical treatment (metoprolol, a beta-blocker). Both treatments reduced the size of the damaged areas and protected against heart muscle dysfunction. Only PQQ favorably reduced cellular damage (lipid peroxidation) and the effects were more significant. These results led the researchers to conclude that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage” [41].

Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function [42, 43].

7) Improves Sleep, Mood, and Fatigue

PQQ improves sleep quality and lessens the time it takes to fall asleep.

One open-label human study conducted with 20 mg of PQQ for 8 weeks in 17 persons with fatigue or sleep-impairing disorder noted that PQQ was able to significantly improve sleep quality, with improvements in sleep duration and quality appearing at the first testing period after 4 weeks. It also led to a decrease in the time it took to fall asleep but required 8 weeks to reach significance.

This study also noted improved appetite, obsession, and pain ratings that may have been secondary to improved sleep; contentedness with life trended toward significance over 8 weeks, but results were inconclusive [44].

While this study was done in people with sleep problems, I’ve had similar benefits without sleep issues and others have reported similar subjective experiences.

8) May Decrease Insulin Resistance

PQQ alleviates fat-induced insulin resistance by increasing mitochondrial biogenesis in muscle cells, similar to exercise [45].

PQQ also has some pro-oxidant potential by increasing hydrogen peroxide, but by doing this, it can inhibit an enzyme called PTP1B, which increases insulin sensitivity [46, 47].

Mice lacking the capability of making this protein showed resistance to obesity and were more insulin sensitive.

People with breast cancer have an increased level of this protein [48].

Inhibiting PTP1B also increases the activity of epidermal growth factor.

9) May Help With Obesity

In rats, a deficiency in PQQ reduced their metabolic rate by 10% [49].

Although not studied yet, this could mean that extra PQQ supplementation could increase overall metabolism.

10) May Treat Cancer

In one study, PQQ was toxic to certain leukemia cells [50].

PQQ might reduce the formation of melanoma cancers by reducing melanin-producing protein expression (by inhibiting tyrosinase expression and reducing gene activity) [51].

11) Improves Immune Health

Depriving mice of dietary PPQ caused abnormal immune function, e.g., a dysfunctional immune response to stressors [7, 52].

The addition of PQQ to the diet of mice increased levels of CD8+ cells and lymphocytes (important immune regulators) [53].


PQQ has been shown to bind to uranium [54].

Natural Sources of PQQ

PQQ Foods

PQQ naturally occurs in almost all foods, ranging from 0.19 to 61ng/g, but is especially concentrated in the following foods [8, 55]:

  • Fermented soybean products (e.g. Nattō) [55]
  • Green soybeans [8]
  • Spinach [55]
  • Field mustard (5.54 +/-1.50ng/g fresh weight) [55]
  • Tofu [8]
  • Green tea [8]
  • Green peppers [8]
  • Parsley [8]
  • Kiwi fruits [8]

The PQQ content of even the most PQQ-rich foods is much lower than the amount you can get from a supplement (5 to 20 mg).

Absorption of PQQ

In rats, 62% of PQQ was absorbed in the gut when taken with a meal [56].

In rodents, PQQ is mostly (86%) eliminated 24 hours after ingestion. However, some PQQ residues remain in the skin and kidneys [56].

PQQ is almost entirely metabolized before being eliminated [57].

PQQ Supplement Review

My Experience with PQQ

I first took PQQ when only one company was selling it – life extension, which I believe was 4 years ago. However, I’ve mostly been taking PQQ for the past 2 years on and off, to make way for other experiments. When I was having my high-fat diet meltdown, PQQ and ALCAR were the only things that had a significant impact, offering me:

  • Increased metabolic rate
  • Increased cognitive energy
  • Better memory
  • Better mood
  • Increased metacognition

It also worked through hormesis – worsened performance from 45 minutes to 90 minutes after ingestion, but then increased performance.

Dosage of PQQ

  • A suitable dose for enhancing mitochondria is 0.075 to 0.3mg/kg daily [57]
  • About 20 mg is capable of decreasing inflammation for an average-weight male [20]
  • I recommend to take it every other day or daily if you are trying to correct a problem


A study found that a week’s consumption of up to 0.3mg/kg PQQ (20 mg for a 70 kg male) is perfectly safe [57].

Extremely high IV doses of PQQ (500 to 1,000mg/kg body weight) can cause death in rats [58, 59].

Side Effects of PQQ

Based on these findings, a no-observed-adverse-effect level of 100mg/kg/day was determined for BioPQQ in rats, the highest dose tested in the 13-week study [60].

However, anecdotally, some people have reported mild headaches and insomnia – usually either if too much is taken or if someone is very sensitive to the effects of supplements.

Buy Pyrroloquinoline Quinone Supplements

PQQ Goes Well With 200mg Ubiquinol

Want More Targeted Ways to Enhance Brain Function?

If you’re interested in improving your cognitive function, we recommend checking out SelfDecode’s Limitless Mind DNA Protocol. It gives genetic-based diet, lifestyle and supplement tips that can help improve your cognitive function. The recommendations are personalized based on your genes.

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