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, possibly contributing to the effects of aging. PQQ (pyrroloquinoline quinone) enhances the formation of new mitochondria and increases cellular energy production.

What Is PQQ?

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

Calling something a “cofactor” just means that it helps enzymes accomplish their jobs. There is a class of these cofactor molecules that transfer electrons during reactions; this transfer 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 their effects may overlap but won’t all be the same.

PQQ in Humans

Pyrroloquinoline quinone (PQQ) was first isolated in 1979, when it was discovered to be 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 human 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 [8].

PQQ is found in mammalian tissues. In humans, tissue concentration of PQQ is thought to be around 0.8 – 5.8 ng/g [9].

PQQ was first discovered as an enzymatic cofactor in bacteria. In humans, it appears to function as a non-vitamin growth factor, found in especially high concentrations in breast milk.

Mechanism of Action

PQQ can bind to proteins in the human body called quinoproteins and modify their activity [10].

It is a remarkably effective antioxidant – around 100 times more effective than vitamin C at eliminating free radicals [11, 12].

Enzyme Inhibition

PQQ inhibits thioredoxin reductase 1 (TrxR1), an enzyme that reduces thioredoxin [13].

Inhibition of TrxR1 activity increases Nrf2 activity, ultimately leading to an increase in antioxidant production [14, 15].

Genetic Expression

PQQ depletion affects the way many genes are expressed [16].

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 [17].

Humans make 100 to 400 nanograms of PQQ each day [12, 18].

We do not currently know how humans synthesize PQQ. In bacteria, PQQ is synthesized from the amino acids L-tyrosine and glutamate [19, 20].

PQQ appears to regulate gene expression, though its precise role in humans is unclear.

Snapshot

Proponents:

The best mitochondrial and energy-boosting supplement

Improves cognitive performance

Improves mood and mental health

Improves sleep

Increases wakefulness

Skeptics:

Good to take a break from it

Can be too stimulating for some

Possible headache if too much is taken

Health Benefits of PQQ

PQQ is a natural compound that already exists in our cells, but we don’t yet fully understand how it works, what it’s good for, and whether supplementing it has health benefits. To make matters more complicated, much of PQQ’s mechanism of action has only been studied in animal models, making its role in human health even foggier.

Ultimately, PQQ supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Insufficient Evidence For

The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of PQQ for any of the below-listed uses. Remember to speak with a doctor before taking PQQ, and never use it in place of something your doctor recommends or prescribes.

1) Inflammation and Oxidative Stress

Healthy people 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 [21].

Various urinary markers of oxidative stress also improved, which is consistent with enhanced mitochondrial function.

2) Sleep and Fatigue

PQQ may improve sleep quality and lessen 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 [22].

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 the results were inconclusive [22].

These are very early results in a single very small study. Larger and more robust human trials will be required to confirm PQQ’s role in sleep and fatigue.

In a very small clinical study, PQQ supplementation improved sleep quality and duration as well as other metrics secondary to improved sleep. This study has never been reproduced.

Animal & Cell Studies (Lacking Evidence)

These functions and benefits have been studied in animals or cells, but not yet in humans. As such, we don’t know whether or how much they apply to human health for the time being.

3) New Mitochondria: The Role of PGC-1a

Mitochondrial biogenesis is linked to many health benefits such as reduced inflammation, increased longevity, improved energy utilization, and protection from free radicals [23, 24].

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 [25].

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 [26].

Rodents fed diets lacking PQQ had fewer mitochondria. In cells, PQQ increased transcription factors that activate antioxidant pathways.

4) Memory and Reasoning: The Role of CREB

PQQ may activate a protein called CREB, which plays a key role in growth and gene expression. CREB also stimulates the growth of new mitochondria and increases BDNF [27, 26].

In animal studies, PQQ has reversed cognitive impairment caused by chronic oxidative stress and improved performance on memory tests. This potential benefit has not yet been investigated in humans [28, 29].

5) Brain Function

PQQ supplementation stimulated the production and release of nerve growth factors in cells that support neurons in the brain. This may help explain why increased PQQ is associated with improved measures of cognition and learning in aging humans and rats [30].

PQQ also Increases Schwann cells by increasing the PI3K/Akt signal pathway [31].

6) Neuroprotection

PQQ is a neuroprotective compound that may maintain memory and cognition in aging animals and humans [32].

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 [33].

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, which spikes in strokes and brain injuries. In this manner, it provides protection against neuro-related injuries [34].

In animal models, administration of PQQ immediately prior to induction of stroke significantly reduced the size of the damaged brain area [35].

PQQ also protects neurons by preventing the long-term overactivation of NMDA receptors, which results in excitotoxicity. Long-term, overstimulation of neurons is associated with many neurodegenerative diseases and seizures [36, 37].

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 [38, 39, 40, 41].

PQQ also prevents aggregation of alpha-synuclein and amyloid-beta, proteins associated with Parkinson’s and Alzheimer’s diseases, respectively [42, 43].

The role of PQQ in neuroprotection in humans is not fully understood, and the potential benefit of supplementing with PQQ has not been investigated. Many more clinical trials are needed.

According to animal studies, PQQ may play a role in neuroprotection, memory, and age-related cognitive decline.

7) Heart Health

Administration of PQQ reduced the size of damaged areas in animal models from an acute heart attack. This occurred regardless of whether the chemical was 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; this has not been investigated in humans. [44].

Researchers compared PQQ with the standard post-heart attack clinical treatment (metoprolol, a beta-blocker) in rats. 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,” but this result has not been repeated in humans [45].

Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function [46, 47].

Human trials will be required to determine the role of PQQ in protecting the heart.

PQQ appears to play a role in heart muscle, but it is poorly understood so far. Administering PQQ to animals after a heart attack reduced the amount of tissue damage.

8) Insulin Resistance

According to some researchers, PQQ may alleviate fat-induced insulin resistance by increasing mitochondrial biogenesis in muscle cells, similar to exercise [48].

PQQ may increase hydrogen peroxide, but by doing this, it could inhibit an enzyme called PTP1B and increase insulin sensitivity [49, 50].

Mice lacking the capability to make PTP1B showed resistance to obesity and were more insulin sensitive. Meanwhile, people with breast cancer tend to have an increased level of this protein [51].

Human studies will be required to determine the role of PQQ in insulin sensitivity.

PQQ may alleviate insulin resistance and help resist obesity, but these effects have only been studied and observed in animals.

9) Obesity and Weight Management

Rats deficient in PQQ had a metabolic rate 10% slower than rats with normal PQQ levels [52].

Researchers have suggested that PQQ supplementation has the potential to increase overall metabolic rate, but this potential effect has not yet been investigated in humans.

10) Immune Health

Depriving mice of dietary PPQ caused abnormal immune function and a dysfunctional immune response to stressors [7, 53].

The addition of PQQ to the diet of mice increased levels of CD8+ cells and lymphocytes (important immune regulators) [54].

The connection between PQQ and immunity has not yet been investigated in humans.

Cancer Research

Researchers are currently investigating whether PQQ is worth further study in animal models of leukemia and melanoma [55, 56].

This is extremely early research, and there is no evidence to suggest that taking PQQ supplements prevents or suppresses cancer.

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 [9, 57]:

Fermented soybean products (e.g. Nattō) [57]

Green soybeans [9]

Spinach [57]

Field mustard (5.54 +/-1.50ng/g fresh weight) [57]

Tofu [9]

Green tea [9]

Green peppers [9]

Parsley [9]

Kiwi fruits [9]

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 [58].

In rodents, PQQ is mostly (86%) eliminated 24 hours after ingestion. However, some PQQ residues remain in the skin and kidneys [58].

PQQ is almost entirely metabolized before being eliminated [59].

Dosage of PQQ

Note that the FDA has not approved PQQ for any medical purpose, and there is no safe and effective dose because no studies have been conducted to find one. That being said, clinical research has found benefits associated with the following doses:

A suitable dose for enhancing mitochondria is 0.075 to 0.3mg/kg daily [59]

About 20 mg decreased inflammation in men of average weight [21]

Safety

A study found that a week’s consumption of up to 0.3mg/kg PQQ (20 mg for a 70 kg male) did not produce any adverse side effects [59].

Extremely high IV doses of PQQ (500 to 1,000mg/kg body weight) can cause death in rats [60, 61].

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 [62].

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.